Conservationists Seek Ban on Three Vulture-Toxic Veterinary Drugs : Steps for Banning Veterinary Drugs in India
Sixteen years after India banned veterinary use of diclofenac, found to be toxic for vultures, scientists and conservationists are calling for a ban on veterinary painkiller aceclofenac.
In fact, it’s one of three veterinary drugs that need to be banned for being “vulture-toxic”, say conservationists, who have approached the Ministry of Environment, Forest and Climate Change to raise the issue with the Drugs Controller General of India (DCGI). The other two drugs are nimesulide and ketoprofen. A public interest litigation on the issue is also at the Delhi High Court.
Asian vulture population
India is home to about 80 per cent of the Asian vulture population, and four of the nine species are critically endangered, says Abhishek Ghoshal, Conservation Scientist with BNHS (Bombay Natural History Society).
“Aceclofenac is a pro-drug and gets converted in the body of large cattle to diclofenac (the banned drug),” Ghoshal told businessline, of the danger the drug poses to the vulture that feeds on the carcass. The other two drugs too are vulture-toxic, he said, concerned at their impact on certain species already on the brink. In March 2022, dossiers on these drugs were presented to the MoEFCC, along with information on alternative drugs (meloxicam and tolfenamic acid) that are vulture-safe, so this could be taken up with the DCGI, he said. In May, a lawyer approached the Delhi High Court on the issue.
State authorities have the authority to act, based on the evidence provided, even as the Centre reviews the issue, says Ghoshal, citing Tamil Nadu as a good example where pro-active action had been taken. Assam too has seen affirmative action, with the alternative drug meloxicam being available at pharmacies to cattle owners, he said. The diclofenac ban in veterinary use needs to be better enforced, he said, and cattle owners too need to be educated on the efficacy of the alternatives.
A recently published study by the Indian Veterinary Research Institute (IVRI) and collaborators echoed similar observations. It found that aceclofenac metabolised into diclofenac in water buffaloes, as it did in cows, threatening the already critically endangered Gyps vultures in South Asia. “We recommend an immediate ban on the veterinary use of aceclofenac across vulture range countries,” the paper said.
AM Pawde, a co-author of the paper and Principal Scientist and Incharge IVRI, said, “Government is spending crores in vulture conservation programmes, but this is getting affected,” by the unregulated use of drugs like aceclofenac in large animals.
Chris Bowden, programme manager-SAVE (Saving Asia’s Vulture’s from Extinction) also calls for aceclofenac’s ban, as it is effectively diclofenac, he says, and a loophole is being exploited “by manufacturers and irresponsible vets and practioners at the cost of vultures…”
Several mid-size drugmakers make aceclofenac and combinations, say the conservationists, concerned about the manufacturing practices and regulatory checks on these companies and products, and the end-result on vultures. Given recent incidents of toxic contaminants found in cough syrups, they say, the situation with human medicine would only be mirrored, if not worse with veterinary drugs.
The Central Drugs Standard Control Organisation (CDSCO) has passed the buck on banning three drugs that are used to treat livestock but are toxic for vultures – a protected species – to the Department of Animal Husbandry and Diarying, expressing its inability to take the decision without the latter’s concurrence.
The CDSCO’s statement runs contrary to the strategy laid out in the ‘Action Plan for Vulture Conservation (2020-25)’, which says that India’s drug regulator has to institute a system where any drug that is demonstrably found to be toxic to vultures must be automatically removed from the market.
The drug regulator made the submission in an affidavit filed in the Delhi high court in an ongoing case on vulture protection. The case was heard on Tuesday, December 13, 2022, when the court asked the regulator to file a status report on the steps it has taken to protect India’s vultures, according to the petitioner in the case Gaurav Bansal, a Supreme Court lawyer.
The CDSCO said that it cannot ban three drugs – aceclofenac, nimesulide and ketoprofen – for veterinary use without the concurrence of the animal husbandry department, which falls under the Union Ministry of Fisheries, Animal Husbandry and Dairying.
These three are among many drugs classified as toxic non-steroidal anti-inflammatory drugs (NSAIDs), which are used to treat pain, fever and other inflammatory conditions in livestock like cattle. When vultures consume the carcasses of animals treated with these medicines, they also consume the toxic effects of the drugs, leading to kidney failure.
Three species of vultures – including those that have witnessed drastic population declines – are listed in Schedule I of the Wildlife Protection Act, 1972, which affords them the highest level of protection in Indian law.
The decline in vulture populations was highlighted in the mid-80s, and in 2004 the cause of the crash was established as diclofenac, a veterinary NSAID. Bansal’s affidavit, quoting a statement from the MoEFCC, said the vulture population has declined from 40 million to 19,000 in the last three decades.
Though the Drug Controller General of India (DCGI) – the CDSCO’s head – banned the veterinary use of diclofenac in 2006, its illegal use continues. In 2015, the DCGI also restricted the vial size of the human formulation of diclofenac to prevent its misuse. Aceclofenac, one of the three drugs that the petition in the Delhi high court seeks to be banned, gets metabolised into diclofenac.
The Wire Science had earlier reported that the CDSCO was dragging its feet in banning aceclofenac, nimesulide and ketoprofen for veterinary use despite the Wildlife Institute of India (WII) and the Indian Veterinary Research Institute (IVRI) – both set up by the Union government – writing to it on several occasions to prohibit their use.
Interestingly, the animal husbandry department, to which the CDSCO has deferred the decision now, says it has no information on whether “it has any policy on protection and conservation of vultures”.
Bansal had filed a Right to Information (RTI) application with the animal husbandry department on July 8, 2022, asking if it had a policy for vulture conservation and if there was any official file to that effect. The department transferred his application to the Animal Welfare Board of India (AWBI), which works under its aegis. AWBI replied, “The information sought is not available with the Board.”
Now, the CDSCO has told the Delhi high court that it had written to the animal husbandry department at least four times in the past seeking its opinion on banning the drugs. The drug regulator said:
“It is humbly submitted that for prohibiting/banning of Veterinary Drugs by Ministry of Health and Family Welfare [under which CDSCO functions], the Expert opinion from the Department of Animal Husbandry and Dairying is required. Decision regarding approval of new drugs for veterinary use is done in accordance with review/comments by Department of Animal Husbandry and Dairying.”
The regulator also said that as per the Drugs and Cosmetics Act 1940, its approval for new drugs for animal use has to rely on the assessment of clinical data done in “coordination” with the animal husbandry department.
The CDSCO furnished copies of four letters written in 2019, 2020, 2021 and 2022 to the court.
In the letter written on July 8, 2019, the CDSCO told the department that it had received a letter from Haryana’s drug controller advocating for the prohibition of aceclofenac for veterinary use. On December 22, 2020, it sent a reminder to the Department, adding that Goa’s drug controller had also made a similar pitch not just for aceclofenac but also ketoprofen. In 2021 and 2022 also, it sent similar letters to the department.
In the last letter, written on June 23, 2022, the CDSCO wrote:
“In view of above [reminder of earlier letters], you are once again requested to kindly examine the matter and convey your expert opinion at the earliest, so as to take further necessary action for banning of Ketoprofen & Aceclofenac for treatment of livestock animals to conserve vultures.”
The CDSCO told the Delhi high court that it did not get a response to any of these letters. Therefore, it could not take any action on the prohibition or ban of the three drugs for veterinary use and is waiting to hear from the animal husbandry department.
What does the conservation plan say?
While the CDSCO is relying on the animal husbandry department to ban these three drugs for use in animals, the ‘Action Plan for Vulture Conservation (2020-25)’, prepared by the Union Ministry of Environment, Forest and Climate Change (MoEFCC), envisages no role for the latter in drug regulation.
Though the plan is to be implemented by MoEFCC, there is “very little” that the ministry can do on its own “as the cause of crash in vulture populations is the veterinary use of NSAIDs”.
As far as drug regulation is concerned, the plan says:
“[While] the licensing and the distribution of the drugs is the responsibility of the Drug Controller General of India [CDSCO’s head] of the MoH&FW, [the] dispensing and administration is the responsibility of the Animal Husbandry Commissioner of the Ministry of Animal Husbandry, Dairying and Fisheries.”
Indeed, the plan gives four specific responsibilities to the department of animal husbandry but all of them are related to implementing the decisions that are taken by the National Committee for Implementation of the Action Plan, and ensuring that there is no illegal use in treating animals.
The DCGI – the head of the CDSCO – is also a member of the national committee formed for the implementation of the vulture conservation plan.
The plan also says:
“If a drug is found to be toxic by a scientific study and it is published in [a] high impact factor international journal, it should be automatically removed from the veterinary market once the paper is reviewed by the technical committee of DCGI.”
Now, according to an affidavit submitted by the non-profit organisation Bombay Natural History Society in the ongoing Delhi high court case, studies have been published since 2010 showing the toxic effects of aceclofenac, nimesulide and ketoprofen. The details of the affidavit were earlier reported by The Wire Science.
The plan, which was published in 2020, also explicitly mentions that the DCGI must institute a system to ensure that drugs that are toxic to vultures like “aceclofenac and ketoprofen are banned for veterinary use.”
The WII, which functions under the MoEFCC, is of the view that banning these three drugs will not impact the treatment regimen for cattle and livestock, listing alternative medicines in a letter addressed to the ministry on July 7, 2022.
The IVRI, which reports to the Indian Council of Agriculture Research, also recommended the same alternatives in its July 21, 2022 letter to the environment ministry, as reported earlier.Now, the CDSCO has to file its reply within four weeks.
Steps for banning veterinary drugs in India:
SAVE accords a very high priority to achieving bans on veterinary use of NSAIDs that have been proven to be toxic to vultures (see India policy summary). The bans on veterinary use of diclofenac in 2006 in India, Nepal and Pakistan and in 2010 in Bangladesh were important steps and were enacted by the governments with commendable speed. However, we know that further such steps are urgently needed to ban veterinary use of other NSAIDs toxic to vultures. Achieving such bans in the near future is vital. Some progress with this is being made in India, but Bangladesh has taken an important lead with its national ketoprofen ban.
Here we list the steps for achieving such a ban with the intention of making information on how to do it readily available. We welcome feedback on this document in case our list of steps is incorrect, incomplete or works differently in other SAVE member states.
Process of Banning Veterinary Drugs in India
Step 1: An organisation (or individual) writes to the Drug Controller General of India (DCGI) formally requesting a ban of a specific drug, sent together with copies of relevant publications and other documents directly relevant to this request (these become the file or dossier).
- Although this request can theoretically come from anywhere, it is likely to be taken more seriously if submitted by a reputable organisation or, even better, by a government body. The file should contain robust, quantitative and clearly presented supporting information. Ideally, peer-reviewed scientific papers should be included. Given that the effects of NSAIDs have been shown to be similar for all Gyps vulture species tested in Eurasia and Africa, properly conducted studies based upon research done in any country should be
Step 2: At the discretion of DCGI, he/she agrees to review the request and passes the request and file to the ‘Technical Drugs Regulation Review Committee’ (TDRRC) which consists of 4-5 highly qualified and appointed experts. The TDRRC meets 4 times/year and reviews the validity of such requests and will put such requests on their meeting agenda assuming the file is considered adequately prepared.
- DCGI meanwhile consults the Animal Husbandry Commissioner (AHC) and includes feedback from the AHC within the file for review.
Step 3: The Technical Committee (TDRRC) may require repeated discussion at successive meetings and gathering of further information before reaching a conclusion. When it has done so, a recommendation for approval or rejection of the requested ban is returned, together with the file of supporting data, to the DCGI.
Step 4: If the recommendation is for the approval of a ban, then the DCGI normally endorses this and passes the file to the Secretary of Ministry of Health.
Step 5: Secretary of Health normally signs approval and passes the file for the final legal approval of the Law Ministry for passage into legislation.
Step 6: The Law Ministry publishes the signed decision into law.
Step 7: Final Gazettement of the decision may take a further year or two, but legally the ban is binding before this stage. This step may not be necessary if the ban is considered to already be part of earlier legislation
The ban on veterinary diclofenac of 2006 passed through these steps and was gazetted in 2008. The restriction of vial size of human formulations of diclofenac was passed in 2015, and was immediately gazetted due to the clear link with the 2008 ban. In both cases, the Bombay Natural History Society (BNHS), filed the original case with help and support from numerous parties at various stages. Note the contents of the file (dossier) are an important resource for upholding any subsequent challenges to the ban, and such challenges have been handled mainly by the DGCI’s office, but have also resulted in court cases.
Subsequent requests for veterinary drug bans in India:
2008: Ketoprofen was demonstrated to be toxic to vultures and a peer-reviewed scientific paper giving the experimental evidence for this was published was published online in 2009 (print publication: Naidoo et al (2009) Biology Letters (2010) 6, 339–341. https://doi.org/10.1098/rsbl.2009.0818). Additional experimental evidence of toxic effects on vultures was published in a further peer-reviewed scientific paper in 2010 (Naidoo et al. Archives of Toxicology (2010) 84:761–766. DOI 10.1007/s00204-010-0521-0). A peer-reviewed scientific paper reporting the prevalence and concentrations of nine NSAIDs in the carcasses of cattle available to vultures in India in 2006 was published in 2009 (Taggart et al. Environmental Science & Technology (2009), 43: 4561–4566.). This study showed that ketoprofen was a contaminant of cattle carcasses in India and that tissues of some cattle contained enough of the drug to cause the death of vultures. The supporting file was submitted by BNHS in 2009 but was not progressed by the DCGI. Hence, this application is still at Step 1 after 12 years.
2019: Aceclofenac was confirmed to be a pro-drug of diclofenac, and to pose a very significant threat to vultures as it is effectively the same as diclofenac. A peer-reviewed scientific paper giving the experimental evidence that aceclofenac is rapidly converted to toxic diclofenac in cattle dosed with the drug was published in 2016 (Galligan et al. (2016) Conservation Biology, 30: 1122–1127. DOI: 10.1111/cobi.12711). A study showing the same result in domestic water buffaloes was conducted by the Indian Veterinary Research Institute in 2020. BNHS submitted a request to ban veterinary use of aceclofenac with a supporting file in March 2019. It remains under review of the TDRRC. Hence, this application is at Step 2 after two years.
2021: Nimesulide has been confirmed to be a toxic drug to vultures, with peer-reviewed publications confirming wild birds found dead in India with gout symptoms and nimesulide in the tissues (Nambirajan et al. 2021) , and safety trials demonstrating toxicity (Galligan et al. in press). There has been no submission (Step 1) so far so this is currently at Step 0.
2021: Flunixin has also been found both in dead wild vultures and treated captive vultures showing gout symptoms in Europe (Zorrilla et al. 2014, Eleni et al. 2019). But no clinical trials have been carried out so far, and is still at Step 0.
2021: Carprofen has demonstrated toxicity to vultures, although it appears to remain at high concentrations only close to the injection site of cattle tissues (Fouri et al. 2015).
2021: Paracetamol, ibuprofen, piroxicam and all other veterinary NSAIDs remain untested on vultures and therefore have unknown toxicity.
Note: For the current status and references relating to each toxic NSAID, refer to the Policy Summary for India which can be downloaded from the SAVE website here:
Reference-https://science.thewire.in/environment/cdsco-animal-husbandry-department-drugs-toxic-vultures/
https://www.thehindubusinessline.com/news/science/conservationists-seek-ban-on-three-vulture-toxic-veterinary-drugs/article66255393.ece
CDSCO Passes Buck to Animal Husbandry Dept on Banning Drugs Toxic to Vultures
