Petition against irrational FDCs

[Guest guest]

Kind attention NetRUMians,

Below is personal mail from Dr Gopal Dabade copied as fair use for

all NetRUMians. All big personalities of RUM are involved in this

petition which appears at the end of message. Please contribute your

might to them who are relentlessly crusading against irrational FDCs

in India.

Thanks

Dr Vijay Thawani

Group Owner

NetRUM

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Dear Dr Vijay Thawani,

Greetings from Drug Action Forum - Karnataka, Dharwad,

I am pleased at your response for my posting on the e-forum

regarding Fixed Dose Combinations (FDC).

This letter is further continuation of that. To give you a back

ground. Few organisations have come forward to file a petition in

the Chennai High Court regarding the case on FDC. A copy of the

petition is attached for your reference.

Sir. as a qualified and experienced person in this field of

medicine, I seek your support and help. Do let me know as to how you

would like to be a part of this case and help it. Your help in any

way will be appreciated though I have few suggestions.

You can be a part of this petition by filing a similar case and

supporting it. For this you will need to get in touch with a lawyer

in Chennai and ask him or her to file a petition and represent on

your behalf. Your presence will not be needed for every hearing but

it would be good if you can attend few hearings to get a sense of

what is happening. Or may be if you have Pharmacology friends in

Chennai - they can also be part of the petition.

You can disseminate this petition among like minded Pharmacologists

and get feed back and or support from them. Even if few

Pharmacologists association pass a resolution endorsing the contents

of this petition it would be good support.

You can write articles in professional magazines or e-forums about

this issue and highlighting the petition and seek support.

Any other way you think you can help.

These are just some stray ideas that occur to my mind that I have

mentioned but may be there are other better ways that you may think

and you can support.

If you need any more information please do contact me or you could

contact my friend Mr Srinivasan S (mobile number 09998771064) at

Baroda - to whom I am marking a copy of this letter.

I do look forward to hearing from you.

Best wishes

Gopal

--

http://novartisboycott.org/petition

Dr Gopal Dabade,

57, Tejaswinagar,

Dharwad 580 002

Tel 0836-2461722

Cell (0)9448862270

www.jagruti.org

www.aidanindia.org

www.daf-k.cjb.net

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IN THE HIGH COURT OF JUDICATURE AT MADRAS

[sPECIAL ORIGINAL JURISDICTION]

M.P. No. _____ OF 2008

IN

W. P. NO 35844 OF 2007

1. All-India Drug Action Network (AIDAN),

Through it¡¦s Co - Convener Dr. Mira Shiva

A-60, Hauz Khas,

New Delhi - 110016.

2. Dr Anant R Phadke, MBBS

Medico Friend Circle,

Registered Non Profit Public Trust having its office

11, Archana Apartments Kanchanjunga Arcade,

163, Solapur Road,

Hadapsar,

Pune ¡V 411028.

Maharashtra

And also at:

Block-8, Ameya-Ashish Co-op. Hsg. Society,

Near Kokan Express Hotel,

Off Karve Rd.

Kothrud, Pune ¡V 4110038,

Maharashtra.

3. Low Cost Standard Therapeutics (LOCOST),

Registered Public Trust having its office

Through it¡¦s Managing Trustee, Shri S. Srinivasan

1st floor, Premanand Sahitya Bhavan,

Dandia Bazaar,

Baroda ¡V 390001.

4. Drug Action Forum-Karnataka

Through it¡¦s Managing Trustee Dr Gopal Dabade

57, Tejaswinagar,

Dharwad - 580 002

Karnataka

5. CONCERT,

(Centre for Consumer Education, Research, Teaching, Training and

Testing),

Through it¡¦s Managing Trustee, Mr. R. Desikan at

4/386, Ram Garden,

Palavakkam,

Chennai - 600 041. ¡KPetitioner/Proposed

Respondents

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Versus

1. Confederation of Indian Pharmaceutical Industry (SSI)

Rep. by its Chairman Mr.T.S.Jaishankar

Quest Life Sciences (P) Ltd.,

SDF III, MEPZ, Tambaram,

Chennai 600 045.

Respondent/Petitioner

2. The Drugs Controller General (India)

Ministry of Health and Family Welfare,

Government of India,

Nirman Bhavan, New Delhi 110 011. ¡K

Respondent/Respondent

AFFIDAVIT OF R. DESIKAN

I, R. Desikan, S/o. Raghavachariar, Hindu, aged about 75

years, residing at No.2/228, Chinnandikuppam Road, Vettivankeni,

Chennai 600 041, do hereby Solemnly affirmed and sincerely state as

follows:

1. I am the 5th Petitioner in the above mentioned Petition to

implead and I am well acquainted with the facts and circumstances of

the case.

2. I am filing the present affidavit on my behalf and on behalf

of the other 4 Petitioners.

3. The present Petition to implead is filed by All-India Drug

Action Network (AIDAN) Medico Friend Circle Low Cost Standard

Therapeutics Drug Action Forum-Karnataka CONCERT, (Centre for

Consumer Education, Research,

- 3 -

Teaching, Training and Testing) partly in support of the letter

dated 14.08.2007 issued by the 2nd Respondent and in public

interest. The said letter has been

issued in the interest of public and we the Petitioners herein are

concerned about the irrational and improper licensing procedures of

several fixed dose combination (FDC) Drugs that are prevailing in

the market.

4. The Petitioner No.1, the All India Drug Action Network

(AIDAN) is an internationally well-regarded and reputed all-India

network of socially concerned consumer and health action groups,

medical and health professionals and academics from medical

colleges. AIDAN has been active since 1982 in advocating a rational

drug policy based on essential generic drugs, weeding out of

harmful, irrational, wasteful and useless drugs in the market. It

has brought out several publications and critiques of drug policy

pronouncements of India, promoted awareness among the public and

media. All the five Petitioners are part of the AIDAN as well as

Medico Friend Circle and another all-India network called Jan

Swasthya Abhiyan, a national and international movement advocating

access to health care as a human right.

5. Dr Mira Shiva, M.D (Internal Medicine), currently co-

convener of All-India Drug Action Network (AIDAN), and Director for

Initiatives in Health and Equity, and formerly Director of Women,

Health and Development and Rational Drug Policy (formerly Public

Policy Division) of the Voluntary Health Association of India

(VHAI), has been active over 30 years in the advocacy of a pro-

people drug and health policy. She is the first recipient of the

Dr. Olle Hansson Award for showing moral courage and her

contribution to rational use nationally and globally. She was part

of the Government of India Committees on Price Control Review and

Pharmaceutical Research and Development as well as the National

Working Group on Patent Laws, Health Action International, Action

for Rational Drugs Asia (ARDA), and Women and Health (WAH!)

network. She was the National Focal Point for the National Profile

on Women, Health and Development ¡V a WHO initiative with VHAI, later

published as a report she helped co edit. She has edited Rational

Selection of Drugs (1986), Rational Drug

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Policy (1986), Investigation of IV Fluid Contamination ¡V a report,

Banned and Bannable Drugs (1996), She is one of the founder members

of People¡¦s Health Movement. Dr Mira Shiva is also the Chairperson

HAI- AP, Chairperson Task Force on Consumer Education; Task Force on

Safety of Food & Medicine (MOHFW); Member Expert Committee on

Safety of Medicines & Medical Devices (National Human Rights

Commission), Coordinator Initiative for Health, Equity & Society; co-

editor Towards Comprehensive Women's Health Policy & Programme

published by SAHAJ Baroda/WAH! Pune, 2002.

6. Petitioner No.2, Medico Friends Circle (MFC), registered as

a public trust at Pune. MFC is an all-India network active since

1975 of socially concerned health action individuals, medical and

health professionals and health researchers and academics from all

over India. MFC members have been active in the Drugs issue,

campaign against hazardous contraceptives, the Bhopal Gas Tragedy

and follow-up in terms of epidemiological research, reaching relief

to the affected and legal follow-up, some of which in the Hon¡¦ble

Supreme Court.

7. Dr Anant Phadke, MBBS, is a well-regarded senior member of

the Medico Friend Circle, and currently Co-ordinator of SATHI-CEHAT,

the action center of Anusandhan Trust, evolved from CEHAT. SATHI-

CEHAT has been a leading element in the Jan Swasthya Abhiyan,

largest the nationwide network of health activists in India. Dr

Phadke has been an active player in the the Health and Science

Movement in India for the last 30 years and more. He is well-known

for his contributions through. Medico-Friend Circle, All India Drug

Action Network (AIDAN), Lok Vignyan Sanghatana, LOCOST, etc. He has

been involved in training of Village Health Workers and Primary

Health Care issues since 1978. Dr Phadke has co-authored training

manuals for Community Health Workers and has contributed about 75

and 150 articles respectively in English and Marathi, to various

health magazines and lay-press on different topics related to the

People¡¦s Science and Health movement, especially on the Drug Policy

in India. Dr Phadke has also authored/co-authored books and papers

on pharmaceutical and health policy issues including the classic

study on drug availability in Satara District,

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¡§Drug Supply and Use: Towards a Rational Policy in India¡¨, Sage, New

Delhi, 1998.

8. Petitioner No.3, Low Cost Standard Therapeutics (LOCOST), is

a nationally reputed public trust and NGO based at Baroda, Gujarat.

LOCOST has since 1983 been consistently and ethically promoting the

idea of rational essential drugs by actually manufacturing and

supplying them to those working with the poor all over India on a

not for profit basis. LOCOST has been active in drug policy and

pricing issues and has been an important and authentic source of the

actual costs of making good quality essential drugs stressing on

demystifying technology for the cause of the poor. LOCOST¡¦s

publications in English and Gujarati include A Lay Person¡¦s Guide to

Medicine (2006).

9. S. Srinivasan, Managing Trustee of LOCOST has been active in

the field of health care, low cost drugs, transfer of pharmaceutical

technology to LDCs, issues of disadvantaged children and human

rights, and relief in disaster situations. . He is an active member

of the PUCL, Baroda, SAHAJ (Society for Health Alternatives), Medico

Friends Circle and AIDAN. Srinivasan has also been active in health

care management issues and was the coordinator of Health Care

Administration Education at VHAI, New Delhi as well as has been the

editor of the periodical ¡§Health for the Millions¡¨ (VHAI). He has

authored, coauthored/or and edited Management Process in Health Care

(1982), The Banyan Tree ¡VA Guide to Holistic Health Practitioners,

Vol 1-3 (1989-91), A Guide to Stress Management (1999) and A Lay

Person¡¦s Guide to Medicine (2000) as well as several articles on

drug policy, pricing and related issues in the Economic and

Political Weekly. Srinivasan is a graduate and postgraduate of IIT

Kharagpur and IIM Bangalore.

10. Petitioner No.4, Drug Action Forum ¡V Karnataka is a

registered, independent NGO campaigning for rational drugs and

rational policy. Its members are drawn from diverse back ground

including doctors, lawyers, trade union workers etc. the main

objective of Drug Action Forum ¡V Karnataka is to empower the

consumer with emphasis on policies of the government with regard to

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medicines and health and to promote the Essential Medicine concept.

Some of its publications include ¡§Hepatitis ¡V B vaccination:

Misleading Policy and Promotion¡¨.

11. Dr Gopal Dabade is a qualified ENT surgeon and has been

involved in the consumer awareness programmes for over two decades.

He also worked, for a period of three and half years with Civil

Society in European Parliament on the issue of Patents and Access to

Medicine as part of a German NGO ¡§BUKO Pharma ¡V Kampagne¡¨. He is one

of the coauthor for ¡§A Study on Drugs for Treating Anaemia¡¨.

12. Petitioner No.5, CONCERT was registered as a trust in the

year 1997, in Chennai, India. The main objective of the trust was to

establish an Asian Centre in Southern India for Consumer Education,

Consumer Products Research and Testing of International Quality.

This Centre will also provide education and training in all consumer

related subjects and activities catering to the needs of the entire

Asian community.

13. Mr R. Desikan has rendered yeoman service on consumer

related issues over 30 years and is one of the leading consumer

activists of the country.

14. The filing of the present Petition is for the reason that

the Drug Controller of India (DCGI) has directed all States Drug

Controllers to take necessary action with respect to FDCs¡¦,

mentioned in the list that are permitted by the State Drug

Controllers, on the ground that the FDCs licensed by State

Authorities are not permitted by the Office of the 2nd Respondent.

The action to be initiated on several fixed dose combination (FDC)

drugs (more than 300 in number) stating that they are irrational

and/or for not following proper licensing procedures or for lack of

adequate supportive data.

15. The Petitioners state with regard to the definition,

Combination products also known as Fixed Dose Combinations (FDC¡¦s)

are combination of two or more

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active drugs present in a dosage form. FDC¡¦s infact have certain

advantages in certain situations.

16. The Petitioners herein appreciate this move by the DCGI¡¦s

order inter alia for the following reasons:

1. FDCs specified by the DCGI for weeding out (Annexure 1) are

unscientific. The safety of these FDC¡¦s (as also FDC¡¦s in general)

is not studied. FDC¡¦s in general increase the chances of adverse

drug reactions and drug-drug interactions.

2. There are only a handful of FDC¡¦s which are recommended by

standard medical authorities like reputed pharmaceutical textbooks

or the World Health Organisation (WHO). In the WHO¡¦s 14th list of

312 Essential Medicines, only 18 are FDC¡¦s. In the latest list of

March 2007, there are 347 essential drugs that include only 26 FDCs

(for a list see further below). All FDC¡¦s in the market which are

not recommended by standard medical authorities are irrational and

need to be weeded out for a number are reasons:

a) FDC¡¦s are an economic waste when only a single ingredient

drug can do. Unaware patients tend to get exploited as FDCs are

marketed as superior to single ingredient drugs.

Pharmacopeias in general specify only quality test

procedures and standards for single ingredient drugs. Quality

procedures for the FDCs are dependent on the manufacturer¡¦s word in

the absence of scientific third-party validation. In addition, this

overloads the already stretched and strained quality labs as well as

the limited number of drug inspectors (about 1000) in this country.

- 8 -

c) Such a large presence of FDC¡¦s, in different dosages, and

brand names, creates confusion for the prescriber and increases

chances of medication errors that are harmful, and sometimes even

fatal, for the patient.

d) FDC¡¦s apart from confusing patients and scientifically

inclined doctors, pose a problem in price regulation. It is easier

to fix ceiling prices for single ingredient drugs and the NPPA

(National Pharmaceutical Pricing Authority) has limited resources to

deal with the issue of appropriate pricing of FDC¡¦s.

17. The applicant¡¦s appreciates the move by the DCGI for the

above reasons and totally support any move to ensure the

implementation of the DCGI¡¦s order, which has been unfortunately

challenged by Drug Industry representatives.

18. However the Petitioners contend that the order barely

touches the essence of the problem of irrational FDC¡¦s in India and

tends to give the impression of being arbitrary, superficial, and at

best, a tokenistic exercise for the following reasons:

a) The DCGI has not enumerated comprehensive, fundamental

principles of describing drugs and their fixed dose combinations as

irrational.

India¡¦s market is full of irrational fixed dose combinations

(FDC¡¦s). The Applicant states that, recognizing the magnitude of

problem of irrational/unscientific FDC¡¦s in India, the present

action merely touches a small part of the problem even as it gives,

wrongly, the impression of clearing the therapeutic chaos in the

Indian market.

c) The Indian market is also full of inessential and hazardous

drugs which should not have been approved in the first place at all.

These need to be removed within a specified time limit by the DCGI.

d) An analysis of the top-selling 300 drugs as per ORG-

Marg/Nielsen retail audit shows that more than 60 % of them are

irrational.

The order by the DCGI does not touch these FDC¡¦s, which account for

more than 90 percent of the total retail sales of drugs in India.

- 9 -

e) The DCGI also says the list of drugs specified by him do not

have proper approval saying the approvals given by the State

Licensing Authorities (SLAs) are illegal. So most likely these will

be approved if they follow a new procedure specified by him. As a

result the irrational drugs will find their way in the Indian market

again. Unfortunately the State Licensing Authorities (SLA¡¦s) have

been lax and have not followed the DCGI¡¦s guidelines in the matter.

f) The words ¡§illegal¡¨, ¡§irrational¡¨ and ¡§FDCs¡¨ are used

interchangeably by the DCGI (as reported in the press). The

Petitioners submit while most FDC¡¦s are irrational (that is they are

unscientific and do not have any mention in standard textbooks nor

sanction of experts), they are deemed illegal in the instant case

because of improper procedures (including lack of stability studies)

followed in licensing according to the DCGI. Many more otherwise

legally licensed FDC drugs that are currently being sold in the

Indian market, would not pass the rationality criteria anyway. So

why are they not attracting the attention of the DCGI?

g) A single ingredient drug can be also irrational if it does

not meet scientific criteria of rationality of safety and efficacy.

Any COMBINATION OF AN IRRATIONAL DRUG IS ALSO IRRATIONAL. Also

combination of rational drugs is not in general warranted except for

some 26 FDCs mentioned above.

h) A comprehensive move to weed out irrational single

ingredient/fixed dose combination drugs, not merely ¡§illegally¡¨

or ¡§improperly licensed¡¨ drugs, will consider inter alia the

following sources of irrationality:

i) Unscientific drug with no proven efficacy (or at best

doubtful) efficacy in any controlled trial: e.g. Serratiopeptidase,

iron polymaltose complexes (IPC), etc.

ii) Unscientific combinations which may increase adverse

effects: e.g., Ibuprofen + Paracetamol; Paracetamol + diclofenac;

epam + Magaldrate + Oxyphenonium.

- 10 -

iii) Hazardous drug (side-effects of which far outweigh the

benefits), e.g., Nimesulide, Analgin; and/or drugs/drug

combinations, which have shown, increased mortality. e.g. Liv 52 in

alcoholic cirrhosis, antioxidants (See for instance: S. Verma, P.

Thuluvath. Complementary and Alternative Medicine in Hepatology:

Review of the Evidence of Efficacy. Clinical Gastroenterology and

Hepatology, Volume 5, Issue 4, Pages 408-416.)

iv) Combinations with suboptimal doses: e.g. many multivitamin

preparations. Combinations with overdoses of drugs, e.g., some

paediatric anti-TB preparations, many multivitamin preparations

especially those containing Vitamin B12; many so-called iron tonics

with subtherapeutic doses of iron when iron deficiency anemia is a

most common deficiency. (See for instance, A Study on Drugs for

Treating Anaemia, DAF-K, Dharwar, 2006.)

v) Drug not licensed for a particular use but used for

unethical trials on human beings, mostly poor and illiterate.

(Example: Letrozole).

19. The Petitioners states and submits that according to the WHO

Expert Committee [see Use of Essential Drugs: Model List (Eleventh

List). World Health Organization, Geneva, 1999] combination drugs

should not be used unless there are no alternative single drugs

available for treatment or no alternative single drug was cost-

effective for the purpose. Experts recommend that patients be

individually evaluated and those patients requiring more than one

drug should be prescribed separately. Combination drugs ¡§increase

the risk of side-effects and may also needlessly increase cost while

encouraging irrational ¡¥miss and hit¡¦ therapy.¡¨ [beardshaw, V.

Prescription for Change. Penang: IOCU/HAI, 1983. pp.19.] When a

combination drug is used it is difficult to identify which of the

constituent drugs is the cause of a drug reaction. Combination drugs

are irrational also because their stability is doubtful, reducing

the efficacy in many preparations. Moreover, drug companies

frequently change the ingredients making it difficult to

- 11 -

keep track of the changes. [Every issue of MIMS India gives a list

of irrational combinations. For a more wide-ranging lists, the same

can be seen: Mira Shiva and Wishvas Rane. Banned and Bannable Drugs.

VHAI, New Delhi, 2004.]

20. The Petitioners herein reproduce below some relevant

extracts from WHO publications that have commented on the necessity

and relevance of FDCS; notably the periodically issued Reports of

the WHO Expert Committees on the Use of Essential Drugs:

¡§Most essential drugs should be formulated as single compounds.

Fixed-ratio combination products are acceptable only when the dosage

of each ingredient meets the requirements of a defined population

group and when the combination has a proven advantage over single

compounds administered separately in therapeutic effect, safety or

compliance.¡¨

[source: The Use of Essential Drugs: Ninth Report of the WHO Expert

Committee (WHO/EDM, 2000). Also in: World Health Organization

(1997). The Use of Essential Drugs. Seventh Report of the WHO

Expert. TRS 867.]

¡§It was noted that fixed-dose combinations offer certain advantages;

they facilitate adherence to treatment regimens and they can delay

the emergence of antimicrobial resistance. It was also noted that

many illogical and ad hoc combinations of various medicines are

currently being marketed in a number of countries. Any proposal to

include fixed-dose combinations in the Model List should be backed

by adequate proof of pharmaceutical compatibility and

bioavailability. In light of these comments, the Committee

recognized that its selection criteria with regard to fixed-dose

combination products were in need of review and recommended that

they be modified as follows:

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¡§Most essential medicines should be formulated as single compounds.

Fixed-dose combination products should be selected only when the

combination has a proven advantage in therapeutic effect, safety,

adherence or in decreasing the emergence of drug resistance in

malaria, tuberculosis and HIV/AIDS.¡¨

[source: WHO Expert Committee on the Selection and Use of Essential

Medicines (12th: 2002: Geneva, Switzerland). The selection and use

of essential medicines: report of the WHO Expert Committee, 2002:

(including the 12th model list of essential medicines). (WHO

technical report series; 914). Also in: WHO Expert Committee on the

Selection and Use of Essential Medicines (14th: 2005: Geneva,

Switzerland). The selection and use of essential medicines: report

of the WHO Expert Committee, 2005: (including the 14th model list of

essential medicines). (WHO technical report series; 933), page 57.]

21. A WHO manual for drug regulatory authorities has the

following to state about FDC¡¦s:

¡§New fixed-ratio combination products are regarded as new drugs in

their own right. They are acceptable only when (a) the dosage of

each ingredient meets the requirements of a defined population

group, and ( the combination has a proven advantage over single

compounds administered separately in terms of therapeutic effect,

safety or compliance. They should not be treated as generic

versions.

[World Health Organization. Marketing Authorization of

Pharmaceutical Products with Special Reference to Multisource

(generic) Products: A Manual for a Drug Regulatory Authority.

WHO/DMP/RGS/98.5 (1998)].

22. Elsewhere a WHO publication states circumstances when FDCS

are disadvantageous:

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„X ¡§FDCs discourage separate titration of each active

ingredient. This is a particular problem when both of the active

ingredients require dose titration. Indeed, it can be argued that

the very existence of an FDC discourages adjustment of doses to the

patient¡¦s needs (if that is appropriate for the combination in

question).

„X When the active ingredients in question have different

pharmacokinetics and/or pharmacodynamics, an FDC may not be

appropriate.

„X Unless both of the active ingredients are available as

separate entities, FDCs encourage polypharmacy irrespective of

whether it is appropriate for a particular patient. ¡§

[source: Regulation of fixed-dose combination products, WHO Drug

Information, Vol 17, No. 3, 2003] (Emphasis petitioners¡¦)

23. The Applicant states that the guidelines as per the WHO

recommendations for acceptability of Fixed Dose Combinations are:

a) Clinical documentation justifies the concomitant use of more

than one drug.

Therapeutic effect is greater than the sum of the effect of

each.

c) The cost of combination product is less than the sum of

individual products.

d) Compliance is improved (that is when two or more medicines

are to be taken separately, as in the case of TB, the user tends to

avoid one or two medicines after sometime. This can be avoided if

all three medicines are combined into one).

e) Sufficient drug ratios are provided to allow dosage

adjustments satisfactory for the majority of the population.

24. The Petitioners vehemently states that any fixed dose

combination, which does not satisfy the above-mentioned guidelines,

should be considered irrational.

- 14 -

25. The petitioners are aware of the necessity of FDCs in some

select circumstances. Indeed out of the total number of 347

essential drugs mentioned in the latest list of essential medicines

by WHO (March 2007), only 26 (7.5 %) are acceptable fixed dose

combinations. These cover FDCs for AIDS, TB, malaria, ORS, Iron plus

folic acid for anemia, trimethoprim + sulphamethoxazole (Brand

names: Bactrim/Septran), etc. The list of rational, acceptable FDC¡¦s

is given below for easy reference:

List of FDCs in WHO Essential Drug List March 2007

1. Amoxicillin + Clavulanic Acid

2. Artemether + Lumefantrine

3. Benzoic Acid + Salicylic Acid

4. Efavirenz + Emtricitabine + Tenofovir

5. Emtricitabine + Tenofovir

6. Ethinylestradiol + Levonorgestrel

7. Ethinylestradiol + Norethisterone

8. Ferrous Salt + Folic Acid

9. Imipenem + Cilastatin

10. Intraperitoneal Dialysis Solution (of Appropriate

Composition)

11. Isoniazid + Ethambutol

12. Levodopa + Carbidopa

13. Lidocaine + Epinephrine (Adrenaline)

14. Lopinavir + Ritonavir (LPV/R)

15. Medroxyprogesterone Acetate + Estradiol Cypionate

16. Neomycin Sulfate + Bacitracin

17. Oral Rehydration Salts

18. Rifampicin + Isoniazid

19. Rifampicin + Isoniazid + Ethambutol

20. Rifampicin + Isoniazid + Pyrazinamide

21. Rifampicin + Isoniazid + Pyrazinamide + Ethambutol

22. Stavudine + Lamivudine + Nevirapine

23. Sulfadoxine + Pyrimethamine

24. Sulfamethoxazole + Trimethoprim

- 15 -

25. Zidovudine + Lamivudine

26. Zidovudine + Lamivudine + Nevirapine

26. Thus drug combinations in some cases are not only rational

but are sometimes even necessary. To paraphrase the WHO criteria

mentioned above, FDCs are rational only when:

a) It allows synergistic action, i.e., it facilitates each

other¡¦s pharmacological action, thereby producing greater effects,

e.g., combined contraceptive pill, ORS, Calcium with Vitamin D.

It allows enhanced efficacy without disturbing each other¡¦s

pharmaco-chemical actions: e.g., when the combination lignocaine

with adrenaline increases the range and duration of action.

c) Combined doses are given in cases of general under-

nourishment or simultaneous deficiency of all vitamins in famine

conditions, e.g., Vitamin B complex, multivitamin, ferrous sulfate +

folic acid, Vitamin A + Vitamin D.

d) It is necessary to reduce side-effects or toxicity, e.g.,

isonex + Vitamin B6 (Vitamin B6 prevents peripheral neuritis caused

by prolonged use of isonex).

e) When two or more medicines are needed in invariable

proportion - e.g. iron-folic acid or when two or more medicines are

always required to be given together- for example ¡V isonex plus

rifampicin to reduce the chances of development of drug resistance.

27. The examples of broad categories of irrational drug

combinations include

- 16 -

„X Fixed Dose Combinations (FDCs) of Antibiotics and/or

Antimicrobials and Antidiarrhoeals

Antibiotics combined with other antibiotics or with cortico-steroids

or other active substances such as vitamins. Antibiotics with

antidiarrhoeals.

„X FDCs of Analgesics with Analgesics/Antiinflammatory drugs

The only analgesic combination which has been proved to be superior

to a single ingredient is aspirin plus caffeine. But in India nobody

markets it. All others are unjustified. - e.g., ibuprofen +

paracetemol or diclofenac + paracetemol. Combinations of two or more

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs, eg. Ibuprofen,

Diclofenac, Piroxicam, Azapropazone) increase the risk of toxicity

and other side-effects, especially kidney damage. Then there are a

whole lot of irrational combinations with nimesulide, itself a

hazardous drug that needs to be banned from India.

„X Analgesics combination with other medicines

Analgesics combined with iron, vitamins or alcohol. Combination

painkillers increase the risk of toxicity and other side-effects,

especially kidney damage. Analgesics combined with iron or vitamins

are irrational and wasteful; analgesics combined with alcohol are

wasteful and potentially dangerous.

„X Iron Preparations

Only preparations containing iron and folic acid and B12 (in

appropriate amounts) are rational and recommended by WHO. Only such

preparations need to be allowed. All other combinations purporting

to be iron syrups/tonics are irrational.

„X Cough Suppressants, Expectorants and Mucolytics

Combinations containing so-called expectorants like iodides,

chlorides, bicarbonates, acetates, squill, guiaphenesin, creosotes

and volatile oils

- 17 -

in addition to central cough suppressants, antihistaminics,

bronchodilators and mucolytics.

„X Oral Enzymes and Digestives

o Oral Enzymes for proteolytic and anti-inflammatory action,

i.e., trypsin, chymotrypsin, serrati peptidase, etc.

o Oral Digestive Enzyme Preparations of Pancreatin, Diastase

and Taka diastase, Papain, etc. (Though fixed dose combination of

Pancreatin or Pancrelipase containing amylase, protease and lipase

with any other enzyme are banned since 2000, some of the

combinations mentioned here are still available.)

„X Codeine in combination with other medicines:

Codeine is a habit-forming drug and using it in combination

medicines increases the risk of addiction.

„X ¡§Multi¡¨ and liquid vitamin preparations

With the exception of combination vitamins supplied in small

bottles, with droppers for babies.

„X FDCs of Antiasthmatic Drugs

„X FDCs of Antacids (other than magnesium hydroxide and

magnesium trisliciate)

„X Topical Anticoagulants

„X Oral/Injectable Haemostatics except Vitamin K

„X So-called Cerebral Activators such as Pyritinol and

Piractecam (Torrent)

„X Placentrex and products based on human/animal placenta

„X Ginseng and other such so-called sexual rejuvenators

„X Presence of Alcohol not required as solvent

„X Entire categories of products under the so-called label of

Nutritional Supplements.

- 18 -

„X Drugs (of non-modern medical systems) approved by the State

FDAs purporting to cure snake bites, increase semen, increase the

risk of abortion, increase fertility, brain tonics, etc.

Single ingredient drugs with side effects like sildenafil (Viagra)

to be marketed for only restricted conditions unlike at present.

28. From the above the Petitioners state that clear and

comprehensive criteria definition by DCGI/DTAB for withdrawal of

drugs and their fixed dose combinations (FDC¡¦s) from the Indian

market so that the withdrawal is not piece meal.

29. There has to be a complete withdrawal of irrational,

hazardous and useless, inessential drugs and their FDC¡¦s from the

Indian market on the basis of the above criteria. (What is

hazardous, that is with unacceptable risk/benefit ratio, useless and

non-essential, is also by definition irrational.). Strict adherence

to widely accepted principles of allowing FDC¡¦s (like the WHO

guidelines cited above) and not a selective, superficial exercise as

is being done at present that leaves room for all kinds

of ¡§negotiations¡¨ with industry. The DCGI has rejected certain drug

combinations because of inadequate supportive data. This gives the

impression that they are not irrational per se and they will be

allowed once the supportive data is provided. We say that as per

principles enumerated above, most of them, around 95 % of them, are

irrational and hence should not be licensed for sale and manufacture

in India. The DCGI be therefore restrained from authorising their

reentry in the market by allowing companies to produce ¡§suitable¡¨

data. Specification clearly of any combination of an irrational drug

as also irrational. That is if FDC (A+ is asked to be withdrawn

for reasons of irrationality, drug (A+ B+C), where C may be a

harmless drug, should also be considered irrational. That is no

loopholes and escape hatches be allowed to remain in the orders as

in the past. Only those drugs must be considered rational that are

mentioned in the standard medical and pharmacological textbooks and

have passed the scrutiny of approved medical journals ¡V a list that

would as a matter of course include lists like the WHO Model List

(revised March 2007) and the FDC¡¦s mentioned therein. All other

irrational, non-essential drugs including irrational, non-

essential FDC¡¦s

- 19 -

should be withdrawn from the Indian market. New FDC¡¦s not in the

standard textbooks should be licensed for marketing and manufacture

only after doing comparative trials that show superior therapeutic

advantages and higher benefit/risk ratio over single ingredient

alternatives. It is important that only rational FDC¡¦s in specified

presentations (e.g., tablet, liquid, injection) and strengths be

allowed. Other presentations and dosages should be considered

irrational. In terms of withdrawal strategy, the irrational drugs in

the top-selling 300 drugs of India should be immediately withdrawn.

Or in lieu the DCGI be asked to produce on what scientific evidence

(data of clinical trials, safety studies etc.) have they been

licensed for sale in India?

30. India¡¦s pharmaceutical industry has been manufacturing and

marketing fixed dose combinations (FDC¡¦s), many of them irrational

and harmful for the last two decades. Initially not many in number,

today they are in several thousands and a large number of them have

no therapeutic rationale.

31. Leading to the uncontrolled growth of FDC¡¦s is the pressure

of competition and new products. Responding to the pressure for

newer products, marketing heads of pharma companies invent

combinations of two or more drugs, often launching them without an

assessment of their therapeutic benefits. Technically FDC¡¦s are

considered new drugs.

32. The Union Health Ministry amended the Drugs & Cosmetics

Rules in 1988 to address this new development. Rule 122 (E) © of

the Drugs & Cosmetics Rules, says all new drugs have to be approved

by the Drug Controller-General of India (DCGI) for marketing in the

country after submission of all relevant pre-clinical and clinical

trial data.

33. The amendment makes it clear that the State drug authorities

have no power to issue product licences for FDC¡¦s. Most of the drug

control departments in the States and Union Territories in any case

do not have the expertise or facilities to assess the merits and

demerits of drug combinations. The 1988 amendment is observed more

in the breach; State licensing authorities (SLA¡¦s) continue to

- 20 -

permit FDC¡¦s over the years without insisting upon the statutory

requirements of pre- clinical and clinical trials.

34. At the same time, the Central Drug control administration,

the office of DCGI do not take responsibility and act to check the

problem of irrational combinations (as the 1988 amendment arms it

with the required powers) and do almost nothing. Combinations

multiply in the market. In November 2001, the DCGI for the first

time issues directive to State Drug controllers expressly

prohibiting them from issuing any more licences for combination

drugs; state drug control departments continue to ignore the DCGI

order.

35. In July 2004, the DCGI asks the State drug controllers to

withdraw all manufacturing licences issued by them for drug

combinations after May 2002. That directive too is ignored.

36. Meeting held in July 2007 of the Drug Consultative Committee

composed of MPs, Health ministry and DGCI officials and reviews the

problem of irrational combinations (nearly two decades after the

amendment that armed the DGCI with powers to check FDC¡¦s).

37. On August 14, 2007, DCGI once again issues a directive to

the State drug controllers asking them to start preparing for the

removal of irrational combinations from the market. The decision was

based on the studies of NPPA, Indian Drug Review, MIMS and CIMS.

Most State Drug controllers ignored the directive. The DCGI letter

directed the State Drug controllers to withdraw licences to such

products which were licensed by state drug controllers and not

approved by the DCGI, products which were licensed by State Drug

controllers and approved by DCGI since 1971, applications which were

approved by State Drug controllers but rejected by DCGI for

insufficient information and the products which were banned by drug

controllers but are reportedly available in the market.

38. On October 26-27, 2007, the DCGI meets state drug

controllers and industry representatives in Chandigarh. A list of

294 combinations was prepared

- 21 -

and classified into different categories based on their

irrationality and absurdity with the help of 100 pharmacologists.

The DGCI list of irrational products spans major therapeutic

categories such as orthopaedics, anti microbial, gastrointestinal

and cardiovascular.

39. In orthopaedics alone, there are more than 360 products

marketed by top companies such as Dr Reddy¡¦s, Alkem, Zydus Cadila,

Cadila Pharma, Piramal, Lupin, Glenmark and others. Most of

these combinations are of Chlorzoxazone, paracetamol and Diclofenac

sodium or ibuprofen.

40. In the gastrointestinal category, there are 248 irrational

products marketed by the same set of companies and others such as

Alembic, Ipca, Emcure, Cipla, Intas, Micro, Unichem and Merck. In

this category, a large number of products are of ofloxacin and

tinidazole or metronidazole.

41. There are also 200 anti-microbial products classified as

irrational belonging to again the same set of companies along with a

number of medium and small enterprises.

42. Pharma industry leaders oppose the DCGI¡¦s stand. A joint

memorandum of all the major Pharma Associations to the Union

Ministry of Health was given. It points out that the amendment of

the Drugs & Cosmetics Rules in 1988, the State Licensing Authorities

were required to obtain NOC¡¦s from the DCGI before issuing

manufacturing licenses for new FDC¡¦s. But, the SLAs ignored this

stipulation and continued to grant manufacturing licences for

combination products. Associations say the office of the DCGI was

fully aware of this above wrong practice. Some SLA¡¦s had even

brought the matter to the notice of the successive DCGI¡¦s, but they

had all ignored the alerts thus tip-toeing around the rule.

Therefore the office of DCGI is also responsible for the current

state of affairs and he should, therefore, give industry sufficient

time in this matter.

43. On November 1, 2007, the DCGI allowed selling of 150 'under

examination' FDC¡¦s lying with retailers till expiry.

- 22 -

1. On November 11-30, 2007, this Hon¡¦ble Court stayed the DCGI

letter and has thereby enabled the irrational FDC Drugs to prevail

in the market.

2. DCGI approved many drugs without safety trials. Cipla's i-

pill is not an exception; the office of the Drug Controller General

of India (DCGI) allowed several other drugs including Letrozole (Sun

Pharma's fertility drug) and Nimesulide for pediatric use (marketed

by Panacea Biotech) without the data provided to the regulatory

authority by respective Companies to ensure that the drug is safe in

Indian population. Both, the Canadian drug regulator and the

innovator company Novartis, had warned gynaecologists all over the

world not to use its brand 'Letoval' for female infertility. The

company had issued a warning saying, ¡¥The drug may cause foetal harm

when administered to pregnant women.¡¦

3. Drugs can be approved without safety studies as per Schedule

Y of the Drugs and Cosmetics Act for reasons of strong public

interest and when there is enough international safety data

available. No such exigency existed for these drugs.

4. On December 2007, Professional associations like Indian

Medical Association (IMA), President Dr Ajay Kumar, states that they

have not received any communication either from the drug department

or from the pharma companies about the FDC issue. Many of them were

aware of the issue through press reports. Since there is no official

communication, they were going ahead with prescribing combination

drugs.

5. During November 2007-Jan 2008, there was press reports that

pharma industry ready for talks with DCGI again to ¡§amicably settle¡¨

the FDC issue.

6. In the meantime, the country¡¦s top drug makers including

Ranbaxy Laboratories Ltd, Cipla Ltd, Piramal India Ltd, Sun

- 23 -

Pharmaceutical Industries Ltd and several others, who sell these

combination drugs in at least 3,000 brands, say they have applied

for fresh licences from the Centre. (DCGI) Venkateswarlu said the

department has so far received 186 applications, of which 50 have

been already rejected due to inadequate documentation to prove the

quality and efficacy of the drugs.

7. On Jan 15, 2008, Pharma press reports pharma companies

resumed production of FDC drugs in small quantities.

8. The letter dated 14.08.2007 issued by the 2nd Respondent,

which is impugned in the present Writ Petition is only a

communication bringing to the knowledge of the State Drugs

Controllers the illegality committed by their Officers by not

getting permission from the 2nd Respondent. It is a procedural

irregularity before granting the licence committed by all State

Drugs Controllers. The impugned order do not banned or stopped the

sale of said drug as alleged by the Writ Petitioner. It is for the

State Drug Controller to initiate action as per law pursuant to the

said letter dated 14.08.2007. Hence the present Writ Petition is

premature and based on apprehensions. If the said drugs are in

accordance with the prevailing prescriptions and rules, it is not

necessary for the Writ Petitioner to shy away from submitting to the

scrutiny of the Office of the 2nd Respondent. On the contrary

failure to do so will prejudice the interest of the Public at large

and the consequences will be in calculable.

9. Since the interest of the public at large are bound to be

materially affected by the outcome of the proceedings before this

Hon¡¦ble Court, the Petitioners humbly submits that it would be in

the interest of justice that they be permitted to be impleaded as

Party Respondent and be supplied all the copies of the documents

filed by the parties in the aforementioned matter. The Petitioners

craves leave to file a detail affidavit with relevant documents for

the proper adjudication of the matter.

- 24 -

10. The Order of Interim Stay granted by this Hon¡¦ble Court is

liable to be vacated failing which the public at large will be

highly prejudiced and put to severe loss and hardship. The balance

of convenience lies in favour of the Petitioners and they have every

likelihood of succeeding their case.

11. That this application is bonafide and made in the interest

of justice.

In the facts and circumstances stated herein above it is Most

Respectfully Prayed that this Hon¡¦ble Court may be pleased to permit

the Petitioners herein to implead as Respondents 2 to 6 in

W.P.No.35844 of 2007 and thus render justice

It is therefore prayed that this Hon¡¦ble Court may be pleased to

vacate the stay granted in M.P.No.2 of 2007 in W.P.No.35844 of 2007

and thus render justice.

Solemnly affirmed at Chennai this the

day of March, 2008 and affixed his

Before Me,

signature in my presence.

Advocate ¡V Chennai.