India battles quality issues as generic drug demand rises
In what has become an all-too-common headline, an Indian generics manufacturer has had to recall one of its drugs. Zydus Cadila has recalled 10,200 bottles of promethazine hydrochloride, used to treat allergy and as a preoperative sedative. The problem: Atenolol, an antihypertensive, was found in one of the bottles.
Like many other recalls, this is categorized as a class II recall, meaning that while the presence of this drug may cause “medically reversible” adverse events, they will generally not be fatal. Bottling mistakes are one of the leading causes of product recalls---in India and elsewhere, including the United States. However, the frequency of recalls from Indian drug companies, as well as the number of manufacturing facilities that are not complying with cGMP, is alarming.
Last month, Biopharma Dive reported on Sun Pharmaceutical’s recall of close to 430,000 bottles of generic venlafaxine and cetirizine (http://www.biopharmadive.com/news/sun-pharma-faces-another-massive-drug-recall/264115). In fact, Sun Pharma, one of the largest drug manufacturers in India, faced product recalls in March and April as well.
A recall is one thing. However, beyond the fact that seven different Indian companies have issued recalls this year, 33 facilities in India are subject to import bans. That means that no drugs from these facilities can come into the United States until the FDA lifts the ban. It should be noted that 31 facilities in China and eight facilities in Germany are also subject to FDA-imposed import bans. However, the situation with India is more challenging, because India is the epicenter of generic drug manufacturing.
Currently, there are import alerts--products are subject to more scrutiny at the border--- on all four of the lab plants belonging to Ranbaxy Labs, the largest generics manufacturer in India. This is not only bad for business, but unsettling for the patients who depend on generic drugs.
The nuances of Indian patent law
For more than 40 years, India positioned itself to become a major drug manufacturer. However, although it eliminated patents on drugs in 1970---a move that allowed India to develop a very robust generics manufacturing base—the World Trade Organization imposed some intellectual property restrictions through a multinational IP agreement in 1994.
As a result, unfettered patent infringement was not an option, but India chose to limit full patent protection. The Indian Supreme Court does not recognize patents on new uses or formulations of old drugs, unless the formulation is radically different or there is a significant shift in therapeutic efficacy.
Despite the patent-related tension between manufacturers of branded products and Indian generic manufacturers, the demand for generic treatment options is strong. Generic drugs from India play a life-saving role in many situations for the treatment of infectious diseases, as well as heart disease, cancer and other diseases. According to an article published in the Journal of the International AIDS society in 2010, generic drugs from India accounted for more than 80% of the drugs used to treat AIDS patients through donor settings. There is ongoing demand for generic drugs, and any shortages can compromise the well-being of patients who depend on generics.
When FDA Commissioner Margaret Hamburg visited India in February, she discussed the issue of quality control, noting the lack of that control was at odds with patient safety. Now, the FDA is using allocated funds to increase the number of inspections of India’s drug manufacturing facilities. In addition, earlier this month, G.N. Singh, the drug controller general of India, pledged $500 million over a 3-year period to make regulatory improvements.
Regulatory improvements and regulatory oversight will ultimately benefit generic manufacturers, who will not have to face recall situations, alerts and import bans. On the other side of the equation, patients worldwide depend on the availability of generics---and expect these generics to be not only effective, but safe.
- Bristish Medical Journal, bmj.com Production of generic drugs in India
- Reuters India's Zydus Cadila recalls over 10,000 bottles of allergy drug in U.S