RATIONAL vs IRRATIONAL: Fixed-dose combinations (FDCs), are combinations of two or more active drugs in a single dosage form. Drugs in a combination should be complementary in action; their side effects should not be overlapping; they should have a proven advantage over single drugs administered separately in efficacy, safety, and compliance. FDCs like the quadruple drug combination for TB and triple drug “cocktail” for AIDS are desirable. Fourteen FDCs found to lack therapeutic justification and some with additive adverse effects have been banned by the Central government recently. The sale of 344 FDCs, especially of painkillers, antibiotics, and vitamins, identified by the Central Drugs Standard Control Organisation (CDSCO) as irrational was banned in 2016. This has not deterred manufacturers from releasing new irrational FDCs that add to the cost and adverse consumer effects. Injudicious use of antibiotic FDCs has led to resistant strains of pathogens. Antipyretics that reduce fever by sweating are irrationally combined with antispasmodics that block sweating. Cough suppressants are combined with expectorants that induce coughing. Many such irrational FDCs and cough syrups sold over the counter are highly popular in India and used as self-medication, even when banned. An urgent clean-up of quackery and substandard drugs is needed.
ETHICAL PRACTICES vs EXPLOITATION: Reputed companies like Cipla, Dr. Reddy’s, Mankind, Alkem, and Intas, have to now withdraw their FDCs that were banned recently. Pharmatrac’s April data indicates a Rs 807 crore loss due to the ban on the 14 FDCs, of which Rs 770 crore (95%) is in respiratory drugs. 24 years ago Cipla received worldwide appreciation when it developed efficient methods for producing three anti-AIDS drugs and providing them at affordable prices. This played a stellar role in suppressing the AIDS epidemic. Yusuf Hamied, the chairman of Cipla has stated, “We are not making money, but we are not going to lose money either, since with the average of the three prices we should break even.” Efficient high-quality alternative drug production technologies have made Indian cancer drugs, antivirals, antibiotics, and other drugs affordable, available and popular globally and are extensively used by WHO, charitable organizations like British Oxfam, Doctors Without Borders, Bill & Melinda Gates Foundation for fighting infections like tuberculosis, filariasis, malaria. Global Times, the official Chinese English paper reported that Swiss pharmaceutical Novartis’s leukemia drug “Glivec”, costs US$3,783 (27,000 yuan) each month in China in contrast with Indian pharma Natco’s “Veenat”, which costs just 200 yuan. Pfizer’s Paxlovid, a combination of the anti-corona viral Nirmatrelvir with the anti-AIDS drug Ritonavir is in short supply and is far costlier than Indian generics Primovir and Paxista being smuggled into China. In sharp contrast, the lack of quality checks on exported cough syrups by two Indian companies led to WHO accusations about Diethylene glycol and Ethylene glycol impurities in Indian cough syrups causing the deaths of children in Gambia and Uzbekistan. We expect the pharma industry to follow ethical practices of quality manufacturing, rational choices, reasonable pricing, drug efficacy, and safety.
QUALITY ASSURANCE: Ideally, Indian pharma companies should self-regulate and ensure their products’ safety, efficacy, and affordability, to earn respect globally. A few bad apples can ruin the reputation of all Indian pharmaceuticals and also of other Indian exports. The Drugs and Cosmetics Amendment Act 2008 provides very strict and stringent penalties for the manufacture of spurious and adulterated drugs. 4.5% of all generic medicines in the Indian market were substandard as per a 2018 report of the CDSCO. Xylazine, a non-opioid veterinary tranquilizer, Fentanyl, a potent synthetic opioid drug, and narcotics are extensively being abused by addicts in the US and need urgent regulation. Many states do not have labs or qualified staff to ensure quality control. Most states have a shortage of drug inspectors as most of the vacancies have not been filled due to litigation or local political interference. Some of our states have combined food and drug safety regulations under one FDA. Dr Krishna Ella, Executive Chairman of Bharat Biotech has suggested a merger of all state FDAs with the Central Drugs Standard Control Organization to make it a uniform enforceable system. Both the CDSCO and the Food Safety and Standards Authority of India (FSSAI) are under the Ministry of Health & Family Welfare. A single Central food and drug regulations authority for the entire nation is desirable.
INNOVATE: The US has 6 six of the 10 largest pharmaceutical companies globally, accounting for 45% of global $1.6 trillion pharma revenue. R&D to discover new drugs and efficient drug manufacturing is essential for global leadership. Drug discovery software with artificial intelligence and machine learning can be used to discover a novel effective and safe therapeutic drug and then optimize its production and delivery. Sadly these can be also misused to discover toxins deadlier than nerve agent VX and Novichoks. Ethics, sustainability, and innovation are the bedrock of global leadership and need to be followed by all Indian industries to compete globally.
Dr P.S. Venkatesh Rao is Consultant Endocrine, Breast & Laparoscopic Surgeon in Bengaluru.