Pharmaceuticals, Yesterday, Today and Tomorrow
I wish to thank the States Pharmaceutical Corporation management for giving me this opportunity to voice my thoughts on the pharmaceutical industry in Sri Lanka. May i dedicate my presentation to one of our great Lankaputhra, a true human being who tried to bring back humaneness to humanity in the best way he knew. Dr. Senaka Bibile.
In the latter half of the 20th century the World Health Organization launched a very ambitious project, HFA-2000, Health For All by 2000. Despite all obstacles, had the WHO been able to achieve it, we would not be here today, because there would not have been any need for drugs. It could also happen if someday we can all accept the Zero Option and say No to Drugs.
Some of you would be familiar with the old Persian saying, "forego wealth for health, health for knowledge and distribute knowledge for true faith". If we have true faith in whatever we believe in, if we have the knowledge, then health and wealth will anyway be with us, without any special effort towards achieving them.
Medicine around the world goes back to pre-historic times. The oldest evidence is available from the study of the 5300 year old 'Iceman' found in the Italian Alps in 1991. He had in his pouch a lump of bracket fungus, Piptoporus betulinus, a mushroom which contained an acid which was laxative, and a resin that was toxic to bacteria and intestinal parasites. This showed that either the man himself could diagnose his illness, and knew how to treat it, or there was a medicine man or woman in his village who had prescribed the treatment.
Healthcare in our country too goes back many thousand years to the time of Ravana who was a great physician and had written several books on healthcare. This is not the Ravana created by Valmiki.
Dr. John Atygalle, Colonial Surgeon, in his Sinhalese Materia Medica written in 1917, comments on the medical miracles described in the 13th century chronicle, Culavamsa, about a cephalotomy by King Buddhadasa, for the removal of a hydatid tumour from a man's brain.He had also straightened out the back of a bhikkhu, who had been bent in half. He had once opened up a belly of a naga, with a knife he carried in his belt, removed an affected part, and treated with some herbs. Though it is normally accepted that the naga meant a snake, probably he was a man of the Naga tribe. The Pujawaliya, written in 1266, by a physician-monk, mentions an epidemic 'Rakthakshi Maraka Jwara Rogaya'. King Siri Sanghabodi had performed Satyakriya and was able to drive away the yaksha who caused it. Prof. Kumaradasa Jayasuriya had considered this could have been leptospirosis. Whatever it was, we had faced a serious epidemic and had been able to eradicate it.
In our literature we find many references to healthcare which display the awareness among the people of common treatment methods. Sadharmaratmavaliya mentions Avasta piliyam first aid. Treatment was known for hemorrohoids, filaria and leprosy. There were references to contraceptive drugs Vanda behet, and fertility drugs. Family planning would have been in practice.
The importance of taking good care of one's health is seen well in the precautions taken like gaba pirimesima or gaba raksanaya, during pregnancy. The Butsarana mentions that a mother would take medicine herself when her baby was sick.
Our ancient healers could diagnose and treat 76 different ailments of the eye, without the aid of any electronic or digital equipment. The Sivi Jataka even mentions the transplant of an eye. The bark of the Kumbuk tree, Terminalia arjuna, had been used in the treatment of Cadiomyopathy, which also means the disease could be diagnosed by our physicians.
When we talk of healthcare in Sri Lanka we have to look at the role played by Buddhist beliefs and rituals. The WHO definition today comes close to the Buddhist concept, “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”.
Whatever the ailment was, one of the major ingredients always found in our medicine was 'Loving Kindness'. The days are gone when a mother would prepare the coriander water by herself, hand it to the child and stroke his head as he drank it, telling him that with this drink the cold will be gone. Today we only remind our children to take the tablets or capsules. Coriander seed oil is one of the 20 major essential oils in the world market and it has been confirmed that it is effective against both Gram-positive and Gram-negative bacteria and as a diuretic.
SPC can import all the drugs, and distribute them. But without the other ingredients, the loving kindness of the doctors, nursing staff and the family, the effect of the drugs would be minimal.
In the Anguttara Nikaya, Gilana Sutta, we read about three types of sick people. Some people require Medicine, food and nursing, others recover with or without one or two of these requirements, while others without any of them.
The role of SPC is to provide one of these requirements, the medicine, because most of us belong to the first category. This medicine should always be of the best quality, and yet affordable to every Sri Lankan, and not just the privileged few. Such quality, affordable medicine should always be available, both in our state hospitals and in the private pharmacies, without any shortage.
I recall the times when we did not hear of any drug shortages in the country, in our hospitals. There was hardly any emergency purchasing. All DHS tenders were announced and closed within the first few months of the year, with expected deliveries in January and June of the following year. There was always sufficient stocks of most of the drugs with long shelf life. This system helped in planning, budgeting and storage for the SPC and MSD, while it also helped the manufacturers, for they could plan their production and shipments and work out the costings accordingly. Even SPC tenders were very regular, and the tenderers were able to plan their productions accordingly.
Our government could also look into the possibility of controlling the prices of branded drugs, the way UK and Germany are trying to do, using value-based pricing. UK authorities recently decided the benefits of a new cancer drug did not outweigh the high price.
We could look forward to the day when SPC would move on to on-line tenders, so the bidders could submit their offers and follow-up on the evaluation and award and the shipments, which could make everything more transparent, would expedite the process and ensure continuous uninterrupted supply of the drugs. The process would also be more transparent, with most of the data available in the public domain.
On-line registration of drugs is also an urgent need, with CDDA, NDQAL, MSD and SPC all in one network.
When we talk about affordable prices, one important observation made is that the prices of almost all drugs kept coming down every year. This is one good factor with tenders, and the healthy competition generated by it.
That is where the quality should override the price. The consumer today is in a position to pick and choose, to select the best product at the best price. Thankfully now the SPC is insisting on pre-shipment samples, and perhaps they should also insist on the sources of the ingredients and the date of manufacture of the ingredients.
Patents and copyrights have become almost indispensable. But such protections often do not benefit the consumer, and there is always exploitation of the traditional medical systems and medical knowledge, and the exploitation of indigenous herbs in the developing countries. One example is turmeric (Curcuma longa). In 1995 US granted a patent but when India established that it had been used for thousands of years the patent was revoked. The Indian government had to fight again a new patent application in the United States, a few months ago, for Turmeric, Apple and Tulsi for treatment of inflammation, psoriasis and gastritis.
Indian scientists at the Tropical Botanical Garden and Research Institute developed a sports drug using the Traditional Knowledge they obtained from the Kani tribe in Thiruvananthapuram, South India. The scientists isolated 12 active chemical compounds from the plant Arogyapaacha, (Trichopus zeylanicus travancoricus, what is called Bim Pol in our country) to develop the drug with a brand name Jeevani. The technology was sold to a commercial organization. As the Hindu reported on Oct. 8, 2012, "The benefit sharing is a shambles, ....all that is left for the Kani tribe is an unfinished computer training center."
Recently the US FDA has started Break-through drug approvals, specially for oncology drugs. It may be done all with good intentions, but if we cut down on the standard phase II and III procedures, could it not mean we will be using innocent patients as guinea-pigs? In 2012 US FDA has approved 39 New Molecular Entities. All of them would be patented drugs, which will be beyond the reach of about 80 percent of the people around the world. Yet they will bring in immense profits, or these companies would not invest over one billion dollars for each new drug. These companies have to recover not only the investment for these drugs, but all the investments on other R&D projects which fail along the line, specially which fail the trials in Phase II (with a 22% success rate) and III (65%). Then there is also the loss of revenue from the earlier drugs where patents have expired. EvaluatePharma forecasts that $ 290 billion in sales are at risk from patent expirations between 2012 and 2018.
Pfizer lost the Viagra patent in Europe yesterday, and there are 20 generics waiting. But last year viagra sales topped $ 2 billion.
FDA is not god. They are not infallible. There were many occasions when after approval of a drug, they had to withdraw it.
Just a week ago FDA had announced setting up of a new study to look into two diabetes drugs by two giants of the pharma industry, because of reports of possible pancreatic cell growth that could turn cancerous. It is the FDA who had approved these drugs originally and one of the drugs had earned $ 4.1 billion last year from its sales.
WHO has also set up guidelines for bio-similar products, where the generic is compared with an "innovator" product. But one such product is under investigations for its safety, and the innovator had up to last year paid $ 780 million in legal settlements. If the drug was so safe why did they pay that?
Are all these NMEs really necessary? Shouldn't the FDA consider if an NME had any reasonable benefits over the existing drugs. Because among the 39 NMEs approved by FDA last year there is a new erectile dysfunction drug (Strendra) and one for weight loss (Belviq).
The race for developing more new drugs means more clinical trials. Times of India reported on August 18th, 2012, that 211 people had died in the past six months due to serious adverse events during clinical trials carried out by the drug industry, and in 2010 the total number of deaths was 668 (2 more than the number of the beast). In 2008, in one trial 49 children had died.
Then there is corruption. In 2011, a leading drug maker was indicted for alleged bribery in an East European country. During the same year another giant had agreed to pay $ 7.9 million to end a probe of bribing officials in a European country, and to pay another $ 70 million in a settlement related to Foreign Corrupt Practices Act.
Often every good thing is exploited by man. Fortunately for Sri Lanka, all ethical drugs, approved and registered by the Drugs Authority are free of all import duties. This is a real blessing for our people. Our government is able to keep drugs on duty free lists because there is no need for protecting a local industry. Pharmaceutical manufacture in our country has not been viable for the private sector. If we are to manufacture any drugs we have to import not just the APIs and the excipients but the empty capsules, vials, bottles, even the paper and the ink for printing the cartons and labels.
Yet the State Pharmaceutical Manufacturing Corporation is doing an admirable job in contributing to the SPC's attempts to provide quality drugs at affordable prices.
SPC at present is the only importer who checks pre-shipment samples of their imports. For drug imports by the private sector there are no quality checks at the time of imports. Once a drug is registered with the CDDA, for the next five years, the only quality controls are the random checks by the Drug inspectors. Manufacturers are free to use any raw materials, any APIs of any quality, once the drug is registered.
Even for the import of cement, the shipments are released only after samples are tested by the Sri Lanka Standards Institute. But any registered drug can be imported, simply on the Certificate of Analysis from the manufacturer. Fortunately for vaccines, at least there is the requirement of a Lot Release Certificate from the country of manufacture. One problem we could face in quality checks of imported drugs is that our country may not have the facilities to test all the drugs imported. In such cases, perhaps we could negotiate with the Health departments in the countries of manufacture to provide a certificate which would be less expensive and more reliable, because any testing by private laboratories overseas could only add to the cost of the drug.
We are all very proud to always claim our drugs conform to all requirements of quality, efficacy and safety. But I have always believed that we should also satisfy our own conscience, specially about safety and efficacy. The drugs we manufacture, distribute and market should be only drugs which we have the confidence to give to our own children.
When it comes to quality issues and human or machine errors, not only the small time generic manufacturer, even the big names could fail. A man died in France recently, because the manufacturer had packed Zopiclone in a carton labelled Furosemide, and 190,000 boxes had to be withdrawn from the market.
Pharmaceuticals are not just a commodity, even though in the open market economy today even life saving drugs have been commodified. In our country we have a saying, Hamba karanava and hari Hamba karanava. That there is a difference between earning, and rightful earning. Pharmaceutical business should always be limited to rightful earning.
The business of ill-health also rides on the proliferation of WMDs. Weapons of Mass Destruction. I don't mean Nuclear weapons, but the chemical and biological weapons used legally and often subsidized by governments, in day to day life. They are the agrochemicals, and genetically modified plants and animals. They cause most of the diseases today, and in years to come for our future generations. Unfortunately, some pharmaceutical companies also produce these WMDs and or are riding piggy back on them. We already have a serious epidemic of CKD in the rice producing regions due to use of agrochemicals.
There are two more WMDs legally manufactured, sold and consumed, which are harmful not only to the health of those who consume them but to their families and the society. We only talk about these two WMDs just on two days of the year. October 2nd against alcohol and May 31st against tobacco. Yet tobacco continues to kill 5 million human beings every year and 100 million suffer at least from one tobacco related illness. By 2030 the death toll will go up to 8 million. Alcohol causes 2.5 million deaths. WHO reports that 9% of deaths among the age group 15 - 29 are alcohol related.
If all governments around the world could ban both alcohol and tobacco, we could reduce this death and suffering drastically. Shouldn't this be a part of our preventive healthcare campaign?
One more product which helps us commit slow suicide is the sugar substitute. A study last year has confirmed that Aspartame is linked to Leukemia and Lymphoma, while the European Food Safety Authority reports "The body may sometimes convert aspartic acid into the neurotransmitter glutamate which can have neurotoxic effects." Another more recent sugar substitute is Sucralose, approved by FDA and used even in our country. It was a product that was accidentally discovered when developing a new insecticide. It is a Chlorocarbon, like DDT, but FDA has not conducted toxicity tests on it. This is all good news for some Pharma manufacturers, because when food manufactures add carcinogens and other toxins into the food, people get sick and need drugs.
Here too is a contradiction. FDA has not yet approved the natural sweetener extracted from the plant Stevia rebaudiana because they have concerns over the effect on kidneys, cardiovascular and reproductive systems!
Another threat to the world, to mankind and all life on Mother Earth, is the indiscriminate discharge of harmful effluents by the pharmaceutical industry too. Pollution in all forms is a major threat to health all over the world. Most of you here who are from India would have seen or heard of the plight of the Yamuna river, how the people in Agra do not use the water from the city supply even for bathing, because it is so contaminated. They are even worried about the foundation of the Taj Mahal.
Such pollution of our water we drink, the air we breath and the food we eat is causing most of the illness, and that is why we need drugs and drug manufacturers and distributors, who in turn contributed to pollution too.
We now talk of e-waste, of electronic equipment and consumables yet ignoring the d-waste, digital waste, all the garbage we are piling up as unwanted software and documents. P-waste, or pharmaceutical waste has been with us even longer.
The Cary Institute of Ecosystem Studies, in New York carried out a research recently on water samples of biofilm from streams in Maryland, New York and Indiana, in which they found antibiotics, analgesics, antehistamines and even caffeine. It would be the same the world over. A study by the United States Geological Survey published in 2002, found measurable concentrations of prescription and nonprescription drugs, steroids, reproductive hormones and their by-products in 139 streams across 30 states.
We all of us, manufacturers, distributors and consumers are all responsible for pollution by pharmaceuticals. In addition to the effluents from the factories, there is effluent from hospitals, and from warehouses. How do we dispose of expired drugs, or in case of quality failure? Where does all these chemicals end up? And where does the residual drugs from excretions end up? A study in 2005 reported that 90% of the anti-seizure drug Pregabalin, 90% of Metformin and 75% of Lisinopril is excreted.
Even WHO guidelines sometimes could misguide people. In the WHO guidelines for disposal of drugs, they say, "most pharmaceuticals are relatively harmless to the environment; they do not present a serious threat to the public or environment unless handled recklessly". No environmentalist with an independent mind would agree with this statement. WHO takes this insult to mother earth further, by saying "syrups and IV fluids can be diluted and flushed into sewers... fast flowing watercourses may likewise be used to flush small quantities of well-diluted liquid pharmaceuticals or antiseptics". What is a small quantity?
We as human beings, have a collective responsibility to prevent such pollution, and formulate fresh guidelines for disposal based on the latest pollution studies.
Let us all get together to build a healthier nation, a healthier world, and let us bequeath our future generations a greener Mother earth, free of pain and suffering. Let us bequeath them a world where they would not be dependent on drugs (both narcotic and medicinal).
(my speech delivered at the State Pharmaceuticals Corporation, Sri Lanka, Suppliers Conventionm 2013, June 22nd, 2013 at Cinnamon Bey)