India is the third key pharmaceutical producer in Asia today, after Japan and China with its annual sales of over 16 billion dollars last year. A significant aspect of India's growth story is the fact that it is the only major supplier of quality generics to the US and European markets not China and Japan. Indian pharmaceutical industry exports more than 40 per cent of its production to these and other global destinations. Top Indian pharmaceutical producers like Ranbaxy and Dr.Reddy's earn more than 80 per cent of their sales turnover from exports to the developed markets, while a dozen other companies export more than 50 per cent of their production to overseas markets. A recent Pharmabiz study has concluded that the top 15 Indian pharmaceutical companies account for almost 40 per cent of the country's total pharmaceutical production. Perhaps, the main reason for the record profitability of Indian pharmaceutical sector is its excellent export performance. Growing acceptance of Indian pharmaceutical products in the international market is not just because of its competitive prices, but also on account of the high manufacturing standards in terms of materials used and practices adopted by the Indian companies. Maintaining and improving the quality of pharmaceuticals supplied to the global markets is critical to sustain the export oriented growth of this industry. It is not surprising therefore, India has largest number of US FDA approved drug manufacturing facilities outside the US and the number is growing. Adoption of high manufacturing standards and their periodic upgrading are being carried out voluntarily by these companies to cater to the export markets.
In sharp contrast to this, manufacturing standards for the domestic market are far from satisfactory. Regulatory reforms in a number of other critical areas such as clinical trials, spurious drugs, stem cell research, nanotechnology, pharmaceutical trade, pharmacy education and centralizing drug administration are extremely slow. The central drug authorities had taken more than five years of consultation and debate to bring the basic reform of good manufacturing practices (GMP) to the implementation stage. Although GMP has been made compulsory for the pharmaceutical sector in 2005 by amending the Schedule M of the Drugs & Cosmetics Act, many units are yet to implement the same. This is despite the efforts of the central government to convince small scale pharmaceutical units for several years. Adoption of international standards in drug manufacturing is extremely crucial for the Indian pharmaceutical industry, given its growing exposure in developed markets. The international business of Indian pharma companies is only going to expand dramatically in the years to come considering the intense efforts they are making in these markets. Therefore, a minimum standard in drug manufacturing is more than a necessity. As per the latest figures collected from the state drug control authorities, there is only 5748 drug manufacturing units in the country today. Out of these, only 1,000 units have complied with GMP norms. A large number of remaining pharmaceutical units are also small and are not having adequate financial strength to modernize their plants. A significant outcome of the government decision to implement GMP, however, is that undesirable growth in the number of drug units has come to a halt from last year onwards. Most of the state drug authorities have stopped issuing new drug manufacturing licenses without first establishing facilities specified in Schedule M of the Drugs & Cosmetics Act. Going by the current resistance from the SSIs and lethargy in enforcing Schedule M norms by the state drug authorities, a 100 per cent compliance of GMP norms in Indian pharmaceutical industry should be expected only by 2010.
Rules for clinical research
Clinical research is being projected as a great business opportunity for India by international consultancy companies and country's industry associations for some time now. This has not only attracted a stream of contract research organizations from the US and Europe but has also triggered mushrooming of a large number of local CROs in the country over the years. The shift of clinical trial business to India and some other developing countries from the US and Europe is not without reasons. Increased awareness of the risks involved in testing drugs under development has led to a sharp drop in the number of human volunteers available for this activity. This is despite huge sums of money offered by the MNCs and CROs to the volunteers. At the same, easy availability of human volunteers for trials at far cheaper costs in India is a major attraction. Diversity of India's large patient pool is yet another attraction that pulls MNCs and CROs to this country. Besides all these, there is an overall increase in the number of compounds being tried on humans with the approval process of new molecules by US FDA becoming very stringent since 1996. MNCs like Pfizer, GSK, Novartis and Novo Nordisk have been already conducting human trials for some years in India now. Apart from these, there are a large number of Indian and foreign CROs conducting human trials in India. As there is a perennial urgency to have a favourable trial report, pharma companies and CROs try to manage the same with the support of the medical practitioners. Each clinical trial site is expected to have a functioning ethics committee but it either hardly exists or functions. What is shocking is surreptitious trials being conducted by a large number of small time CROs on illiterate youngsters from slum areas. Unethical and illegal clinical trials are most rampant in the country and are conducted without fear, as there is no law to safeguard the interests of volunteers. There is no system of tracking down these illegal operators and stopping them, as they are operating with the support of certain unscrupulous medical practitioners. The ICMR Ethical Guidelines for Biomedical Research on Human Subjects has been in place as early as 2000. They are not still made into a law. It is high time the government should have made the ICMR's Ethical Guidelines into an Act to commence an effective regulatory monitoring in this segment.
A law for stem cell research
Another emerging front in pharmaceutical research is the application of stem cells for therapeutic purposes. Scientists world over have been exploring the therapeutic opportunities of stem cells for more than a decade now. Private and government laboratories in over a dozen countries, including India have already established stem cell banks. Stem cells are blank cells obtained from human embryos or cord blood, which can develop into a variety of cells in human body.
Scientists believe that these cells can transform into any of human body's approximate 260 different cell types. Blank cells can develop into heart, muscle, brain, skin, bones or to any other body tissues. These diverse cell types could lead to new forms of treatment for many serious diseases that cannot be cured with modern medicines today. No country has, however, developed capability to make this medical technology commercially viable. But some private research institutes and medical practitioners in India have been, of late, claiming magical cures for fatal diseases and publicizing stem cell therapy openly. Laying down a set of rules for this emerging branch of medical research is therefore urgent to prevent its unethical uses. In India, the central government had set up a high level committee to frame a policy for genomic research, including stem cell technology five years ago. A draft guideline for stem cell research was then prepared by Indian Council of Medical Research and it is already there with the government. As per the draft, the Union Health Ministry was to set up a national regulatory system to monitor and sanction stem cell research programme in the country. Half a dozen research institutes are already into serious stem cell research in the country. Formulation of a stem cell policy and enforcement of its rules is therefore extremely urgent to protect the general public from illegitimate uses of stem cells in the country.
Spurious & fake drugs
Manufacture and distribution of fake and spurious drugs have become a major challenge to India's regulatory authorities today. Indian authorities have been battling this menace for some years with not much of a success. The products marketed with brand names of reputed companies with low quality active ingredients or inadequate quantities of ingredients have been seriously hitting the sales of pharmaceutical companies. But what is posing health hazard is the increasing number of products with no active ingredients at all. In India, the central government has been trying hard to find a solution to the problem for more than a decade now. The first serious attempt was in 2003 after several years of deliberations. A bill amending the Drugs & Cosmetics Act incorporating death penalty for offenders was introduced in the parliament in that year but got lapsed with the dissolution of the Lok Sabha soon afterwards. The provision of death penalty was strongly opposed by some political groups, as they felt it can only prolong prosecution process and cannot act as a deterrent. In March 2005, a modified bill with provisions for enhanced prison terms and speedy trials was cleared by the union cabinet. The bill sought to impose a penalty of Rs 1 lakh or three times of the value confiscated goods in spurious drug related cases. The offences under the bill were also made non bailable and cognizable. Another provision in the bill is the designation of one or more session courts as special courts for trial of offences relating to spurious and substandard drugs. Even this bill did not get through the parliament. Now, another attempt is being made by the government to check the problem through the Drugs & Cosmetics Amendment Bill 2007. The bill contains more stringent provisions such as a maximum penalty of life imprisonment and a fine of not less than Rs10 lakh for those engaged in manufacturing spurious and fake drugs. There are also punishments prescribed for the trade. The bill has retained the provision of making the offences cognizable and non bailable. One of the main hurdles faced by most state drug control departments today is the inordinate delay in prosecution of offenders. The provision to have special courts to handle spurious drug cases in the bill could be of great relief for the drug control officials. There are thousands of cases of spurious drugs pending in various state courts. Enactment of the proposed bill without any further delay is extremely urgent to protect the image of the country as a leading pharmaceutical producer.
Irrational combinations
Another area where the central government failed to bring any regulatory discipline is in the area of irrational and harmful combinations of drugs. This is a phenomenon seen mostly in developing countries and India has several thousands of them in the market. Medical experts, world over, have been expressing serious concern over the marketing of increasing number of drug combinations by pharmaceutical companies in the developing countries. They are of the view that a drug combination is technically a new drug entity and its marketing can be allowed only after its safety and efficacy are adequately established. While combining two drugs, the efficacy and bioavailability of the two drugs undergo a change on account of the reactions between these chemicals. For ailments like TB, patients' intake of more than one drug at a time for longer treatment period is a critical factor and drug combinations are justified for the sake of compliance. But, most of the fixed dose combinations currently marketed in India are not rational, as their clinical benefits are in doubt. Some of the widely used irrational combinations in the country are ciprofloxacin with tinidazole, amlodipine with lozarten and nifedipine with atenolol. And there are hundreds of combinations nimesulide with a number of other drugs. Many more such drug combinations are getting approved in various parts of the country and are entering into the market. Manufacturing licenses of these combinations can be obtained anywhere in India as most state drug controllers do not look into safety aspect of these combinations before they issue licenses. Central government has been trying to weed out irrational combinations from the pharmaceutical market for some time now. In November 2001, DCGI first issued a directive to state drug controllers prohibiting them not to issue any more licenses for combination drugs. Nothing happened after this and the state drug control departments just ignored this order. Thereafter, DCGI asked the state drug controllers in July 2004 to withdraw all manufacturing licenses issued by them for drug combinations after May 2002. There has been no follow up action even after this directive. Centre's decision in June this year asking state drug control authorities to withdraw manufacturing licenses of over 1000 fixed dose combinations is yet an another attempt to fix this serious issue. The decision to withdraw licenses issued to irrational combination drugs was taken at a recent meeting of state drug controllers held in Delhi by the DCGI.
The Union health ministry's decision to set up a Central Drug Authority now is with the intention to regularize and tighten the system of drug licensing, which could bring an effective control on fake drugs and marketing of irrational combinations in the country. Currently, DCGI is the authority for approval of new drugs to be marketed in the country but not for issuing manufacturing licenses for pharmaceutical products. Drug manufacturing licenses are issued by drug authorities of any state or union territories. Pharmaceutical companies thus approach the state licensing authorities with some dubious combination of drugs in the name of new products and get approval for marketing. Even if a state drug licensing authority rejects an application for a combination product, the pharma companies do get the approval from another state and market the product all over the country. The reason for uncontrolled growth of undesirable combination products in the market is this. It is extremely important that this practice of irresponsible licensing system should be stopped in a country, which is boasting of supplier of medicines to several developed countries. A bill to bring about this change in the drug administration is now in final stages. This policy initiative should bring in a discipline in issuing product licenses in pharmaceutical sector in the country. A single licensing agency can bring not only more clarity in the system but also some accountability.
Modernising pharma trade
Another area where regulatory reforms are badly required is pharmaceutical trade, particularly the retail pharmacies. They continue to be disorganized and unprofessional. Most of the chemist shops (out of 6 lakhs) spread across the country are being run by traders with no sufficient storage space, no air conditioning and with no presence of pharmacists at the counter. Although these are statutory requirements, very few among the trade follow them. Absence of qualified staff at the pharmacy counters to dispense drugs has been a serious issue the state drug authorities have been unable to enforce for a long time. The centre has taken a serious note of the fact that about 90 per cent of the pharmacies in the country do not have qualified staff at the counters to dispense medicines.
The routine complaint of the traders for not keeping a full time qualified pharmacist at the counter is the high cost of running a trade establishment. And with perpetual shortage of inspection staff, drug control department in most states do not take any timely action against such offences. With substantial growth in demand for pharmaceuticals over the years, the number of pharmacies is multiplying leading to severe competition and unethical practices amongst them. One of the main concerns is pertaining to the delivery of drugs to patients, the primary responsibility of a retail pharmacy. For proper delivery of drugs to patients, advice of a qualified pharmacist is considered necessary. For this, the pharmacist should be equipped with the knowledge of community pharmacy, modern aspects of dispensing, patient counselling, biochemistry and clinical pharmacy and drug store management. But most pharmacies in the country do not have a pharmacist at the counter leading to several unreported dispensing errors.
Organized retail chains like Medicine Shoppe, Apollo Pharmacy and few others have come up in metros and are spreading across the country. Their operations are far better than traditional medical shops but the number of such pharmacies is not very large and one cannot expect any significant growth in the near future. The government is considering a proposal to implement good pharmacy practices (GPP) and a system of accreditation of pharmacies in the country. The move is an important initiative to improve the standards of pharmacy practices in the country. Indian Pharmaceutical Association has rightly taken the first step in this regard with the support of International Pharmaceutical Federation and the World Health Organization. The project will be implemented on a pilot scale initially, with specific guidelines for space, environment, classification of drugs, display of drugs, patient counselling, documentation etc. A joint working committee of stakeholders will be formed to co-ordinate training programmes, implementation and accreditation. The accredited 'Model Pharmacies' will be offered certificates to display a 'quality brand' similar to ISO certification. The project is to be modelled as the GPP programme already being implemented by FIP, WHO and the pharmaceutical industry and trade in Thailand. A change in the mindset of pharma trade is also important to set a trend of transformation of old retail chemist's shops into modern pharmacies in the country.
Upgrading pharmacy education
There has been no serious attempt to modify the curricula of pharmacy education in India despite rapid advances made by the pharmaceutical industry during the last 25 years. Although pharma industry is one of the highly sophisticated industries in India today, manufacturing standards, quality control practices, research activities and clinical practices in this industry have all undergone critical changes during these years. But a fresh graduate coming out of a pharmacy college is largely oblivious of these ground realities as textbooks are outdated and these subjects are not taught. Clinical knowledge is almost totally absent in Indian pharmacy curricula. With growing internationalisation of Indian pharmaceutical industry, the standards of pharmacy education need to be comparable to world class. Pharmacy Council of India had, a few years ago, suggested to abolish diploma courses in pharmacy. This is in line with the internationally accepted norm stipulating a degree in pharmacy as the minimum qualification for being a registered pharmacist. A two-year diploma course is no more considered enough to be a qualified pharmacist in the emerging new era, where pharmacist is expected to play multiple roles. But not much progress has been made so far in this direction, as there is widespread resistance to this move from the pharma trade and managements of colleges running diploma courses. It may take some time to overcome this resistance. But a drastic review of the current syllabus of pharmacy education is urgently called for taking into consideration of the advances made in pharmaceutical manufacturing technologies, clinical practices, community pharmacy concept etc. Majority of pharmacy colleges in the country are also being run without qualified faculty and some of them even do not have competent principals at the top.