Drug Regulation

Special Report: The Judicial and Policy Quackery Behind the Regulatory Restrictions on Oxytocin


Long read

There has been panic and alarm amongst doctors, especially gynecologists, since the announcement by the Ministry of Health & Family Welfare (MOHFW) on June 27, 2018 that only one public sector undertaking, Karnataka Antibiotics & Pharmaceutical Ltd. (KAPL) would be authorized to manufacture and supply oxytocin for the Indian market from July 1, 2018. The drug oxytocin is considered a critical hormone for maternal healthcare since it is used for inducing labour and more importantly, to control bleeding during labour, which can otherwise be a cause of death amongst young Indian women who tend to be anemic.

While several media reports reported the restricted manufacturing order as being announced only on June 27, the order restricting manufacture of oxytocin was issued on April 27, 2018. This strangely worded order, which was issued under Section 26A of the Drugs & Cosmetics Act, forbade the private sector from manufacturing this drug for the Indian market while still allowing them to manufacture for the purposes of exporting the hormone manufactured in India. Limiting the manufacture to only one public sector undertaking understandably caused panic amongst the medical community because the government was basically disrupting an entire market dominated by the private sector and could lead to potential shortages. Given that India has a population of 1.3 billion people, it is doubtful if just one company can meet the demand of the entire nation. It is perhaps for this reason that the government has pushed the deadline to September 1.

The background of the events leading to this order is a perfect illustration of the quackery that passes off as health policy in this country.

The court of its own motion, the amicus & the absence of evidence

The government order dated April 27 begins with the observation that the High Court of Himachal Pradesh in the case of ‘Court on its motion v. State of Himachal Pradesh’, had observed that “there is large scale clandestine manufacture and sale of the drug Oxytocin leading to its grave misuse, which is harmful to animals and humans” and that it had ordered the government to consider the feasibility of restricting the manufacturing of Oxytocin to only the public sector.

A reading of the High Court’s order delivered by a bench of Chief Justice Mansoor Ahmad Mir & Justice Tarlok Singh Chauhan reveals that the judges took up this issue of alleged misuse of oxytocin, on November 24, 2014 after they read a news item published in daily Hindi vernacular Amar Ujala alleging the “illegal use of lethal vaccine Oxytocin on fruits, vegetables and animals”. In reality, Oxytocin is not a vaccine but a hormone, naturally produced by the human body. The most common allegation, which has also been made in Parliament, by animal activists, like the incumbent Minister for Child Development Maneka Gandhi, is that Oxytocin is misused by dairy farmers to induce labour in cattle so as to force their bodies into producing milk.

 As if often the case with such public interest litigations, the high court appointed a senior advocate as amicus curiae to assist the court. The court records that the amicus curiae had “painstakingly” placed on record material demonstrating the supposedly rampant and widespread misuse of Oxytocin on milch animals, fruits and vegetables which was harmful to not just the animal but also on humans who drank the milk of these animals. The judgment records the following as the possible effects of Oxytocin on the human body:

“The Oxytocin not only effects the cow/buffalo, it filters into the milk and consequently, has been held responsible for breast and uterine cancers, male impotence, excessive hair on woman and balding for men, early or erratic periods, early development of breasts (in both sexes). Its use is also considered harmful eyes, especially in children. The hormone affects the reproductive ability of woman. Its most common symptoms are exhaustion and loss of energy. Consumption of Oxytocin infected milk by pregnant woman increases risk of hemorrhage. It is also responsible for high spike in tuberculosis cases in humans. (e) Beef all over India has been found to be extremely toxic with large amount of this drug. (f) The direct infusion of this drug in vegetables, fruits and other consumables for humans is also widespread making such food items highly infected with Oxytocin.”

Astonishingly, the court does not cite a single scientific study or research paper to back its claims.

This is not insignificant because the central government in 2010 had commissioned the Indian Medical Research Council (ICMR) to address various health and safety issues related to Oxytocin. In one of the studies published in the Indian Journal of Medical Research, which is the official publication of the ICMR, a team of 5 scientists from the National Institute of Nutrition (a unit of ICMR) concluded that “These findings suggest that exogenous OT injections do not influence its content in milk. Further, OT present in milk is rapidly degraded during intestinal digestion, ruling out its intestinal absorption and associated adverse health consequences, if any.” In other words, there was no evidence that oxytocin administered on milch animals would have an adverse effect on the human body.

There is a second study, reportedly conducted by the National Dairy Research Institute (NDRI) in September, 2016 which reported that oxcytocin had no side-effects on the health of animals and milk because the hormone is a naturally occurring in milch animals and is similar to other hormones like insulin. The risk, as per the study, of continuously administering oxytocin is that the milch cattle develop an addiction and don’t respond to normal milk ejection stimuli. This second study has been cited by the incumbent Minister of Health J.P. Nadda in the Rajya Sabha on December 2, 2014 while responding to a question from Dr. Chandan Mitra asking the government whether it had studied the ill effects of Oxytocin on animals and human beings. The same study was cited once again by the incumbent Minister for Agriculture Radha Mohan Singh in response to a question in the Lok Sabha by Supriya Sule and Satav Rajeev on the effects of administering Oxytocin on animals. The amicus and by extension the High Court appear to have been entirely unaware of the above discussed studies because there is no mention of either study in the judgment.

The multiple regulatory deliberations on Oxytocin at the DCC

The two statutory bodies under the Drugs & Cosmetics Act are the Drugs Consultative Committee (DCC) and the Drugs Technical Advisory Board (DTAB). While the first is committee consisting of representatives of different state drug controllers with a mandate to ensure uniformity of regulations amongst the country, the second is an expert body consisting of regulators and independent experts with a mandate to provide technical advice to the Central Governmen i.e. the Ministry of Health & Family Welfare (MOHFW). Both bodies can only make recommendations to the MOHFW which then takes its own decision.

Maneka Gandhi

The issue of stricter regulation of Oxytocin was discussed at both the DCC and DTAB on multiple occasions, in response to petitions and questions in Parliament by Maneka Gandhi demanding action against the misuse of Oxytocin. The DCC discussed the issue on July 20, 2012 and November 12-13, 2013. The minutes of these meetings record mostly generic statements about the supposed misuse of Oxytocin and how it is pushed through clandestine operations – there is no mention of any statistics or verifiable source of information regarding the “widespread misuse”. The meeting in 2013, records that the issue was being taken up specifically because Maneka Gandhi had raised the issue of misuse of Oxytocin with the Secretary of Health. These two meetings of the DCC find mention in the High Court’s order. A third meeting not mentioned in the court’s order, took place on October 16, 2015 where Maneka Gandhi herself turned up before the DCC to share her views with the members. Going by the minutes, it does not appear that Maneka was even aiming for a ban of Oxytocin but better regulation of clandestine, illegal manufacture and sales.

The DTAB’s finding that Oxytocin & the central government’s orders

The DTAB first discussed this issue on November 25, 2013 because Maneka Gandhi had raised it in Parliament. Unlike the DCC meeting held just days earlier, the DTAB noted the fact that the Department of Animal Husbandry, Dairying and Fisheries, Ministry of Agriculture had not recommended the ban of the hormone for veterinary uses because it had therapeutic applications on animals. As a result, the DTAB declined to recommend a ban on the drug for veterinary uses. Instead it made generic recommendations to state drug controllers to curb misuse of the drug through increased surveillance and raids.

A few months after that meeting, on January 17, 2014 the central government issued an order under Section 26A of the Drugs & Cosmetic Act, 1940 ordering the formulations meant for veterinary uses to be sold to only veterinary hospitals while ordering bulk oxytocin manufacturers to supply the active pharmaceutical drug only to licensed manufacturers. The opening line of this particular order noted that the central government “is satisfied that the drug Oxytocin has a definite therapeutic use in certain medical conditions”.

Three months after that order was issued, on April 1, 2014 the DTAB met to discuss only Oxytocin; there was no other item on the agenda. The minutes of the meeting record, with some exasperation, that notwithstanding the order issued on January 17, 2014 tightening the distribution channels of Oxytocin, “Smt. Maneka Sanjay Gandhi, M.P. has however, again written to the Secretary, Ministry of Health and Family Welfare that the misuse of Oxytocin, is leading to a substantial loss of livestock in the country.” The minutes also record that the “Secretary, Health and Family Welfare, had therefore, desired that the matter should be expeditiously placed before the DTAB for its considerations.” Despite the pressure from Maneka Gandhi, the DTAB, to its credit, reiterated its position that the hormone has a definite role in the medical field both for humans and animals thereby ruling out any ban on the legitimate manufacture of the drug especially when sale of the hormone was possible only under prescription. Regarding the problem with manufacture and sale of the drug through illegal channels the DTAB concluded that the problem of misuse could not be countered by banning the drug. The committee instead prescribed a public awareness strategy combined with new rules on maintaining records of sales of Oxytocin.

Six months after the DTAB meeting, and after Maneka Gandhi became the Child Development Minister in the Modi cabinet, the then Drug Controller General of India (DCGI) G.N. Singh sent a circular to all state authorities, informing them that “Smt. Maneka Gandhi, Hon’ble Minister of Women & Child Development has taken up the matter with the Secretary, Ministry of Health & Family Welfare that the misuse of Oxytocin, is leading to a substantial loss of livestock in the country.” The circular then notes that an inter-ministerial committee was constituted by the MOHFW to study the problem and that the committee had recommended all state authorities to keep a strict eye on illegal use of Oxytocin and to investigate the sources of illegal supply. The circular also requests all state authorities to provide details of manufacturers of Oxytocin along with the statistical information on the seizures conducted, quantity seized, persons arrested, prosecutions filed during the previous three years. Finally, it appears, the central government was trying to collect information to figure out the scope of the allegations about Oxytocin misuse but the question is whether drug regulators were the appropriate authorities who could even collect such information.

State drug regulators can only regulate the quality and sale of the drug till the point of the sale (chemist). Thereafter, the manner in which a drug is misused by diary farmers on milch cattle falls within the jurisdiction of authorities under The Prevention of Cruelty to Animals Act, 1960. It is only police officers and other authorities under this legislation who can prosecute cases of misuse of Oxytocin on animals. Drug inspectors have no jurisdiction to prosecute cases of cruelty to animals. It follows that they will not have any credible information on the scale of misuse of Oxytocin. Going by the figures presented in Parliament on March 20, 2018 by Krishna Raj, the Minister of State of Agriculture and Farmers Welfare (also responsible for Animal Husbandry) in response to a question by MP George Baker, there were less than handful of prosecutions related to misuse of Oxytocin. His response in Parliament listed 8 cases in Chattisgarh related to seizure of Oxytocin injections, 1 case in Karnataka, 4 cases in Tamil Nadu and 7 cases in Uttar Pradesh. A different set of figures was put forth in Parliament on July 20, 2018 by the Minister of State for Health Ashwini Kumar Choubey who reported a total of 42 cases filed in the previous year by different state drug regulators and the central regulator. Most of these cases are likely for violation of the Drugs & Cosmetics Act rather than offences under the Prevention of Cruelty to Animals Act because as explained earlier, Drug Inspectors cannot prosecute cases of animal cruelty, they can only prosecute violations of the Drugs & Cosmetics Act. In the case of Oxytocin there are special rules requiring packaging of the hormone in a single blister pack which several manufacturers appear to be violating this rule attracting prosecutions from the regulators. In no event is this proof of misuse of the hormone on milch cattle.

In 2015, the DTAB took up the issue of Oxytocin twice, once at its 69th meeting on April 22 and a second time at its 70th meeting on August 18. The DTAB invited to these meetings, experts from the Indian Veterinary Research Institute (IVRI), ICAR – Ministry of Agriculture and the National Dairy Research Institute (NDRI). All the experts concurred that Oxytocin was required even for veterinary purposes and could not be banned. The problem identified by the experts was the unauthorised manufacture and sale of Oxytocin. The Joint Commissioner of FDA, Maharashtra stated in the 70th meeting that the Oxytocin manufactured by units licensed under the Drugs & Cosmetics Act was too expensive to be used by milkmen and that the problem was with raw material being smuggled across the border for crude manufacturing by unlicensed units. According to the Commissioner, it was this Oxytocin that was cheap enough to be used by dairy farmers. Both times, the DTAB agreed that the only response to the problem was increasing surveillance and educating diary farmers about the downsides of overusing Oxytocin.

The High Court and its judgment  

The High Court in its judgment dated March 15, 2016 takes note of only the DTAB meetings in 2013 and 2014, missing out the more detailed deliberations in 2015. The court then concludes, without citing any evidence whatsoever, “that inspite of various provisions of the Drugs and Cosmetics Act and other statutes in place, this Court cannot be oblivious to the fact that there is large scale manufacture and sale of drugs carried out in clandestine manner and that there is grave misuse of Oxytocin by farmers and dairy owners, which is the matter of great concern.”

The fact of the matter however is that not a single one of the meetings of the DCC or DTAB ever produced any particulars regarding the scope of the problem. It is thus baffling that the High Court concluded that the problem was rampant. However, convinced as it was about the misuse of Oxytocin, the court decided that it must issue directions for both the state government and the central government. One of these directions that was made to the State of Himachal Pradesh (and not the Union of India) was “to consider the feasibility of restricting the manufacture of Oxytocin only in public sector companies and also restricting and limiting the manufacture of Oxytocin, by companies to whom licenses have already been granted.” For almost two years, the central government did nothing about a feasibility report and rightly so since the direction was aimed at the state government and not the central government.

The pressing question now is what has changed between the 70th meeting of the DTAB held in August, 2015 and the order of the MOHFW on April 27, 2018 to force the MOHFW to restrict the manufacture of oxytocin to the extent that the domestic supply of this crucial hormone is restricted? The answer again, appears to be Maneka Gandhi.

Did Maneka propose restricting manufacture Oxytocin to only the public sector?

In June, 2017 several months before the government issued the order restricting manufacture of Oxytocin, the Hindu reported that the government was considering restricting the manufacture of the hormone by only public sector undertakings. The report attributes the idea for restricting the manufacture of the drug to Maneka Gandhi and even quotes her close associate Gauri Maulekhi backing the proposal. Maulekhi is perhaps better known for her role in forcing the government to introduce the highly controversial Prevention of Cruelty to Animals (Regulation of Livestock Market) Rules, 2017. Those rules which threatened to derail the entire cattle trade in the country, jeopardising the livelihoods of farmers, was the result of a PIL filed by Maulekhi before the Supreme Court in 2014.

The screws start tightening thanks to the Health Secretary

In March 30, 2017 just months before the report in the Hindu, the DCGI in a communication to state drug regulators, noted that the Secretary of Health had convened a meeting on March 14, 2017 to “take stock of situation relating to restrict and regulate manufacturing of Oxytocin and to permit its manufacturing in PSU in compliance to the judgment of the High Court of Himachal Pradesh”. It is not clear why the Secretary was under the impression that the High Court’s order was directed towards the central government when the recommendation to study the feasibility of restricting the manufacture to the PSU sector was directed at ‘respondent No.1’, the state government. Nevertheless, in September, 2017 the Ministry wrote to the DCGI instructing him to communicate to all state governments to take certain directions to comply with the terms of the High Court’s order. This included the constitution of special teams in each district to control the sale of Oxytocin, strictly enforcing licensing of manufacture of Oxytocin, publishing on the internet details of licences and monthly manufacturing of Oxytocin and finally steps to sensitise the pubic on misuse of oxytocin. Restricting manufacture to the public sector was not yet on the agenda.

The DTAB met once again on February 12, 2018 and Oxytocin was yet again on the agenda. The minutes of the meeting record a terse recommendation to prohibit the import of Oxytocin and restricting the supply of Oxytocin to only registered hospitals and clinics in both the private and public sector. Unlike the minutes of the earlier meetings that recorded the views of different members the minutes of this meeting only stated the final conclusion without any reasoning. More importantly though, the DTAB never made a recommendation to the Ministry to restrict manufacture to only the public sector.

The meeting with the manufacturers of Oxytocin & the restrictions that followed

Four days after the DTAB’s meeting, the new DCGI Eswara Reddy issued a notice summoning all the manufacturers of Oxytocin on February 22, 2018 to discuss the issue of illegal manufacture and use of Oxytocin since there were reports that the hormone was being misused in India on milch cattle. There was no mention in the notice of any plan to restrict manufacture of the drug to only the public sector.

After meeting the manufacturers, the DCGI issued a public notice on February 28, 2018 regarding the alleged misused of Oxytocin. The notice invited public comments on a proposal to restrict the manufacture of Oxytocin to only KAPL and also clearly mentioned the High Court’s judgment as the inspiration behind the move. The notice also made it clear that the private sector could still manufacture but only for export and not the Indian market. The notice was entirely silent on the earlier DTAB meetings that discussed the issue threadbare.

While the minutes of the meeting with the manufacturers are not publicly available, it is known is that the government clearly stepped up efforts on the Oxytocin issue in the months that followed. The push appears to have come from the Prime Minister’s Office as reported by the Wire which conducted a high-level meeting. The source cited in the Wire’s report was a circular issued on April 6, 2018 by the Anti-Smuggling Unit of the Central Board of Excise and Customs (CBEC) informing its various departments that subsequent to a meeting held at the Prime Minister’s Office (PMO) it was decided that all the bonafide requirements of Oxytocin should be met by indigenous production and all imports should be banned. All units were thus alerted to the possibility of smuggling and were instructed to keep vigilant.

Thereafter on April 9, 2018 Dr. Eswara Reddy chaired a meeting of the DCC consisting of all state drug regulators, where they were informed that amongst other measures DTAB at its meeting on February 12, 2018 had recommended restricting manufacture of Oxytocin only to public sector units. This was blatantly false because DTAB never made such a recommendation in its February meeting.

The orders under Section 10A & 26A

In April, the Ministry of Health issued two orders related to Oxytocin. The first was issued on April 24, 2018 under Section 10A of the Drugs and Cosmetics Act, 1940 prohibiting the import of Oxytocin into India, with immediate effect, on the grounds that the central government was “satisfied that the use of the drug Oxytocin and its formulation in any name or manner is likely to involve certain risk to human beings and animals and that it is necessary and expedient to prohibit the import of the said drugs in the public interest.” This was a grossly incorrect statement because government ministers in Parliament as well as the DTAB have time and again, reiterated that Oxytocin was of vital importance for both humans and animal. In fact, in its earlier Section 26A order issued in January, 2014 the MOHFW had categorically expressed its satisfaction that Oxytocin had a definite therapeutic use in certain medical conditions. What changed this conclusion?

The reason the MOHFW had to blatantly lie in this manner was because Section 10A of the Drugs & Cosmetics Act allows the government to prohibit import only if it is satisfied that the use of a drug is likely to involve any risk to human beings or if it lacks therapeutic value or lack therapeutic justification.

The second order was issued by the MOHFW on the April 27, 2018 under Section 26A of the same legislation and was to come into effect from July 1, 2018 (which date has been pushed to September 1, 2018). Unlike, the import ban order, the order under Section 26A was justified on the grounds that the High Court of HP had “observed” that “large scale clandestine manufacture and sale of Oxytocin was leading to its grave misuse, which is harmful to animals and humans”. This possibility of misuse is quite different from classifying the drug itself as a risk to animals and humans, as was the language used in the order under Section 10A.

Citing the High Court’s recommendation to study the feasibility of restricting Oxytocin to public sector units, as well as the DTAB recommendation to regulate the manufacture of the hormone, the order of the MOHFW imposes a number of conditions on the sale of Oxytocin, the most important of which was the decision to restrict manufacture for the domestic market to only the public sector, while allowing the private sector to continue manufacturing for exports. The order is entirely silent on how these supplies from the private sector would be barred from entering the domestic trade channels. In addition to restricting sales to the public sector, the order by the Ministry also disrupts the entire distribution market by mandating the sale of Oxytocin by the public sector directly to registered hospitals in the public or private sector or to specified government programs. The sale through chemists was completely prohibited. This means that regular trade channels are completely disrupted leading to severe market inefficiencies that will likely cause the price of the drug to spike once the ban is actually enforced.

The orders for a crackdown

Following this comical process, in the month of May, in preparation for the clampdown on Oxytocin, the DCGI issued an office memorandum informing his staff that the issue of misuse of Oxytocin had been discussed at the “highest levels of the government” before the orders were issued under Section 10A and Section 26A and that all officers of the Central Drug Standards Control Organisation (CDSCO) would have to launch special operations to prevent and detect illegal manufacturing, sale and distribution of Oxytocin with the cooperation of the police, if necessary. The circular ended with the direction that the matter was to be given the “top priority”. Sure enough, in the following months the CDSCO announced large seizures in Bihar, while the police in Hyderabad and Punjab also announced large seizures. While the seizure in Bihar was allegedly due to violation of packaging norms, the seizures in Hyderabad and Punjab appear to be blatantly illegal because neither police force has the power to seize those drugs from distributors unless they had proof that the drug was being illegally administered to milch cattle in a way that violated the Prevention of Cruelty to Animal Act, 1960.

Why did no one in the pharmaceutical industry challenge the order in April itself?

What is more intriguing about this entire episode is the fact that nobody in the pharmaceutical industry challenged the Ministry’s orders until July 31 when it was reported that Mylan challenged the legality of the order, although even that is not visible on the Delhi High Court’s website.

The chronology of the events documented in this bizarre episode raise some very basic questions which need some deliberations:

  1. The competency of the legal justice system to adjudicate issues that are deeply embedded in Science. Did the amicus accurately represent the facts and did the Bench understood the issues?
  2. The disproportionate influence that well-meaning activists have on policy making. Whether the actions of the Ministry led by the Minister Menaka Gandhi were driven by a specific agenda is anyone’s guess.
  3. The role of the regulator and the regulatory process once again in using scientific evidence to implement policy is once again highlighted in this episode. Political pressure notwithstanding, the role of the regulator is to speak for public health.

The larger question to ask at this stage, is who in the private sector is going to profit from the government’s extremely arbitrary actions and whether this regulatory action was a charade?

Prashant Reddy

Prashant Reddy

T. Prashant Reddy graduated from the National Law School of India University, Bangalore, with a B.A.LLB (Hons.) degree in 2008. He later graduated with a LLM degree (Law, Science & Technology) from the Stanford Law School in 2013. Prashant has worked with law firms in Delhi and in academia in India and Singapore. He is also co-author of the book Create, Copy, Disrupt: India's Intellectual Property Dilemmas (OUP). He has recently been appointed as an Assistant Professor at NALSAR, Hyderabad, starting September 1, 2017.

One comment.

  1. Freq. Anon.

    Dear Prashant,
    In depth past- as is always expected from you.
    Coming to industry angle, what is more surprising that the other big players in India have not even tried to protect their sale (unlike Mylan)! Wonder why none of the other players (if I recall, Pfizer India is a major player) did not challenge the actions?

    Reply

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