Cough syrup deaths: Where is India going wrong with its medicines

This is In Focus, the Hindu's current affairs podcast. Nearly 40 years ago, 14 patients died at Mumbai's JJ Hospital as the medication they took was contaminated with diethylene glycol, an industrial solvent that is toxic to human beings. Over the past few weeks, at least 16 children, a majority of them in Madhya Pradesh and a few in Rajasthan have died, and their deaths are suspected to be because of the same issue, a cough setup given to them for treatment contained diethylene glycol. The issue of medicines being contaminated is not new. How it happens and how it can be stopped are both well known. And yet, India, which accredits itself as the pharmacy of the world, providing generic drugs to many parts of the globe, cannot seem to ensure that medicines for its own children are safe. Despite other issues plaguing the drug regulatory system, why do these deaths continue to take place with little accountability and our cough syrups necessary at all for children? I am Zubeda Hamid, your host for today. We delve into these issues and more with Dr. Anand Fadke, who is with the All India Drug Action Network, a national network that advocates for rational and affordable drug policies in India. Dr, thank you for being here. So let's get started, doctor. The country has been rocked by the tragedy of 14 children dying in Madhya Pradesh allegedly after consuming contaminated cough syrup and at least three other deaths have been reported in Rajasthan that authorities are now investigating. Could you talk to us a little bit about the cough syrup tragedies in India? This is not the first such case to occur, correct? Yeah, there are many, unfortunately. And this is basically because of a chemical called diachylglycol, which is a kind of adulterated substance or when you want to sort of use it as a solvent, many patients require glycerine as a solvent. Now, instead of costly glycerine, some unscrupulous manufacturers use the solvent which contains diachylglycol in small amounts. Sometimes the amount is big and therefore sometimes there is acute kidney injury because of the ethylene glycol. So this is the basic problem and therefore, since the pharmacoregulatory control is very poor in India, this has been happening repeatedly. Way back in 1986 in Mumbai, what we call the Jeje Hospital tragedy, this ethylene glycols was was responsible for a number of deaths after which a Lentine Commission, I hope you have heard about it. It is a famous Lentine Commission who was set up, which made a whole range of recommendations so that such tragedy does not occur again, but these recommendations have not been followed properly. We will come to that, but this is dates dates back from 1986. So this, as you said, is not a new problem. This has been happening for decades now and the same problem continues to occur. Am I right? The same diethylene glycol is the, during the manufacturing process, the syrup gets contaminated with this, correct? Yes. So the essential problem is, substandard cheap raw material is procured by unscrupulous manufacturers and this leads to contamination of the syrup. Could you tell us a little bit about diethylene glycol? What does it do to the human body? As I said, it causes kidney injury, chronic renal failure. So the children die of kidney problems? Anybody, whether adult or children, if they consume, they are forced to consume diethylene glycol. They will develop renal toxicity and renal failure. So tell us a little bit now about the commission and its guidelines and why even though this problem has been known for now close to 40 years, nothing much has been done about it in terms of regulatory oversight. See, after the Lentine Commission has a follow-up action, you must have heard about Raghunath Mashalkar committee, which was set up to give comprehensive recommendations because the Lentine Commission was a legal authority, didn't have an idea about what steps to take to prevent these tragedies. So this Mashalkar committee was appointed and it made a series of recommendations. And unfortunately, many of these recommendations have not been followed. I will give you just one example. What Mashalkar committee in 2004 has recommended was that there should be one drug inspector for every 50, 50 manufacturers and one drug inspector for 200 chemist shops. And this ratio has never been achieved. Even in Maharashtra, which is supposed to be a progressive state, there are 200 posts of drug inspectors which are created, but only 48 are currently employed. So these vacant posts are there and this was the norm was set up way back in 2010. But now with the increase in population and more so in number of drug manufacturers as well as chemist shops. So if you take the current figures of the number of chemist shops in Maharashtra as well as number of manufacturers, pharma manufacturers, you require a 500 drug inspectors. We have only 48 in place. So you can imagine the absolutely torn or, you know, unformed drug-regulated system in even a state like Maharashtra. So this is very tragic. And unless there is a public outcry and continuous pressure, I don't think things will change. So doctor, does that mean that most pharmaceutical companies in India function without any regulatory oversight at all? Can you tell us a little bit about the schedule M guidelines that the government has brought in? The pharma regulatory system in India operates at the state level. The central level of pharma regulatory system is responsible for giving or not giving permission to manufacture and sell medicines. But actual oversight of the manufacturing unit is left to the state. It is up to the state to give permission for a pharma company to begin operations or not. So basically, it is the state FDA which is responsible for actual implementation of all the laws, regulations, which are sort of laid down in the drugs and cosmetic act. Now on drugs and cosmetic act lays down section called schedule M, which basically means if you want to start a pharma manufacturing unit, what are the basic requirement that you must comply with? And basically it means how much of area you should have, what is the level of cleanliness, what kind of machinery, what is your quality control, what is your follow up, etc., etc. And all this has to be followed. If you follow all that, schedule M, which is a very detailed schedule, generally the quality of the medicines would be taken care of. Unfortunately, out of 10,500 manufacturing units, pharma units in India, only 20% are fully compliant, 30% are half compliant and 50% have absolutely no compliance at all. So more than half of our pharma industry is not as per the schedule M and therefore it is no surprising that we keep getting substandard medicines. Now many other substandard medicines go unnoticed because supposing you get a painkiller, the painkiller may not be very effective. But since it is somewhat effective anyway, pain decreases over a period of time. It is not very easy to detect that you are getting less than optimum results. It is very difficult in many other medicines, many times the diagnosis is also not correct. These are more complex problems but the point is more than half of our manufacturing units do not go by the mandatory schedule M, which is the government has made it no mandatory. That is very tragic indeed. And yet India positions itself as the pharma capital of the world, as like one of the world's biggest suppliers of generic medicines. Is that correct? Yeah, but what is happening when we export to especially developed countries, they accept medicines only which will pass their stringent quality control test. So these units which export medicine, they are actually at good quality production. So it is not that Indian pharma industry does not have the capacity. But depending upon the regulatory strictness, their behavior changes. In many cases, and I am not saying everybody, but this is what is happening. And therefore, like for example, we out of our total exports, half exports go to the United States. And the US Medicare program, which is basically generic based on generic medicines is to substantial extent depends upon the Indian pharma supplies. But all these exports are monitored. Not only that, the Food and Drug Administration, FDA of US actually has monitored some of our manufacturing units. So we have certain manufacturing units which are exclusively meant for export to US. And these manufacturing units, those pharma companies allow US FDA guys to come here and sort of follow all their guidelines, all their requirements. And therefore, all these exports to Europe or any other developed country are up to the mark. Whereas for domestic market, the same companies have double standards. Many of them, I am not saying everybody. And we get substandard many times for Indian consumers. So as you said, double standards, one standard for the West which has stringent regulations and one standard for us because we do not bother to regulate them as well. So as you were telling us, Dr. Fadke, this is a state level issue in the sense that it is up to the states to regulate the companies that are operating in their jurisdictions, correct? Yes. So what is going around? One problem you pointed to was purely a lack of human resources. We just do not have the enough number of drug inspectors to check. What are the other gaps in the system? Secondly, like all other government machineries, it is non-transparent and corrupt. So many of the drug inspectors, whosoever are there, they, many of them just collect hapta and give OK to the farm units which pays them all right. So and then the records are not good. And therefore, and there is no chance for civil society people to sort of monitor this like our advocacy groups, we do not have any access to the reports and to sort of cross shake what these guys are doing. So it's all a close circuit, corrupt, inefficient, incompetent mechanism. But since these manufacturers are allowed to send their medicines all over the country, for instance, a Tamil Nadu pharma company can send its medicines to Rajasthan and Madhya Pradesh, is there a need for a central framework in order to regulate this? Not sure about it. I am personally confused about it because we are basically a federal structure. Therefore, if you basically, I suppose the manufacturing Maharashtra is well controlled, then that manufacturer can send medicines anywhere in India to Kashmir or to Tamil Nadu. But then the manufacturing unit shifts to Tamil Nadu or Kashmir, there, of course, that local unit has to, the local authority has to take care that there is no substandard production. You should know, I mean, I have already mentioned that the consent or the permission for manufacturing is given by the center. So once you get the permission, like this is what is happening. Supposing in Tamil Nadu, for example, where the system is worse, comparatively much better. If the drug inspectors are sort of start questioning the manufacturer about a number of things, they simply shift it to place like Himachal Pradesh, which is hardly any pharma regulation. So this is also problematic. So I am not very sure whether centralization will help. I think the basic problem is number one gross deficiency in human power in terms of capacity and secondly, non-transparent corrupt practices. So whether central or state level control, I think this central issue has to be sort of resolved. Dr. one thing that has got the Indian Medical Association up in arms since yesterday has been the arrest of the doctor in the Madhya Pradesh case. Now the doctors associations are pointing out that he had no way of knowing that it was a contaminated cough syrup when he prescribed it. Where do you think the responsibility should lie? Should it be with the manufacturer and the state rather than the doctor who actually prescribed the drug? Absolutely. It has to be with the manufacturers. But the doctor doesn't have an idea of whatever the FDA has permitted. As a doctor, I have to assume that whichever prescription that I give will have a standard quality. I have zero control over it. So I think absolutely nonsensical and very deplorable that doctors were arrested. This is simply wrong. Some kind of scapegoat. Now doctor, let's move on to the other half of what we've been discussing. We've for so long looked at the manufacturing process, how it gets contaminated and what the gaps in the system are. But the next part can deal with do we actually need cough syrups for children at all? Since oral physiology of children is relatively not completely mature, even up to let's say two to four years and therefore any medicine of whatever nature has to be given very, very cautiously. And therefore, medicines have to be given much more cautiously in small kids compared to adults. And therefore as far as possible, I think all medicines should be only strictly controlled and strictly effective, known effective medicines needs to be given to the children. Especially this cough and cold medicines. As you probably know that cough and cold, most of it is because of viruses or because of allergic reaction to surrounding. And therefore there is no cure for it. There is no definitive remedy for it and they tend to sort of subset on their own. And therefore your sort of aim is to give symptomatic relief. And a simple measures like sort of having a sip of warm water, comfort, etcetera, etcetera. And of course, paracetamol, all these things are generally all that you need to do in a case simple case of cold and cough. But you can, if you really want, can judiciously use some kind of a cough suppression in a small child, but that has to be a very weighty decision. And therefore, it is certainly not in favor of pediatric cough syrups at all. What is available in the Indian market in terms of pediatric cough syrups? Are they rational use drugs? And if not, should all of, should most of them be taken off the market? I think most of them need to be taken out of market. There hardly anything which can be, we can say rational. As I said, there are exceptions, but whichever one comes across, almost all of them are certainly problematic for children, especially below two and four years of age. Now, if a six-year-old child who keeps having a very persistent drag cough, you know, which is very troublesome, which you cannot, the child is not able to sleep at night, then you can give some symptomatic relief with some kind of a cough suppression. But especially small children, yes, it is very problematic to liberally used cough mixtures, and therefore, they are simply not advised. Tell us a little bit about the ingredients. You are saying that these are irrational combinations. What goes into the cough syrups? Many of the cough syrups contain an anti-stamina, which is basically anti-allergic medicine. This assumes that your cough cold is because of allergy, and many times the cold is because of virus. So, when the cold or cough is because of virus, if you give an anti-stamina, which is anti-allergic medicine, that is not rational. And even if there is an allergy, you give anti-allergic, there are side effects also. Like an anti-allergic medicine tends to make your nose and throat dry, and therefore, you might, your nose may become dry, but you, there will be itching inside. So, you have to carefully weigh the side effects versus the positive effect and avoid as far as possible these medicines. But I am not in favor of ban as such. I mean, there is no medicine which is given only up to two years of old. Cough syrup is a cough syrup with pediatric dosage forms. So, a bottle of cough syrup with pediatric dosage forms can be used for a two-year child or with a higher dosage can be used for an eight-year old child also. So, there is no point in banning a rational cough syrup. But most cough syrups are irrational, and therefore, I just keep repeating that we have to be very judicious and careful in using those in children. Do you think that there is a huge need for education both amongst the parent community, the regular citizens of our country, as well as the medical profession? Because in a lot of cases, doctors say that parents are asking for it, and if it is not prescribed, they go to a pharmacy and buy it anyway. So, there are certain parents of that kind, but if the doctor is carefully up and bothered enough, it is possible to explain to even less literate people that this medicine, this can be of some help, but it can cause troublesome side effects and are even dangerous. So, I would not advise you. So, the point is the doctor has to spend time. The doctor himself or herself has to be actually convinced about it and should be knowledgeable about it. And unfortunately, in India, half the general practitioners are non-allopathic doctors, Ayurveda and Humbhvidhik doctors, they know nothing about allopathic. And therefore, they just listen to the pharma companies and prescribe medicines. Even the MBS ones, many of them have not undergone retraining or forgotten their science, and the pharma companies keep sort of sending you promotional material, they indirectly try to bribe doctors also, sometimes directly bribe. And therefore, ignorance and commercial interest. These are the things which prevent many doctors or large-injured doctors from educating the people. There are, of course, good examples and there are good pediatrician, good doctors who explain to the patients or reassure the patients, give them alternative. And secondly, the over-the-counter cough syrups, which are advertised in the lay media, so people do not go to the doctors at all, they are influenced by the lay media exposure and of course, you want relief from the child. And as I said, sometimes you do get a relief even with an irrational cough syrup. Like if you give an anti-stamina, the nose will dry up and you will feel that the child is better, sometimes the child is better also. So I do not think there are any iron laws, it all depends upon weighing the child, the child's history, overall health, certain conditions and efficacy and side effects of particular medicine. All this needs to be judged together. Education of patients is important. The first thing to do, mal-education has to stop. Wrong advertisements of cough syrups, in fact all advertisements of cough syrups should be stopped. So overall concluding, doctor, would you say that A, stop the irrational combination of drugs overall, B, doctor education and patient education and C, stop the over-the-counter sales of cough medications? Yes, yes. Anything else doctor? And also there is one economic factor to it also. I mean go to a doctor, pay doctor's fees and get the medicine, spending time and money. So people sort of try to make a shortcut and directly go to a chemist shop and they know anyway it is not a very serious problem, it is troublesome. So they will ask for actually chemist advice, the chemist act as doctors and people are happy about it because they want to save money. So even if they have sort of a well-being of their children at heart, economic factors and convenience also forces them to go to chemists and seek medicines without doctors prescription. So there can be some medicines as we call OTC, I am not against OTC as such. But there has to be a strict list of medicines which are relatively very safe and effective and these are the only ones which should be available over the counter or should be advertised in the lay media. This is not happening in India, you can buy anything on your pharmacy shop from any powerful antibiotic to anything and that is a big tragedy of the Indian pharma business. Last question doctor, what do you tell parents of small children who have a cough, do not give anything? Not a very easy question to answer because there are no easy answers, please look for a good doctor, a qualified doctor, this is not very practicable in rural areas and do not sort of go for very convenient and quick solutions if the doctor has warned you to be aware of the side effects or so I would generally say as much less medicines as possible without medical advice, please don't indulge in self-medication for your kids. Thank you so much for speaking to us today, Dr. Fadke. Thank you.