Revisiting the Generic Drugs Controversy: The MCI Circular

Revisiting the Generic Drugs Controversy: The MCI Circular Dr KK Aggarwal National President IMA The 2016 amended clause 1.5 of the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002 reads: "1.5 - Use of Generic names of drugs: Every physician SHOULD prescribe drugs with generic names legibly and preferably in capital letters and he/ she SHALL ensure that there is a rational prescription and use of drugs." MCI by a circular dated 21.04.2017 has reinstated that all the Registered Medical Practitioners under the IMC Act are to comply with the aforesaid provisions of the Regulations in its letter and spirit and has warned that any violation will attract disciplinary action by the concerned SMC/MCI. “Every physician” means all those who are registered with MCI or the State Medical Council. “Should” means discretional and not mandatory. “Prescribe drugs with generic names” means writing the chemical name of the drug. This is not synonymous with generic drugs. Remember there are two types of drugs: generic and patent drugs. If the clause meant patent drugs then doctors cannot write new-innovation drugs as they will be under patent for ten years. All new discoveries of ICMR, biotechnology department then will be out of the prescriptions. The purpose of writing generic name of the drug is to reduce prescription errors due to multiple brands of the same drug. Branded drugs are drugs sold under a trade mark within the validity of patent life by the innovator or their licensee. Generic drug is the nomenclature of a drug adopted post expiry of its patent. It does not include the word “only’. If that was written, one could not write the brand or the name of the company. Than we could not have written Jan Aushadhi drugs. It does not mean that one can write only the generic names. Also, it does not prohibit a doctor from writing the name of the company or the brand or Jan Aushadhi. “Legibly” means readable (does not mandate electronic prescription) “Preferably” means where ever possible (it is non-mandatory) “In capital letters” (pertains to the chemical name, again non-mandatory as some names may be complicated or with very long salt name) “And he/ she shall ensure that there is a rational prescription and use of drugs”, use of the word “shall” means that this part of the clause is mandatory. Only this mandatory portion of the clause, with the word ‘SHALL’ can be actionable. “that there is a rational prescription and use of drugs", the prescription shall have rationality of treatment and the drugs prescribed. As per WHO, rational use of medicines requires that “patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period, and at the lowest cost to them and their community.

There is still confusion among doctors regarding the word “Generic”

There is still confusion among doctors regarding the word “Generic” Confusion still prevails among doctors as to what does the word “Generic” mean. I have tried to explain what is a generic drug as below. There are two types of drugs - patented or generic. The patented drugs are introduced in the market by the original company that researched the basic molecule. Let us take the example of Pfizer, which introduced two original molecules - Amlodipine and Sildenafil – and launched them in the international market as Amlogard (Amlodipine) and Viagra (Sildenafil). Being their research molecules, Pfizer had exclusive rights for 10 years based on their patent. These drugs are called patented drugs and the pharmaceutical company will have exclusive rights to them till the patent expires. After 10 years as the patent period expires, other companies can also market these molecules under their own brand name or as generic molecules. These are called non-patented generic version of the drugs. There is no difference by law in the quality of generic or patent versions of the drugs. For example, amlodipine in India is still available as Amlogard (Pfizer) @ Rs. 8/-; however, Dr. Reddy’s Lab also markets it as Stamlo, at less than Re.1/-. Similarly, Viagra (Sildenafil) was introduced @ Rs 600/- during the term of the patent, but the generic version is now available at less than Rs. 25/-. When we are asked to write generic name of the drug/s, this means that we should write the generic version of the drug/s and not the patented drug/s still marketed in India. Prescribing Amlogard or Viagra, when the generic Indian versions are available, cannot be justified. The generic version will be available at fraction of a cost than the patented versions. Let us take another example of the patented drug Clopidogrel, which is available as Plavix (original drug) and Deplatt, the Indian generic version. Plavix costs Rs.100/- and Deplatt Rs 5/-. Why write imported patented versions, when Indian generic versions are available. India is the largest exporter of generic versions of the drugs in the world as they can manufacture drugs at fraction of a cost compared to international brands. The word ‘Brand’ has nothing to do with the words ‘generic’ or ‘patented’ drugs. In India, generic versions of drugs can be sold in the name of molecule (generic-generic) or brand (generic-brand). The only thing that the Indian Medical Association (IMA) wants is that all generic versions of drugs in India should be permitted to be sold only at one price by one company. At present, the generic versions are being sold at three different prices (generic-generic, trade-generic and branded-generic) by the same company. Dr KK Aggarwal National President IMA & HCFI

We all prescribe generic drugs only, where is the confusion then? (Part 2)

We all prescribe generic drugs only, where is the confusion then? (Part 2) 15. Doctors are being blamed of writing only costly drugs? Quite often doctors are blamed of prescribing costly drugs to their patients. Every patient must know that convenience comes for a cost. The same drug molecule with same efficacy may cost more, if it gives you convenience. Remember cheap does not mean low quality or low efficacy. It’s like the basic model of a car, all accessories come for a price. The cost of a drug may vary depending on the following parameters • If the bitterness is removed • If it does not emit an odd smell • If it's aftertaste is better • If it looks soothing to the eyes due to specific shape or color • If the size of a tablet is small • If it is in a capsule form • If it provides instant relief • If it is to be used only once in day or it is a slow-, continuous- or delayed-release formulation • If the packing is better • If the preservative used is not sodium • If it does not contain any non-vegetarian ingredients • If it is in liquid formulation • If it uses nanotechnology • If it is a scored tablet • If it does not interfere with food • If it does not interfere with juices (grape) • If it is a combination of two or three drugs (as a single tablet) • If the drug is numbered in the strip (day-wise) • If the drug contains multiple drugs in the same strip so that the patient does not miss the dose • If it is not dispensed as loose tablets • The drug has not come out of a patent • If it is water soluble • If the drug salt granules are small or tiny • If it can be absorbed from the tongue • If it can be absorbed from the skin • If the drug-drug interaction is less • If it can be taken once a week or once a month • If the injection is with a prefilled syringe • If the injection is less painful • If the injection can be given directly in the vein vs in a drip • If the injection is in the form of a vial or single dose • If the shelf life of a drug is longer • Duration of action of a drug and its half life • If the difference between therapeutic dose and toxic dose is narrow • If it does not cause pill-induced esophagitis Pharmaceutical Prices in Selected Countries (Indian rupees) Drug India Pakistan Indonesia USA UK Ciprofloxacin 500 mg tabs 29.00 423.86 393.00 2352.35 1186.70 Norfloxacin 400 mg tabs 20.70 168.71 130.63 1843.56 804.78 Ofloxacin 200 mg tabs 40.00 249.30 204.34 1973.79 818.30 Cefpodoxime Proxetil 200 mg tabs 114.00 357.32 264.00 1576.58 773.21 Diclofenac Sodium 50 mg tabs 3.50 84.71 59.75 674.77 60.96 Ranitidine 150 mg tabs 6.02 74.09 178.35 863.59 247.16 Omeprazole 30 mg caps 22.50 578.00 290.75 2047.50 870.91 Lansoprazole 30 mg caps 39.00 684.90 226.15 1909.64 708.08 Source: Joint submission made by Indian Drug Manufacturers Association (IDMA) and Organisation of Pharmaceutical Producers of India (OPPI). 16. What are the recommended trade margins in NLEM medicines? As regards trade margins, the Sindhu Committee has said that the present norms for Scheduled Drugs should continue i.e. 8% for wholesalers and 16% for retailers (24%) In case of non-Scheduled Drugs, the recommended trade margins are 10% for wholesalers and 20% for retailers for the branded category of drugs (30%) and higher margins of 15% and 35% for wholesalers and retailers respectively for the generic drugs (50%). These margins would be inclusive of various trade discounts offered by industry to dealers. 17. What is the MCI mandate on writing generic version of a drug? The 2016 amended clause 1.5 of the Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations, 2002 reads: "1.5 - Use of Generic names of drugs: Every physician SHOULD prescribe drugs with generic names legibly and preferably in capital letters and he/ she SHALL ensure that there is a rational prescription and use of drugs." MCI by a circular dated 21.04.2017 has reinstated that all the Registered Medical Practitioners under the IMC Act to comply with the aforesaid provisions of the Regulations in its letter and spirit and has warned that any violation will attract disciplinary action by the concerned SMC/MCI. Interpretation • Use of Generic names of drugs: Means the chemical name of the drug o Every physician means all registered with MCI/SMC o ‘Should” means discretional and not mandatory o Prescribe drugs with generic names means writing the chemical name of the drug o Legible: means readable (does not mandate electronic prescription) o And preferably (where ever possible and is non-mandatory) • in capital letters (pertains to the chemical name, again non-mandatory as some names may be complicated or with very long salt name) o It does not include the word “only’, so it does not mandate against writing the name of the brand, company or Jan Aushadhi. o And he/ she shall ensure that there is a rational prescription and use of drugs: means this part of the clause is mandatory (shall) o Only this mandatory portion of the clause, with the word ‘SHALL’ can be actionable. o The prescription shall have rationality of treatment and the drugs prescribed. The non-mandatory initial part of the clause can-not lead to action by SMCs as it is discretionary. “should prescribe drugs with generic names”: It does not write only with generic names. It does not prohibit a doctor from writing the name of the company or the brand or Jan Aushadhi. o As per WHO, rational use of medicines requires that "patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period, and at the lowest cost to them and their community" 18. In clinical practice how do I choose the lowest cost drug, yet with quality assured? Choose from National list of Essential Medicines 2015: These 276 drugs are approved/licensed in India; for diseases which are a public health problem in India, are drugs with proven efficacy and safety profile based on valid scientific evidence and are made cost effective by capping their MRP. These medicines must be aligned with the current treatment guidelines for the disease. These medicines should be stable under the storage conditions in India. Finally, when more than one medicine is available from the same therapeutic class, preferably one prototype/ medically best suited medicine of that class to be included after due deliberation and careful evaluation of their relative safety, efficacy, cost-effectiveness. Price of total treatment is considered and not the unit price of a medicine. Fixed Dose Combinations (FDCs) are generally not included unless the combination has unequivocally proven advantage over individual ingredients administered separately, in terms of increasing efficacy, reducing adverse effects and/or improving compliance. If a medicine with better efficacy or favorable safety profiles and better cost-effectiveness is now available the previous drug will be taken out of the NLEM list. 19. Can you give one example of NLEM vs Non NLEM drug? Amlodipine, atenolol, enalapril maleate, losartan potassium, labetalol, methyldopa, ramipril, telmisartan, diltiazem, and hydrochlorothiazide are the medicines under NLEM for hypertension. Non NLEM drugs will be olmesartan and azilsartan. While the cost of losartan is Rs 1/- per tablet, that of azilsartan is Rs19/- per tablet. 20. Why do companies not promote NLEM drugs? NLEM drugs are price-capped and may not be viable for the company. To make profit, companies will always be in process of launching newer non-inferior Non NLEM drugs or NLEM drugs in combinations so they can come out of price capping. 21. Can we write non NLEM drugs? Yes, but it is always better to choose NLEM drug and while choosing a non- NLEM drug, inform the patient the reason you are prescribing a non-NLEM drug. 22. Can MCI mandate and change ‘should’ to ‘shall’? The main objective of MCI is to regulate and prescribe minimum standards in medical education and not deciding matters like usage of generic drugs with or without a brand name. 23. But the Hon’ble Prime Minister, Sh. Narendra Modi has said that the Government is contemplating a legislation that will make it mandatory for the registered medical practitioners to prescribe generic only drugs (without a brand name)? The Prime Minister’s concern is quality and most economical drug from Jan Aushadhi or otherwise. IMA, in principle welcomes this concern. But IMA is also equally concerned about the clinical efficacy of a drug. We have very serious concerns regarding quality assurance and other complex issues involved in drugs available in the market. India has more than 67,000 drug formulations but the quality control mechanism (Combined testing capacity of all the Central Drugs Testing Laboratories) can ascertain the quality of only 15753 drugs annually. A 2014 study showed that 10.9% of the random drugs samples tested were of poor-quality with 7 percent contained less than the required dosage of active ingredients and 3.9 percent without necessary active ingredients. One of the major reasons for number of deaths that had occurred in the sterilization camp held in Chhattisgarh was due to quality of drugs used. The verdict of the Chhattisgarh High Court also confirmed the deaths were due to sub-standard generic- generic drugs used during the operative course. A 2014 study showed that 10.9% of the random drugs samples tested were of poor-quality with 7 percent contained less than the required dosage of active ingredients and 3.9 percent without necessary active ingredients. 24. Why can’t we prescribe generic-only names? If we do that, then who will decide which companies salt to be given and who will take the legal responsibility if the clinical condition of the patient does not improve. Can the sales person in the medical store do that? The answer is big no. The right to choose a rational drug or a brand vests only with the Registered Medical Practitioner and not the chemist. Government should insist on the pharmaceutical manufacturers to market drugs under one drug- one price- one company policy. 25. What is the solution then? • The differential pricing of generic-generic, trade- generic or branded generic from the same company needs to be addressed. • Retailers have a strong financial incentive to push trade -generic drugs, even if doctors prescribe branded, as the margins to sell trade generics may be as high as 1000%. • There should be one price to the retailer and one price to the customer with fixed retailer margin. • The quality assurance of the generic-only pharmaceuticals needs to be assured. • For the marketing of generic only drugs including Jan Aushadhi, there should be an efficient and effective quality control mechanism where every batch of the drug is tested; uniform process of manufacturing; ensured bio-availability and bioequivalence; ensured storage conditions and shelf life and uniform price of generic drugs irrespective of their formats. • A generic manufacturer also needs to demonstrate that the marketed product contains the same active ingredients as the innovator product; is identical in strength, dosage formulation and route of administration to the innovator product; is bioequivalent to the innovator product; has the same clinical indications and meets the same batch requirements for identity strength, purity and quality. • The Government to achieve this should raise the expenditure on health to 2.5 % of GDP from the current abysmal 1.1%; implement Good Manufacturing (GMP) practices in drug industry; strengthen the quality control infrastructure to the required level so that the quality of every batch of drugs is tested and ensured; deploy adequate manpower to enforce the laws regarding drugs; stop the over the counter sale of prescription drugs without prescription; do not allow a company to market same drug in different prices under different brands; prevent quacks and alternative system from using modern medicine drugs and initiate awareness movement amongst doctors and patients on generic- generic drugs. 26. What is the IMA campaign? Write Salt name in CAPITAL: Write legible: Write brand in (bracket): Write NLEM, Write Non NLEM with consent: Choose Economical Brand of a standard company. The NLEM List is available at http://cdsco.nic.in/WriteReadData/NLEM-2015/NLEM,%202015.pdf There should be one price for the drug from one company whether it is sold as generic-only, trade-generic or brand-generic. 27. What were the IMA- FOMA resolutions? IMA FOMA Delhi Resolutions (Federation of Medical Associations) are as follows: • The judgement to choose a rational drug and its format vests only with the Registered Medical Practitioners. This right of the medical profession is sacrosanct. • IMA- FOMA also wants the Government to strengthen Quality control mechanisms to ensure adherence to Good Manufacturing Practices(GMP) whether generic or branded for patient safety. • For a rational prescription, doctors should choose drugs generic or branded based on quality, efficacy and economy and write legibly and preferably in capital letters. • IMA-FOMA recommends that Government should ban differential pricing of a drug under different brand names (generic - generic, trade generic or branded generic) by one company. (one chemical drug, one company, one price) IMA FOMA will be meeting the President of MCI, Union Health Minister and Prime Minister of India about the views of the medical fraternity on this issue. All the constituent members of IMA-FOMA shall communicate these IMA-FOMA Delhi Resolutions to its members. 28. What is your final quote? We the medical professionals are committed to the welfare and safety of patients. Quality followed by economy is our main concern and not the economy alone. Dr KK Aggarwal National President IMA

IMA lauds mandatory bioequivalence studies for drugs

IMA lauds mandatory bioequivalence studies for drugs Move will ensure that the manufactured drugs are safe and effective New Delhi, April 28, 2017: In what can be called a long overdue move, the Ministry of Health and Family Welfare, has made bioequivalence studies compulsory for all drugs before they are launched in the Indian market. The draft amendments were first advertised in early February for public comment. Following this, the Drugs and Cosmetics Rules, 2017 were formally amended through a notification on April 3 to incorporate the change. Bioequivalence studies are conducted to establish that both the original patented drug and a generic version of it have the same biological equivalence. This means they should work the same way, to the same extent, and for the same purpose. Welcoming this move, Padma Shri Awardee Dr K K Aggarwal, National President Indian Medical Association (IMA) and President Heart Care Foundation of India (HCFI) and Dr RN Tandon – Honorary Secretary General IMA in a joint statement, said, "For a long time, doctors have been prescribing generic drugs with no data on how these would perform. Until recently, only new drugs which have been in India for less than four years were required to undergo bioequivalence studies if they were in use in developed markets like the US and Europe. Many domestic manufacturers waited till the fifth year and got approval to manufacture and sell generics without conducting bioequivalence studies. However, IMA has always stood for conducting bioequivalence studies and the health ministry needs to be lauded for this decision." Bioequivalence studies are mostly conducted on a smaller group of healthy volunteers. On the other hand, clinical studies are conducted on patients who suffer from a said disease. The cost of a bioequivalence study is therefore only a small fraction of clinical trials. The amendment introduces a biopharmaceutical classification system, classifying drugs into categories based on solubility and permeability: i) category I- high solubility and high permeability; (ii) category II- low solubility and high permeability; (iii) category III- high solubility and low permeability; and (iv) category IV- low solubility and low permeability. Manufacturers will now need to conduct bio-equivalency studies on category II and IV drugs to obtain a manufacturing license from the state licensing authority. Adding further, Dr Aggarwal, said, "This decision is definitely a step in the right direction. It not only aligns the Indian framework with global standards but also ensures that the drugs manufactured are safe and effective. It assumes greater significance in light of the fact that doctors today are being asked to mandatorily prescribe generic drugs to consumers." The cornerstone for a vibrant public health framework is access to affordable and safe medicines. Future challenges may include ensuring that clinical research organizations conducting bioequivalence studies do not commit fraud.

Do not take drugs with juices

Do not take drugs with juices New Delhi, July 16, 2016: "Grapefruit juice can reduce the absorption of certain medications. Other common juices, including orange and apple, may limit the body’s absorption of drugs, compromising their effectiveness," said Padma Shri Awardee Dr KK Aggarwal – President Heart Care Foundation of India (HCFI) and Honorary Secretary General IMA. Quoting Dr David Bailey from the University of Western Ontario, Canada, Dr Aggarwal said that grapefruit juice markedly reduces the amount of drug that gets into the bloodstream. As per the American Academy of Family Physicians, doctors traditionally warn against drinking grapefruit juice if you’re taking certain medications for high cholesterol, high blood pressure, and heart rhythm problems. Research has shown that grapefruit juice, as well as orange and apple juice, can lower the body’s absorption of some drugs like anti-cancer drug Etopophos, beta-blockers like Atenolol, and anti-transplant rejection drug cyclosporine and antibiotics, including ciprofloxacin, levofloxacin, and itraconazole. Healthy volunteers who took the allergy drug fexofenadine with grapefruit juice absorbed only half the amount of the drug, compared with volunteers who took the medicine with water. Substances in the juices affect the absorption of drugs. Some chemicals block a drug uptake transporter, reducing drug absorption; other chemicals block a drug metabolizing enzyme that normally breaks down the drugs. In general, it’s safest to take medication with water. A glass is better than a sip. It helps dissolve the tablet. Cool water is better than hot because your stomach empties cool water faster, sending the medication on its way to the small intestine and finally the blood stream.

Do not take drugs with juices

Do not take drugs with juices New Delhi, July 16, 2016: "Grapefruit juice can reduce the absorption of certain medications. Other common juices, including orange and apple, may limit the body’s absorption of drugs, compromising their effectiveness," said Padma Shri Awardee Dr KK Aggarwal – President Heart Care Foundation of India (HCFI) and Honorary Secretary General IMA. Quoting Dr David Bailey from the University of Western Ontario, Canada, Dr Aggarwal said that grapefruit juice markedly reduces the amount of drug that gets into the bloodstream. As per the American Academy of Family Physicians, doctors traditionally warn against drinking grapefruit juice if you’re taking certain medications for high cholesterol, high blood pressure, and heart rhythm problems. Research has shown that grapefruit juice, as well as orange and apple juice, can lower the body’s absorption of some drugs like anti-cancer drug Etopophos, beta-blockers like Atenolol, and anti-transplant rejection drug cyclosporine and antibiotics, including ciprofloxacin, levofloxacin, and itraconazole. Healthy volunteers who took the allergy drug fexofenadine with grapefruit juice absorbed only half the amount of the drug, compared with volunteers who took the medicine with water. Substances in the juices affect the absorption of drugs. Some chemicals block a drug uptake transporter, reducing drug absorption; other chemicals block a drug metabolizing enzyme that normally breaks down the drugs. In general, it’s safest to take medication with water. A glass is better than a sip. It helps dissolve the tablet. Cool water is better than hot because your stomach empties cool water faster, sending the medication on its way to the small intestine and finally the blood stream.