Pharmaceutical Policy and Access to Essential Medicines - Kolkata Declaration

The National Seminar on Pharmaceutical Policy and Access to Essential Medicines organised by Jan Swasthya Abhiyan, Federation of Medical and Sales Representatives’ Associations of India, National Campaign Committee for Drug Policy and All India Drug Action Network and supported by the World Health Organisation, India country office discussed different aspects of the country’s pharmaceutical policy. The seminar was attended by one hundred and twenty eight activists, academics and experts from all parts of the country that deliberated on different issues related to the pharmaceutical sector in India.

The Seminar noted that the country’s record in controlling diseases that affect large sections of the people has been far less than satisfactory. The country faces new challenges in the form of increased incidence of “lifestyle” diseases and infections such as HIV-AIDS. This ominous situation admitted in the National Health Policy-2002 needs to be addressed seriously. Disease pattern and common ailments highlighted in NFHS-2 survey should also be taken in consideration.

The seminar also noted the new situation created by the policy of globalisation, privatisation, liberalization and the new product patent regime which together have threatened the national self reliance as well as availability and affordability of essential medicines. The seminar felt concerned about the worsening situation on the drug price front with its disastrous impact on the poor. With this back ground the seminar expressed the need to formulate a National Pharmaceutical Policy that addresses the critical issue of universal access to essential medicines and of national self-reliance. This policy should be prepared by an intersectoral committee of the Ministry of Health & Family Welfare and Ministry of Chemicals & Fertilizers after discussions with all sections that have a stake in the pharmaceutical sector. The two should jointly constitute a National Drugs and Therapeutic Authority, which should be a statutory body with powers to regulate all aspects of the National Pharmaceutical Policy. Apart from experts, this body should also include representatives from health movements.

Given the above the Seminar resolves the following suggestions be considered while making the National Pharmaceutical Policy.

National Essential Medicines List

The Govt., based on epidemiological data, should update the National Essential Medicines List (NEML) and also prepare a Graded Essential Medicines List that is appropriate for each level of the health care system. The National List needs to be adopted by different states and adapted by them based on local conditions and disease profile.

The Govt. should monitor and ensure the availability of Medicines listed in the EML. Production of these medicines from the basic stages should be ensured through production control mechanisms.

 It should be made mandatory that the procurement and use of medicines in Govt. hospitals and public sector undertakings be done based on the NEML .Such procurement should be through transparent procedures. Regular training and incentives to promote use of medicines in the NEML should be provided.

Irrational and Hazardous Drugs

1. Given the proliferation of irrational and hazardous medicines in the market, a special committee of the DTBA should be set-up to weed out all such medicines including irrational Fixed Dose Combinations (FDC) within a stipulated period. Hence forth medicines and fixed dose combinations which are not mentioned in standard text books and other such authentic sources of pharmacological information should be banned and should not be allowed to be marketed. All existing medicines should be re-evaluated at regular intervals on the basis of expert opinion on their rationality, efficacy and need.
2. Injectable contraceptives, transdermal implants and anti fertility vaccines should not be used in the National Family Planning Programme.
3. Adverse Drug Reaction (ADR) Monitoring Centres should be set up in all states of the country and be provided with sufficient resources.
4. When a substantial number of ADRs are reported either in India or abroad for a drug, the same should be referred to the DTAB for withdrawal.

Generic Drug Use

In order to encourage use of medicines in generic names, all medicines sold under generic names should be exempt of duties and taxes. All packages of medicines should carry the generic name more prominently than the brand name.

Medical Education

The curriculum for medical education should include the concepts of essential drugs and rational prescription practices.

Indian Patents Act

1. The Govt. should keep advocating for keeping TRIPS out of WTO provisions and advocate for reopening the issue of exempting the developing countries from Product Patent.
2. The Govt. should ensure that all the flexibilities in the Act are used to promote health and development of the indigenous drug industry.
3. The Govt. should closely monitor the application of Patentability criteria for granting of Patents to ensure that trivial Patents are not allowed and ever greening of existing Patents does not take place.
4. The Govt. should liberally interpret the Doha Declaration of 2001 by declaring situations of emergency/urgency in the case of diseases that are present in epidemic or endemic forms or where their prevalence constitutes a health emergency. In such situations Compulsory licenses should be issued without delay.
5. Govt. should also facilitate the issue of compulsory licenses to remedy situations of non availability or high price of a patented drug or where an export market exists and is not being addressed.

Drug Production and Availability

1. To ensure production from the basic stage, ratio parameters between manufacture of formulation and bulk drugs should be reintroduced.
2. Production Control mechanisms should be introduced to ensure that all manufacturers produce a certain proportion of drugs from NEML that are Essential.
3. The new policy of allowing 100% equity participation of MNCs in the pharmaceutical sector needs to be changed and majority equity participation by the multinational companies should only be permitted if new technology is brought in by them for manufacturing and research.
4. Restrictions in the form of tariffs and other non-tariff measures should be imposed on the import of bulk drugs or formulation for which adequate production capacities exist in the country.
5. Prevailing systems of loan license or third party license should be abolished. Mention of the name and address of the manufacturer should be clearly indicated on the label of each medicine, and the license holder should be held responsible for all complaints, compensation and replacement of medicines.

Drug Pricing

1. drugs should be brought under price control given the fact drug expenditure in India is more than half the health care expense and also because more than 80% of health care expenditure is met by patients themselves. Mechanisms that are transparent and easy to administer should be put in place to control prices and the system of price control should benefit the efficient producer. In no case should the mark up allowed be more than 100%.
2. Trade margin, those to including wholesalers and retailers should not go beyond 30%.
3. National Medicines Pricing Authority should be established as a quasi judicial body which should be given sufficient legal power to punish manufacturer for violation of ceiling prices.
4. For imported medicines, provision of cost data and manufacturers price certificate should be made mandatory.
5. All cancer and HIV/AIDS medicines and orphan medicines should be exempt from all taxes and duties, including import duties.

Public Sector

The production of drugs for the poor and the neglected diseases can only be ensured by making public sector companies major producers in these areas. Public sector medicine companies such as IDPL and HAL should be revived and they should be provided with the support in the form of sectoral reservation, preferential treatment in the cases of Govt. purchases, etc. These companies would need to be provided a leading role in drug manufacture in the case of compulsory licenses issued in situations of national emergency and extreme urgency. New public sector companies should be promoted for producing those essential medicines that are not being produced by private companies at an affordable cost.

Research and Development

1. A major national effort should be made to increase original drug research based on the strength of our national research institutes, laboratories and the Universities and also on the biodiversity and the medicinal plant wealth of our country. The research institutions should be provided with adequate funds for drug research .Regional drug research centres may be established in states where infrastructural facilities are already available. Universities should be encouraged to offer courses so as to produce adequate and high quality human resource pool for modern drug research related activities. The Public Sector should be promoted to play the leading role in R&D activities.
2. Public funded Research Laboratories should co-ordinate their activities. The research activities of publicly funded research organisations should not duplicate empirical drug discovery projects in the pharma R&D model, but should concentrate on generating the knowledge base for the identification and exploitation of new intervention points for medicines.
3. All medicines developed in the country should be exempt from taxes and duties for 10 years.
4. A comprehensive legislation on the ethical conduct of clinical trials should be enacted in line with the Helsinki Declaration and other international covenants, treaties and declarations so as to provide for strict guidelines for obtaining informed consent, for protection of the health of subjects of such trials.
5. Outsourcing of clinical trials for MNCs should be closely monitored by a specially constituted Standing Ethics Committee set up in each state.
6. All information about protocols and the results of the clinical trials approved by the DGCI should be in the public domain.
7. Phase IV of the clinical trials should be mandatory and should not be replaced by the PMS studies by he pharmaceutical companies.

Quality Control and Drug Information

1. The manufacturer should be fully responsible for the quality of a medicine. A separate Food and Drug Court should be made responsible for redressal of complaints and for trial of those responsible for manufacture and sale of spurious and sub-standard drugs.
2. The Drugs and Cosmetics Act should be suitably amended to provide for exemplary punishment to those found guilty.
3. The drugs control organisation both at state and central levels should be adequately strengthened in terms of infrastructural facilities and human resources.
4. Each state should have at least one well equipped drug testing laboratory under the control of the state drug controller.
5. The state and central drugs controllers should have their own websites. Among other information these websites should publish updated information on banned and withdrawn drugs including their brand names as well the current laws in operation.
6. A consensus should be developed after discussion with manufacturers of all sectors for developing minimum benchmark of good manufacturing practice which then can be embodied in the Schedule ‘M’ of the Drugs & Cosmetics Act.
7. Consumers should be allowed to get tested medicines of doubtful quality at any Govt. approved test laboratory.
8. New colleges of pharmacy should be opened to eventually ensure that all retail pharmaceutical outlets have the services of a trained pharmacist.
9. The outdated Magic Remedies Act should be replaced by a new Act.
10. To disseminate unbiased information of medicines, Govt. should develop an independent process for information. The National Formulary should be updated and published regularly. Standard treatment protocols and guidelines for common ailments and for every tier of the health system should be prepared and disseminated. Doctors, pharmacists and staff nurses should be trained in treatment protocols and guideline. All hospitals and medical centres should be encouraged to prepare and use their own formularies.

Drug Promotion

1. A National Ethics Committee on Promotion of Medicines (NECPM) in which there is adequate representative of civil society organisations should be formed to monitor all promotional efforts
2. A code of ethics for marketing of medicines should be adopted by NECPM and made obligatory for all the manufacturers.
3. All promotional materials for health professionals should be screened and approved by NECPM and all advertisements in the regional press be scrutinized and approved by a state level Ethical Promotion Committee.
4. Gifts except minor items, inducements, sponsoring of meetings and entertainment of the members of the medical profession and those who are related to drug prescription, purchase etc by drug companies should be banned so that these do not influence prescribing practices.
5. Drug companies should contribute funds to the drug control authority for the conduct of Continuing Medical Education programme for doctors
6. A cap on drug promotional expenditure drug companies should be fixed and enforced.

Pharma Market..............

India has a vast Pharma market, and is rightly celebrated in international circles for making medicines very affordable and low priced. As of 2003, the Indian industry was supplying 20 percent of the world’s drugs (by volume) and is currently one of the largest pharma industries in the world (by volume). At least 60 manufacturing plants in India have US Federal Drug Administration (FDA) approval, second only to the United States. Currently a dozen top Indian Companies are major suppliers to the US and European markets as well as China.

In 2005, India’s drug pieces were among the lowest in the world (dollar terms and even in purchasing power parity terms) with China as the possible exception for even lower prices.

India’s homegrown drug companies have outstripped Western MNCs in India (see Table 1 and 2 and3). But in comparison to worldwide pharma majors, the sales of entire Indian drug industry was US $10 Billion (about 40,000 Cr) in 2005 whereas the sales of the top 15 companies in the world in 2004 was more than US $400 Billion. In 2004, US drug companies spent more than US $33 Billion in research whereas Western drug companies spent only US $33 Million in India on R and D. Indian drug companies all put together spent US $0.3 Billion on R and D. Just to give an idea of the disparity, merely world pharmaceutical packaging demand will reach US $22.20 Billion in 2007. The US will remain the largest consumer of drug packaging while China generates the fastest gains.

Nevertheless, the booming Indian pharma market coming to the rescue of generics world over, especially by making low priced antiretrovirals, is a good part of the story. The not so good part is that the Indian pharma scenario, as far as the ordinary poor consumer is concerned, is a failure of the market.

As a result of this extreme failure and failure of regulation in the absence of well-functioning markets, the drug (medicines) availability situation in India is one of poverty amidst adequacy there is inadequate access and supply of even essential drugs to the poor despite adequate drug production. Adding to this misery is the poorly functioning public health system. While the sales of Indian pharma companies are increasing steadily (approximately Rs.40,000 Cr during 2005, including exports), the total government expenditure by both Central and State Governments would be of the order of a mere Rs.3000 Cr, with the Southern States spending 15% on health of the total budget while Assam, Bihar, Up and Orissa would spend only 5 percent! Share of drugs to total treatment costs vary from 50 to80 percent depending on rural/urban locations and inpatient /out patient treatment. All-India figures per capita annual drugs and other medical expenditure (rural) is Rs.294 out of Rs.380 for health as a whole.

Table.1 Earnings by top 25 Indian Pharma Companies

Rs (Crore)	Net Sales		Exports (FOB)		Imports (CIF)		Exports as % of sales
	2004-05	2003-04	2004-05	2003-04	2004-05	2003-04	2004-05	2003-04
Ranbaxy Laboratories	3497.2	3398.27	2335.02	2346.07	716.64	531.03	66.8	69.0
CIPLA	2181.26	1842.24	1053.21	812.28	447.74	284.23	48.3	44.1
Dr. Reddy’s Laboratories	1557.69	1666.63	913.90	981.55	228.29	218.67	58.7	58.9
Aurubindo Pharma	1085.02	1259.89	554.62	642.04	530.69	539.58	51.1	51.0
Lupin	1161.13	1119.28	553.27	568.78	272.94	274.66	47.6	50.8
Orchid Chemicals & Pharma	638.40	680.81	520.04	531.54	283.94	258.56	81.5	78.1
Ipca Laboratories	671.17	602.53	390.97	340.16	86.52	84.99	58.3	56.5
Biocon	646.51	502.51	376.15	299.98	281.63	211.17	58.2	59.7
Matrix Laboratories	636.76	529.48	336.60	297.59	160.05	98.37	52.9	56.2
Wockhardt	846.74	729.48	308.10	280.47	107.75	87.79	36.4	38.4
Divi’s Laboratories	347.38	302.83	301.59	258.72	67.93	57.85	86.8	85.4
	995.62	839.36	275.10	204.11	108.01	91.67	27.6	24.3
Strides Arcolab	305.31	274.39	266.64	248.28	68.18	54.73	87.3	90.5
Panacea Biotec	325.54	261.62	227.74	161.55	148.06	112.84	70.0	61.7
J B Chemicals & Pharma	35775	303.54	197.85	154.85	16.72	20.93	55.3	51.0
Cadila Healthcare	1063.40	1034.90	138.00	177.30	128.50	107.20	13.0	17.1
Glenmark Pharmaceuticals	463.20	320.02	130.13	48.95	43.70	29.67	28.1	15.3
Nicholas Piramal India	1232.25	1269.05	126.32	97.15	150.79	128.39	10.3	7.7
Alembic	524.46	56.46	105.91	124.29	80.68	71.09	20.2	22.3
Dishman Pharmaceuticals	157.22	123.25	105.88	83.42	40.63	26.05	67.3	67.7
Natco Pharma	154.40	129.61	91.85	61.67	11.12	9.64	59.5	47.6
Torrent Pharma	497.59	443.08	80.88	44.94	120.54	93.70	16.3	10.1
FDC	321.50	279.07	80.08	44.11	14.57	17.56	24.9	15.8
Unichem Laboratories	390.64	353.45	59.12	41.13	8.84	6.41	15.1	11.6
Medicamen Biotech	48.11	48.78	37.80	34.44	7.53	2.98	78.6	70.6
Total of 25 companies	20106.67	18870.53	9566.77	8885.37	4131.99	3419.76	47.6	47.1

Table 2: Highlights for Top 50 Indian Pharma Companies

	(Rs Crore)
	FY ‘ 05	FY ‘ 04	% Change
Net Sales	29402.88	27380.32	7.4
Other Income	1078.40	1047.28	3.0
Raw materials cost	14009.80	13190.92	6.2
Staff cost	2612.64	2216.37	17.9
Other expenditure	8069.18	7055.27	14.4
PBDIT Interest	6438.54	6309.47	2.0
Depreciation	478.29	594.44	-19.5
Profit before tax	1005.66	880.94	14.2
Taxation	4963.53	4836.38	2.6
Net profit after Tax & exceptional items	1028.48	804.68	27.8
Equity capital	4068.17	3878.22	4.9
Note: Totals may not add due to rounding off	1593.18	1434.62	11.1

Table 3: World’s Top15 Pharma Companies Register 28% Growth in Net Profit, 10.6% Rise in Sales in 2004

(US $ Million)	Sales		Cost of Mfg, Selling, R&D		EBDIT		Net earnings
Company Name 2004	2004	2003	2004	2003	2004	2003	2004	2003
Abbott Laboratories	19680	17280	15782	14306	3898	2974	3236	2753
Amgen	9977	7868	6273	4836	4277	3520	3148	2539
AstraZeneca PLC	21426	18849	16971	14938	4455	3911	3813	3036
Bayer	40602	35872	39232	38731	1370	-2247	823	-1709
Bristol-Myers Squibb	19380	18653	14979	13720	4401	4933	2388	3106
Eli Lilly & Co	13858	12583	10591	9080	3267	3503	1810	2561
GlaxoSmithKline	39224	38133	27376	26557	11849	11576	8288	7964
Johnson & Johnson	47348	41862	34503	31909	12845	9953	8509	7197
Merck & Co	22939	22486	16316	14112	6623	8374	5813	6831
Novartis	28247	28864	21708	18975	6539	5889	5767	5016
Pfizer	52516	44736	38509	41490	14007	3246	11361	3910
Roche	27641	25143	22765	21170	4876	3973	5870	2472
Sanofi-Aventis	34680	30509	23543	21400	11138	9109	7159	5589
Schering-Plough	8272	8334	8488	7776	– 216	558	-981	-92
Wyeth	17358	15851	13208	12152	4150	3699	1234	2051
Total for 15 companies	403148	363023	310244	291152	93479	72971	68238	53224
Exchange Rate – As on 31/12/04; $ 1 Euro = 1.365 1Chf =0.885 As on 31/12/ 03; $ 1 Euro = 1.265 1Chf =0.815

More players in an uncontrolled market have meant only a wide range of prices for the same drugs. On the other hand, you have the same drug being sold by different companies (and sometimes by same company) at vastly different prices. There is not even a direct relation between top-selling drugs and real need as per the disease and illness conditions prevalent. These severe distortions are compounded by poor regulation, nexus between medical profession and Pharma companies and their aggressive and often unethical marketing.

2. Marketing of Top 300 Drugs in India: A brief Analysis

We now present an analysis of the top-selling 300 drugs of India accounting for Rs.19000 crores sales in India. This analysis of the Indian market is based on the October 2003 data of ORG- Nielsen. This data is collected from a sample of around 280 outlets in India and is based on data from wholesale dealer’s sales to retailers. It is not based on retail sales. It is indicative, of market trends in general. And in view of the sample taken and the exclusion of Institutional sales, it is likely to be an underestimate of the total volume of sales.

This analysis of the top-selling brands, along with the analysis of the variation in drug prices already discussed gives some insights into the nature of the Indian drug market.

The sales from 300 brands alone are huge and put the government estimates of the sales of the pharmaceutical sector into question. The government quotes lower figures. The total Moving Annual Total of from the retail sales of 300 brands alone (there are more than 20,000 formulations in the market) is a whopping Rs.18,000 Crores. This figure of Rs.18,000 Crores would only be a part of the total sales. The final figure of the total sales does not take into account institutional and governmental purchases, which would also be of very considerable magnitude. Some industry estimates put the figure to Rs.40,000 crores (for instance see (www.pharmabiz.com) editorial, June 20, 2001; “A Rs.40,000 crores industry”0. This has to be seen in the context of sales of top-selling drugs in the world (Table 4). But it is interesting to note top 300 brands sell 50 percent of drugs by sales value (of Rs.18,000 Cr) in India.

Global pharmaceutical sales tallied in at $500 Billion. Of that revenue, $230 Billion was in North America. That’s more than double the dollar sales booked in the European Union. But cost differences become even more striking when one looks at the nine top-selling medicines in the world. Comparing the global sales figures last month reveals that all but one of these medicines won most of its dollar sales in the United States. The reason is not likely merely that people in the US use more medicine, but also that they are more expensive.

Table 4: World’s Top-selling Drugs, 2003

Drug	Purpose	Maker	Global Sales ($bil)	US Sales ($ bil)	% of sales in US
Lipitor	Lowers cholesterol	Pfizer	$10.3	$6.8	66%
Zocor	Lowers cholesterol	Merck	6.1	4.4	72
Zyprexa	Anti –psychotic	Eli Lilly	4.8	3.2	66
Norvasc	Lowers Blood pressure	Pfizer	4.5	2.2	40
Erypo (Procrit)	Treats Anemia	Johnson & Johnson	4.0	3.3	83
Ogastro/ prevacid	Treats Ulcers	Takeda & Abbott Laboratories	4.0	4.0	100
Nexium	Treats Ulcers	Astra Zeneca	3.8	3.1	82
Plavix	Blood thinner	Bristol-Myers Squibb	3.7	2.2	59
Seretide (Advair)	Treats asthama	GlaxoSmithKline	3.7	2.3	62
Zoloft	Anti-depressant	Pfizer	3.4	2.9	85

2.1 Top 300 Brands and their Relation to the National Essential Medicines List.

There are a total of 354 drugs in the National Essential Medicines List, which are adequate to take care of the majority of the health needs of the population during outpatient or in-patient care. If we examine the list of top 300 brands (as per ORG-Neilson Oct 2003, see Table 5 for a partial list), we find that only 115 brands are of drugs that are mentioned in the National Essential Medicines List (NEMI) 2003, i.e. only 38% of brands of the top selling ones are of drugs mentioned in the NEML. The other 62% are of drugs which do not find mention in the NEML. Of course 62% brands comprise drugs that are higher priced alternatives without a clear therapeutic advantage, and many drugs that are unnecessary, irrational and even hazardous. The number represented by these 115 brands is only 68.

That means the majority of the top selling brands are drugs which are outside the National Essential Medicines List, which means that the majority of the drugs which are the most cost-effective for the treatment of property health needs of the people are not the ones which are selling the most. (See also Table 6.)

A dramatic illustration of the lack of public health relevance of these top-selling preparations is the case of preparation for iron deficiency anemia, which is one of the India’s most prevalent public health problems. (See Table 7).

There is not a single preparation in the top 300, which has the ingredients for an anemia preparation as mentioned in the National Essential Medicines List.

The top selling preparation (Dexorange) is patently irrational (See chapter 3) while others contain substances which are not required (e.g in Fefol-Z), and which can in fact impair iron absorption. (See also Table 7.)

Table 5: Top – Selling 25 Brands in India as per ORG-Neilsen Retail Audit, Oct 2003)

Sl No.	Brand Name	Uses and Remarks	Moving Annual Total in Rupees Crores
1	Corex	Cough suppressant. Abused as drug of addiction because of presence of codeine.	88.18
2	Becosules	Multivitamin unnecessary preparation	79.74
3	Taxim	Bacterial infections	77.05
4	Voveran	Pain relief	76.14
5	Althhrocin	Bacterial infections	68.46
6	Human Mixtard	Diabetes Mellitus	63.39
7	Cifran	Bacterial infections including Typoid	62.70
8	Liv-52	Ayurvedic Liver preparation	62.67
9	Asthalin	Asthma	61.76
10	Sporadex	Bacterial infections	61.71
11	Betnesol	Allergy	61.11
12	Zinetac	Dyspepsia, Ulcer disease	60.70
13	Neurobion	Irrational Multi vitamin preparation	60.27
14	Nise	Hazardous drug for pain relief	58.31
15	Digene	Antacid	57.86
16	Dexorange	Irrational preparation for anemia	57.65
17	Phexin	Antibiotic for Bacterial infection	57.03
18	Mox	Bacterial infection	56.36
19	Cardace	Hypertension, Heart failure, much cheaper alternatives exist.	55.31
20	Rabipur	Vaccines against Rabies	54.40
21	Omez	Peptic Ulcer	53.52
22	Ciplox	Bacterial infections	51.69
23	Combiflam	Analgesic combination	49.02
24	Aten	Hypertension	48.87
25	Augmentin	Costly antibiotic	48.63
		Total	1532.53

The mere inclusion of a drug in the National Essential Medicines List does not translate into affordability for the patient, because most of the drugs included in the NEML, are outside price control. Even when the drug is under National Essential Medicines List because of the lack of regulation over drug prices, it is often the costlier version that sells more: For example, Ciprofloxin is sold by Ranbaxy at Rs.8.96 a tablet. Yet the cheapest brand of Ciprofloxin at RS.2.90 does not sell as much.

Table 6: Top Selling 10 Categories of Drugs in the Top 300 Brands: Where is the people’s Money going.

Type of drug Category	No. of Brands	Moving Annual total (in crores of rupees)	Remarks
1. Anti-infectives	65	1650.02	Most frequently used & abused drugs when antibiotics are given for fever sue to viral infections.
2. Analgesics	26	705.06	Hazardous analgesics like nimesulide are one of the top sellers.
3. Endocrine disorders like Diabetes mellitus, hormones	25	694.10
4. Multivitamins and minerals	27	651.29	Contains predominantly non-essential drugs in all kinds of irrational combinations.
5. Drugs for cardiovascular disease	26	601.64	The top selling cardiovascular drug is one that has little therapeutic advantage over less costly alternatives.
6. Drugs for respiratory system, including cough preparations	21	512.59	Cough syrups sell more than drugs for asthma.
7. Drugs for gastrointestinal system	20	427.21	Their large sale is also the result of over prescription.
8. Drugs for allergy	10	326.51
9. Anticonvulsants	9	221.35
10. Hematinics	6	128.13	Contains such irrational wonders of the pharmaceutical world as Dexorange (57 Crores) which till recently contained animal blood from slaughter houses, Hepatoglobine, etc.

2.2 Top-Selling Drugs outside the NEML.

These are diverse types and include:

• Higher priced brand of either the same drug or a higher priced alternative to a lower cost essential drug.
• Irrational drugs and irrational combinations of antibiotics, vitamins, analgesics which include unsafe and hazardous drugs.

Examples abound in this regards:

• Cifran brand of Ciprofloxin is the largest selling antibiotic, whereas it is the costliest among the ciprofloxins. Other brands of ciprofloxin, e.g. Zoxan which are 3 times sells 5 times.
• Ramipril is an angiotensin converting enzyme inhibitor like enalapril. It has no therapeutic advantage over enalapril, and is costlier. enalapril is mentioned in both the National and WHO list of medicines as being representative of the class of ACE inhibitors, while ramipril has not been.; Yet sells more than enalapril.
• Penicillins including amoxicillin, ampicillins are effective antibiotics for a variety of infections Oral.
• Cephalosporins are to be used in certain situations only and mainly when it is not possible to administer oral penicillins because of penicillins allergy. Yet according to the sales figures brands of Cephalosporins (Phexin, sporidex) clearly outperform penicillins, which indicate inappropriate use. The indications for erythromycin are similarly limited. However the sales figure for erythromycin is also higher than of penicillins.
• This is another area of concern in the Indian drug industry. Irrational combinations of drugs, which only add cost but no therapeutic value, are touted as effective remedies and promoted aggressively.

Table 7: Most common and important Public Health Problem of India According to the Pharmaceutical Industry: Not Anemia, but B-Complex Deficiency!

Brand	Rank in Top 300 Brands	Moving Annual Total (Rupees Crores)
Becosules	2	79.74
Revital	27	47.64
Polybion	42	40.85
Zincovit	60	32.26
Cobadex forte	88	26.10
Methycobal	116	21.87
Zincovit	118	21.65
Neogadine	119	21.52
Riconia	125	20.78
R.B. tone	129	20.21
A to Z	145	19.07
M2tone	157	18.22
Supradyn	221	1525
Becadexamin	229	14.63
Raricap	239	13.89
Becosules-Z	295	12.03
Optineuron	297	11.97
		437.68

2.3 Irrational drugs of No Therapeutic Value in the Top 300

Consider the following:

• Irrational drugs like Electral (since rationalised), or drugs which are used irrationally like Evion, Glucon-D, Deca-durabolin are top selling drugs, Protein products are irrationally prescribed and irrationally priced.
• Irrational combinations of vitamins , minerals and other ingredients including ginseng (which has supposedly aphrodisiac properties), or even and outmoded and dangerous ingredient like animal hemoglobin from slaughterhouse blood, fresh liver extract, are passed off as tonics, haematinics, and food suppliants to a gullible population via the medium of obliging Doctors. Most of these preparations would hard to find in any pharmacoepia in the world, but the drug regulatory authorities do not find anything wrong in approving their manufacture, Examples include Revital elixir Neogadine, hepatoglobins, etc.
• Irrational combinations of antibiotics: the most common being ampicillin plus cloxacillin which is widely used inappropriately.

2.4 Unsafe and Hazardous Drugs Among the Top 300

• Preparations containing animal tissue without therapeutic rationale. e.g, Hepatoglobin containing fresh liver extract carry the risk of transmitting infection.
• The high sales figures for codeine containing cough syrups are a matter for concern. Both Corex (the Number 1 brand in the country with sales of Rs.88 Crores) and Phensedyl (rank 29, sales Rs.47.30 crores). These syrups are widely used especially in the northeast as drugs of addiction because of the presence of codeine. They are also smuggled into neighbouring countries like Bangladesh and Myanmar. Does the abuse of these syrups contribute to their high their high turns over? In contrast Glycodin contains detromethorphan that is a safe constituent. It however does not sell as much (rank 259, sales Rs.13.15 crores).
• Nimesulide, which is one of the best-selling analgesic drugs in India, is not approved in most of the developed world because its side effects on the liver.

2.5 Preponderance of Combinations Among the Top 300.

• A significant number of the top selling formulations are combinations of drugs, rather than single ingredients. In fact there are 118 combinations in the list of 300. The Majority of the combinations are irrational. Only around 20 of these combinations are rational, the rest are combinations, which lack any therapeutic rationale for being combined.
• The pattern of production and the pattern of sales do not adequately reflect the real health needs of the people. There is overrepresentation of costly antibiotics, irrational multivitamin preparations, cough syrups, ineffective haematinics, pain balms, rather than cost-effective drugs of real therapeutic value.
• The sales figures reflect the fact that in India, drugs which are not considered essential sell more than rational and essential drugs, that costlier drugs most often sell more than cheaper alternatives (even those made by well known manufacturers), and downright irrational and hazardous drugs are among the Top-selling sellers. The majority of sales are coming from the sales of drugs not considered relevant by experts for inclusion into an essential medicines list, and not considered important by the government for regulation of their price.

Banning of Liver Extract

A large number of pharmaceutical products with poor rationality profiles are being manufactured and marketed by drug companies in India today. Most of them are fixed dose combinations of drugs and vitamin preparations. No control on their has been achieved despite frequent regulatory interventions. One such controversial preparation is the brands containing crude animal liver extracts with a few other ingredients for the treatment of megaloblastic anemia. These formulations have been found to be carrying infective diseases from animals to humans besides causing allergic reactions as they are containing biological products. Currently there are six leading brands of liver extracts formulations available in the market for the treatment of anemia. These are Livogen, Ibberol, Plastuules B12, RB Tone, Heptaglobine and Hep-Forte. Recent medical studies conducted in India and abroad have questioned the relevance of the continuing use of anti-anemic preparations containing multiple ingredients like Liver, iron, folic acid, vitamin B12, copper, manganese, etc. Some of these ingredients are unnecessary, wasteful and only increase the cost of therapy and risk of infection, the studies have pointed out. But none of the pharma companies had taken any steps to withdraw the liver extract from their products or reformulate them although the use of liver extract has been banned in several countries ago.

The need to ban the use of liver extracts in drug preparation was first raised by Pharmabiz.com in April 2001. The issue was subsequently taken up by Ahmedabad based Consumer Education Research Centre with DCGI. But no serious action was initiated by the drug Controller General of India in this regard. DCGI is reported to be now moving to prohibit the use of liver extracts. A circular is expected to be issued in this regard asking the pharma companies to replace liver extract with pure Vitamin B12. Merck, the leading player in this segment, meanwhile, has decided to withdraw liver extract from its brand, Livogen. Liver extract has been the key ingredient of Livogen tablet and the tonic marketed by the company. The decision of the company is in the wake of its acceptance of the fact that this ingredient has no place in the modern therapy as it is unsafe and irrational. Liver extracts used to be the only option before the development of folic acid and vitamin B12 in pure form. But the drug companies have been avoiding use of vitamin B12 in place of liver extracts despite its abundant availability. Reluctance of the drug companies is mainly on account of the cost of factor. Regulatory authorities should only know that resistance of pharma companies to recall an established product or change the composition of a well known brand do cause a lot of damage to the public. In matters like this, a faster regulatory initiate is called for.

This brief analysis of the Top-selling 300 brands suggests that the Indian doctors are prescribing drugs without adequate concern for evidence of their efficacy, safety, and cost. This is because of the poor access to unbiased information on drugs, for doctors as well as lay persons in India, compounded by the aggressive and misleading drug promotion by the drug industry. The result is increased health care costs for the patients, irrational use of drugs, and exposure of patients to the risks of unsafe drugs.