Evolution of Indian Pharma Regulatory Framework

Till independence in 1947, India has been following or rather copy-pasting the British regulations, whether in the Drugs Act, 1940, the (Indian) Patents and Designs Act, 1911 or the Medicinal and Toilet Preparations Act, 1955 (which emerged from Prohibition Act and Narcotic Act). Even though the Drugs Act was passed by the Indian Parliament in 1940 and the Drug Rules became official in 1945, the effective implementation commenced only many years later, after independence in 1947. Most Indian companies were manufacturing extracts, tinctures and medicines which were ‘compounded’ in the Medical Practitioner’s clinic. The Drugs Act, 1940 was later amended to include cosmetics in late 60s and further amended to include Ayurvedic preparations in the 80s. The Indian drug laws and its administration is in the Concurrent List (There are three lists, Union list, State list and Concurrent List), this made the uniform implementation of the Drugs & Cosmetics Act, a big challenge in India. Even though, the Act and Rules for drug formulations were already in place during independence, the enforcement was extremely weak and slow in implementation. Drugs Control Administrations were set-up in or around 1955 to 1957 in Bombay State (Maharashtra and Gujarat), Mysore State (Karnataka) and Madras Presidency/ State etc.

Pharmacy Act, 1948 was the most important legislation post-independence. BV Patel, Drugs Controller of the Bombay province, ML Khorana, UDCT and KG Ananthanarayan, Haffkine Institute constituted the first pharmacy tribunal to formulate the pharmacy regulations. After Pharmacy Council of India and various State Pharmacy Councils were formed in the 1950s and 1960s, consequent to the linguistic division, the states of Maharashtra and Gujarat were born in 1960. Patel was transferred as the Director of Drugs Control in Gujarat and Dr MK Rangnekar became the Director of Maharashtra Drugs Administration. The states of Karnataka and Madras were born too. It is around this time that the implementation or enforcement of Drugs and Cosmetics Act, commenced in India. While the pharmaceutical industry in India was ‘formally’ born in West Bengal (during the days of Acharya PC Ray), with pharma companies such as Dr Paul Lohmann, Bengal Chemical, Bengal Immunity, Smith Stanistreet, Dey’s Medical and others. Bombay (Maharashtra) and Gujarat emerged as pharma pioneers during 1960 to 1970 period. While Haffkine Institute (vaccines) and Cipla were industry leaders in Bombay, Alembic, Sarabhai and Gujarat Pharmaceuticals took lead in pharma industry growth in the western region. It is noteworthy that the hand-holding, industry-friendly, problem solution approach of industries in Maharashtra and Gujarat helped the growth of pharma industry in western India. The role of Central Drugs Standard Control Organization (CDSCO) or the office of the Drugs Controller (India) in Delhi remained restricted to law making till the 1990s. Central Drugs Controller’s approaches being friendly to industry and State Drugs Control [later named as FDAs (Food and Drugs Administration], there were harmonious growth of the pharma industry in India, in spite of the ‘Concurrent Status.’

Amendments

Major amendments to the Drugs and Cosmetics Act, 1940 were incorporated over the years including Schedule M, Schedule Y etc. In early years, it was the regulators who used to take a lead in resolving quality related problems of the industry. For example, the ‘particulate matter’ in injections was a perennial problem which needed technical and technological solutions. The Drugs Administration under Dr Rangnekar, took the lead jointly with industry and professional associations like Indian Drug Manufacturers’ Association (IDMA), Indian Pharmaceutical Association (IPA) to conduct extensive workshops and lectures by experts (including overseas speakers) to resolve the problem, which was eventually eliminated completely. Regulatory agencies working closely in tandem with the industry, catalytically promotes the healthy quality growth of the industry. While we have come a long way as regards to the quality of the regulators at CDSCO/DCG(I) office, the non-uniformity at the state level of FDAs in the country is alarming. While the state level drugs control officers have formed an association, ‘The All India Drugs Control Officers’ Confederation (AIDCOC) and have opened www.drugscontrol.org, it is hoped that this initiative will help boost the standards of quality of medicines as well as the GMP in manufacturing industry and related supply/ distribution chain thereof.

While the Central Drug Administration has made steady progress from the times of Borkar to current team of Dr GN Singh, DCG(I) and the two Joint DCGIs, Dr VG Somani and Dr Eswara Reddy, more needs to be done to bring Indian regulatory set up to global standards. Dr Bangarurajan, Dy DCG(I) is contributing by working with industry on quality data integrity and other issues in the West Zone. Under the aegis of the CDSCO/DCG(I), separate divisions must be set up for (ex:) NCE/NME approvals, biosimilars, herbal and natural products, combinations (FDCs), NDDS, medical devices and of course clinical trials. Team of experts must be appointed in each divisions to interact with industry and provide guidance and assistance for them to contribute to the National Healthcare needs and global leadership of India in respective fields.

Patents

Coming back to patents, need for amending the Patents and Designs Act of 1911 was felt, post-independence. There was no modern medicines or packaged foods or basic fertilizers available in India, because everything was under patents and only available through imports. Various committees, including Parliamentary Committees were appointed, culminating in the Ayyangar Committee (1959 Report of Justice Rajagopala Ayyangar) Report which based itself on an earlier Swan Committee Report of 1948. The much lauded Ayyangar Committee’s 53 amendments proposed to the 1911 Act, was languishing for nearly 10 years.

The Bill for Patents Act amendment lapsed in Parliament more than once. All was quiet on the patent front for nearly 10 years. All was not well on the mortality/morbidity rates as well in the Indian population post-independence. It is then, that the famous landmark judgement by Justice Vimadalal was delivered in the Bombay High Court on July 11, 1968. While Hoechst had an Indian Patent No.58716 on Sulphonylureas (Tolbutamide), Unichem had launched Tolbutamide tablets (antidiabetic) in the otherwise starved Indian market. Unichem was injuncted and found to infringe the product patent of Hoechst. The large diabetic patient pool of India was once again denied access to affordable treatment as the ‘Hoechst’s Rastinon’ was beyond the reach of Indian public. Once the ‘hue and cry’ alerted the government of Indira Gandhi, she quickly formed a Parliamentary Select Committee (Atal Bihari Vajpayee was also a member) among other luminaries headed by Dr Susheela Nayyar, following which the Patent Amendment Bill was passed in the Parliament in 1970, followed by the Rules amendment in 1972. As per the amendments to Patent Act 1970, only process patents on Drugs, Foods and Chemicals were allowable. Product patents on these fields were not eligible to be granted. The rest was history. Indian Pharma Industry grew by leaps and bounds thereafter, by reverse-engineering, supported by IDPL (Indian Drugs & Pharmaceuticals Limited).  There were full supportive initiatives from the government, through Hathi Committee report implementation, ratio parameters (Bulk drugs to formulation ratios were fixed company-wise), import substitution incentives etc.

The Patents Act, 1970, which catalysed the growth of the Indian pharma during the 1970 to 1990 period, threatened the developed countries so much that they came up with the Dunkel Draft Treaty (post Uruguay Round) which led to the TRIPs Agreement (Trade-Related aspects of Intellectual Property Rights) and the transition from GATT to WTO, post globalisation and harmonisation. India had to consequently amend the Patents Act, 1970, first in 1995 (1999) to provide for transition provisions (mailbox for Product Patent Applications) followed the 2nd and 3rd Amendments in 2002/2003 and 2005 respectively. Patent term got enhanced uniformly to all fields of technology to 20 years on May 2003 (with retrospective effect for valid patents). Full-fledged product patent regime returned to India in 2005 leading to opening of flood gates to product patents and infringement litigations. The 10-year period of 2007 and 2017 has seen a large number of patent infringement suits, most of them in Delhi High Court. A large number of ex parte ad-interim injunctions were granted in pharma patent litigations between 2010 and 2016. The now famous ‘Gleevec’ case started in 2005 and was finally decided by Supreme Court in April 2013. The one and only compulsory licence grant on ‘Sorafenib’ to NATCO (against Bayer Nexavar) created severe backlash from developed Nations and Bigpharma (US in particular). The Patent Rules 2016 provides for ‘expedited examination’ facility, subject to conditions. Indian Intellectual Property offices have now become fully ‘online’ and have become substantially transparent. Other Acts and Rules relating to Biodiversity, Plant Varieties Protection Act, Trade Marks, Designs have all been promptly enacted and enforced by India. Major reforms in Narcotic Control provisions have also been enacted.

Meeting global standards

India is substantially on track to meet global standards on pharma regulatory framework. Major restructuring and revamping are in progress in areas such as biosimilars, FDCs, GMP and related areas including ICH, PICs, clinical trials, Schedule Y, Medical Devices and pharmacovigilance which could strengthen the regulatory systems in India. At a time when the industry leaders are being adversely impacted by the negative attitude of US FDA inspection audits, the industry need to take these challenges as opportunities for further upgradation and compliance. Close cooperation of Indian CDSCO/Office of DCG(I) with overseas regulators are helping to upgrade Indian quality and regulatory standards. However, these positive measures are bound to impact profits of market leaders due to the sandwiching effect from stringent squeeze of DPCO. MSME pharma manufacturers are bound to feel the pressures for compliance to higher level, matching International Standards of GMP (beyond WHO-GMP) and other regulations. The environment related pollution control issues under the aegis of the NGT (National Green Tribunal) is adversely impacting the growth of the Pharma API industry in India.

The silver lining among these clouds is that the entrepreneur-driven Indian pharma Industry is bound to ride on these challenges and emerge as a global pharma superpower in next 10 years, if not through ‘Make in India’ by ‘Make overseas’ route, since Indian pharma is now mastering the International regulatory compliance standards.