The Parliamentary Standing Committee on Health and Family Welfare tabled a Report in Parliament on May 8, 2012, on the functioning of the Central Drugs Standard Control Organization (CDSCO).  CDSCO is the agency mandated with the regulation of drugs and cosmetics in India.  The Report covers various aspects of drug regulation including organizational structure and strength of CDSCO, approval of new drugs, and banning of drugs, among others. Following the Report, the Minister of Health and Family Welfare has constituted a Committee to look into the procedure for drug regulation.  The Committee is expected to make its submissions within a period of two months. This post focuses on irregularities in the approval of new drugs by CDSCO.  It discusses the regulations relating to drug approval and the Standing Committee's observations on the working of CDSCO. Approval of new drugs Drugs are regulated by the Drugs and Cosmetics Act, 1940 and Drugs and Cosmetic Rules, 1945 [Rules].  The CDSCO, under the Ministry of Health and Family Welfare, is the authority that approves new drugs for manufacture and import.  State Drug Authorities are the licensing authorities for marketing drugs. New Drugs are defined as:

  • drugs that have not been used in the country before,
  • drugs that have been approved by a Licensing Authority but are now being marketed for different purposes, and
  • fixed dose combinations of two or more drugs that have been individually approved before but are proposed to be combined in a fixed ratio that has not been approved.

The Rules require an applicant for a new drug to conduct clinical trials in India to determine the drug’s safety and efficacy.  These trials are necessary for both domestically manufactured and imported drugs.  However, the authority can exempt a drug from the requirement of local and clinical trials in the public interest based on data available in other countries. Observations and recommendations of the Committee The Committee found that a total of 31 new drugs were approved between January 2008 and October 2010 without conducting clinical trials on Indian patients.  The Report mentioned that drug manufacturers, CDSCO officials and medical experts colluded to approve drugs in violation of laws.  Following are some of the Report’s findings:

  • Under the Rules, the Drugs Controller General (India) (DCGI), the head of CDSCO, can clear sites of clinical trials after ensuring that major ethnic groups are enrolled in these trials to have a truly representative sample.  This rule was violated by the DCGI when sites for clinical trials were approved without ensuring diversity.  The Committee recommended that the DCGI approve sites for trials only if they cover patients from major ethnic backgrounds.
  •  The Report found that certain actions by experts were in violation of the Code of Ethics of the Medical Council of India.  A review of expert opinions revealed that several medical expert recommendations had been given as personal opinions rather than on the basis of scientific data.  Additionally, many expert opinions were written by what the Report calls ‘the invisible hands’ of drug manufacturers.  The Committee recommended that CDSCO formulate a clear set of written guidelines on the selection process of experts with emphasis on expertise in the area of drugs.
  •  The Rules ban the import and marketing of any drug whose use is prohibited in the country of origin.  CDSCO violated this rule by approving certain Fixed Dose Combination drugs for clinical trials without considering the drugs’ regulatory status in their respective country of origin.  Drugs such as Deanxit and Buclizine, which have been prohibited for sale and use in their countries of origin, Denmark and Belgium, respectively, were approved for clinical trials.  The Committee recommended an inquiry into the unlawful approval of these drugs.
  • The Rules require animal studies to be conducted for approval of a drug for use by women of reproductive age.  CDSCO violated this rule in approving Letrozole for treating female infertility.  Globally the drug has only been used as an anti-cancer drug for use among post-menopausal women.  The drug has not been permitted for use among women of reproductive age because of side effects.  The Committee recommended that responsibility be fixed for unlawfully approving Letrozole.
  •  Rules require Post-marketing Safety Update Reports (PSURs) on drugs to be submitted to CDSCO.  PSURs are used to collect information on adverse effects of drugs on Indian patients as a result of ethnic differences.  When asked by the Committee to furnish PSURs on 42 randomly selected new drugs, the Ministry was able to submit PSURs for only 8 drugs.  The Report contended that this action reflected a poor follow-up of side effects on Indian patients.  The Committee recommended that manufacturers of new drugs be warned about suspension of marketing approval unless they comply with mandatory rules on PSURs.

Our Constitution provides protection against laws imposing criminal liability for actions committed prior to the enactment of the law. Article 20 (1) under the Part III (Fundamental Rights), reads: 20. (1) No person shall be convicted of any offence except for violation of a law in force at the time of the commission of the act charged as an offence, nor be subjected to a penalty greater than that which might have been inflicted under the law in force at the time of the commission of the offence. Thus, the maximum penalty that can be imposed on an offender cannot exceed those specified by the laws at the time. In the context of the Bhopal Gas tragedy in 1984, the Indian Penal Code (IPC) was the only relevant law specifying criminal liability for such incidents. The CBI, acting on behalf of the victims, filed charges against the accused under section 304 of the IPC (See Note 1). Section 304 deals with punishment for culpable homicide and requires intention of causing death. By a judgment dated September 13, 1996, the Supreme Court held that there was no material to show that “any of the accused had a knowledge that by operating the plant on that fateful night whereat such dangerous and highly volatile substance like MIC was stored they had the knowledge that by this very act itself they were likely to cause death of any human being.” The Supreme Court thus directed that the charges be re-framed under section 304A of the IPC (See Note 2). Section 304A deals with causing death by negligence and prescribes a maximum punishment of two years along with a fine. Consequently, the criminal liability of the accused lay outlined by section 304A of the IPC and they were tried accordingly. Civil liability, on the other hand, was adjudged by the Courts and allocated to the victims by way of monetary compensation. Soon after the Bhopal Gas tragedy, the Government proposed and passed a series of laws regulating the environment, prescribing safeguards and specifying penalties. These laws, among other things, filled the legislative lacunae that existed at the time of the incident. Given the current provisions (See Note 3), a Bhopal like incident will be tried in the National Green Tribunal (once operationalized) and most likely, under the provisions of the the Environment (Protection) Act, 1986. The criminal liability provisions of the Act (See Note 4) prescribe a maximum penalty of five years along with a fine of one lakh rupees. Further, if an offence is committed by a company, every person directly in charge and responsible will be deemed guilty, unless he proves that the offence was committed without his knowledge or that he had exercised all due diligence to prevent the commission of such an offence.

The civil liability will continue to be adjudged by the Courts and in proportion to the extent of damage unless specified separately by an Act of Parliament.

Notes 1) IPC, Section 304. Punishment for culpable homicide not amounting to murder Whoever commits culpable homicide not amounting to murder shall be punished with imprisonment for life, or imprisonment of either description for a term which may extend to ten years, and shall also be liable to fine, if the act by which the death is caused is done with the intention of causing death, or of causing such bodily injury as is likely to cause death, Or with imprisonment of either description for a term which may extend to ten years, or with fine, or with both, if the act is done with the knowledge that it is likely to cause death, but without any intention to cause death, or to cause such bodily injury as is likely to cause death. 2) IPC, Section 304A. Causing death by negligence Whoever causes the death of any person by doing any rash or negligent act not amounting to culpable homicide, shall be punished with imprisonment of either description for a term which may extend to two years, or with fine, or with both. 3) Major laws passed since 1984: 1986 - The Environment (Protection) Act authorized the central government to take measures to protect and improve environmental quality, set standards and inspect industrial units. It also laid down penalties for contravention of its provisions. 1991 - The Public Liability Insurance Act provided for public liability - insurance for the purpose of providing immediate relief to the persons affected by an accident while handling hazardous substances. 1997 - The National Environment Appellate Authority Act established to an appellate authority to hear appeals with respect to restriction of areas in which any industries, operations or processes are disallowed, subject to safeguards under the Environment (Protection) Act, 1986. 2009 - The National Green Tribunal Act, yet to be notified, provides for the establishment of a tribunal for expeditious disposal of cases relating to environmental protection and for giving relief and compensation for damages to persons and property. This Act also repeals the National Environment Appellate Authority Act, 1997. 4) Criminal liability provisions of the Environment Protection Act, 1986 Section 15. Penalty for contravention of the provisions of the Act (1) Whoever fails to comply with or contravenes any of the provisions of this Act, or the rules made or orders or directions issued thereunder, shall, in respect of each such failure or contravention, be punishable with imprisonment for a term which may extend to five years with fine which may extend to one lakh rupees, or with both, and in case the failure or contravention continues, with additional fine which may extend to five thousand rupees for every day during which such failure or contravention continues after the conviction for the first such failure or contravention. (2) If the failure or contravention referred to in sub-section (1) continues beyond a period of one year after the date of conviction, the offender shall be punishable with imprisonment for a term which may extend to seven years. Section 16. Offences by Companies (1) Where any offence under this Act has been committed by a company, every person who, at the time the offence was committed, was directly in charge of, and was responsible to, the company for the conduct of the business of the company, as well as the company, shall be deemed to be guilty of the offence and shall be liable to be proceeded against and punished accordingly: Provided that nothing contained in this sub-section shall render any such person liable to any punishment provided in this Act, if he proves that the offence was committed without his knowledge or that he exercised all due diligence to prevent the commission of such offence.