NCOVID-19: From detection to a cure, A regulatory overview

COVID-19 is the latest pandemic after cholera, the bubonic plague, smallpox, NIPAH, ZIKA and influenza-SARS, etc., to have accosted the world. A more aggressive variant of human coronaviruses that cause upper-respiratory tract illnesses, COVID-19 is a new disease, caused by a novel (or new) coronavirus that had hitherto not been seen in humans. The virus, having originated in China, has crossed borders and resulted in global lockdown. The race to find speedy detection and cure has begun at a feverish pace. Meanwhile, more than 300 Indians have already been diagnosed as COVID-19 positive. Six have succumbed to the disease.

Need to increase test centres & test kits

South Korea stepped up its testing efforts and has seen a low infection/ mortality count. Italy on the other hand delayed testing and is paying a price where infection/ mortality rates are highest, outside of Wuhan, China. As far as India is concerned, with current detection tests in short supply amidst no cure in sight, the government is facing its fair share of criticism, despite having taken numerous steps, for a somewhat slow response in so far as policies related to detection and testing are concerned. Infection rates in India are on the rise. Mortality is also seeing an increase.

 The World Health Organisation (“WHO”) has advised widespread testing to get an actual idea on the number of infected patients so that proper quarantine/ treatment measures can be taken, and authorities can plan accordingly. The Indian Council of Medical Research (“ICMR”), the apex body in India for formulation, coordination and promotion of biomedical research has, however, opined that the guidance was ‘premature’ for India, where community transmission has not yet been detected. Testing for COVID-19 in India has therefore been limited to only those who have travelled from affected countries/ come in contact with a confirmed case and shown symptoms after two weeks of quarantine or, patients with irregular pneumonia symptoms and symptomatic healthcare workers. ICMR has recently directed testing of asymptomatic direct and high-risk contacts of a confirmed case once between day 5 and day 14 of coming in contact with such person/ persons.

While testing was initially limited to identified government facilities, NABL-accredited[1] private laboratories have very recently been authorised to conduct testing. However, private labs have raised the issue of higher costs after the government requested them to provide these tests for free. While the issue is being deliberated and prices of tests seem to have been capped, there remains an acute shortage of testing kits. Currently most test kits are imported. The need of the hour is easy availability of test kits and additional testing centres. Accurate data would be the only way to ascertain if we have crossed the community transmission threshold or not. Speculation with regard to the extent of spread of the pandemic is detrimental to one and all.

What is the COVID-19 test?

The key identifier of any virus is the genetic information that is contained in its RNA – Ribo Nucleic Acid. According to the WHO, routine confirmation of COVID-19 cases is based on detection of unique sequences of virus RNA by Nucleic Acid Amplification Tests such as real-time reverse-transcription polymerase chain reaction (rRT-PCR), with confirmation by nucleic acid sequencing when necessary. These tests contain specific reagents and specialised machinery.

Limited supply of test kits

Test kits are in short supply, given the restrictions on plying of international flights and local lockdowns across nations. In the absence of local manufacturing, India is currently importing test kits and reagents. While the government has maintained that they have enough stockpiles of reagents and kits, it may not be enough.

Need for speedy approval

Newer and better test kits are being developed throughout the world at breakneck speed. Abbott, Roche, GenMark, Quest Diagnostics, etc., have developed effective testing kits. The US FDA has invoked emergency approval protocols for these tests and is granting approval on an out of turn expedited basis[2].

In India, according to news reports, many companies have requested the government to grant approval to manufacture these testing kits. But approval has been delayed for months now. At this stage, it is imperative to grant approvals expeditiously.

Regulatory framework & emergency approval provisions

Substances used for in vitro diagnosis are covered under ‘medical device’ definition under the Medical Devices Rules, 2017 (“MD Rules”)[3]. Covid-19 test kits fall under the said definition and also under the definition of the term ‘drug’ in terms of the Drugs and Cosmetics Act, 1940 (“D&C Act”).

In terms of the MD Rules[4], permission to import or manufacture in vitro diagnostic kits is granted by the licensing authority on the basis of an application, along with data on clinical performance, risk management, performance evaluation, clinical investigation, etc. However, data collection is time consuming. Interestingly, as per MD Rules[5], relaxation can be granted in cases of life threatening, serious diseases or diseases of special relevance to the Indian health scenario, national emergencies, extreme urgency, epidemic and where diagnostic devices are used for diagnosis of conditions, diseases for which there are no diagnostic medical devices available in the country. In such cases, clinical data requirements may be abbreviated, deferred or omitted, as may be deemed appropriate by the licensing authority.

The law provides for an expedited approval process, which is to be completed within a time frame of 90 days. The current emergency demands a shorter timeline. The regulator needs to take advantage of the emergency provisions as far as available within the existing statutes and waive off backup data requirements/ accept foreign approvals and data sets to the extent possible. Before testing kits approved elsewhere can be approved for large scale use, they need to be put through a performance evaluation test at a local level. The Drugs and Cosmetics Rules, 1945 provide for issuance of test licences for this purpose[6]. It has been reported that 18 companies have been granted test licences. Once a testing kit/ device can demonstrate safety and efficacy at a prima facie level, approvals must be granted, and regulatory oversight over such kits/ devices must be exercised by way of continuous post marketing surveillance.

Cure for COVID-19 – A Vaccine

With no effective vaccine in sight, biotech companies, universities have ramped up R&D efforts to find a cure before it’s too late. While some previously used drugs and treatment protocols have shown promise (retroviral drugs, flu treatment protocols), a hard-hitting cure is still elusive. For a virus vaccine, detailed trials are required to be conducted, not to mention the need to isolate the virus, study its genetic structure and find the best way to neutralise it. Adverse events associated with the use of the same would also need to be studied. Approval pathways as applicable for new drugs would need to be followed because vaccines fall under the category of ‘drug’ as per the D&C Act and any new vaccine, being a new drug would have comply with provisions of the New Drugs and Clinical Trial Rules, 2019 (“NDCT Rules”).

Approval pathway

The manufacture/ import of new drugs for the purpose of sale or distribution is regulated under Chapter X – Rule 76 of the NDCT Rules. Rule 75 of the NDCT Rules provides inter alia that in cases where a new drug contains an unapproved new molecule, the application for permission must be accompanied by data and other particulars, including result of local clinical trial as specified in the Second Schedule of the NDCT Rules (this includes information such as chemical and pharmaceutical information, animal pharmacology data, animal toxicology data, human clinical pharmacology data, etc.). The time taken to grant approval can stretch up to 90 working days. However, in terms of Rule 75(7), the information regarding local clinical trial may not be required to be submitted, along with the application in certain situations such as if the new drug is approved and marketed in countries identified by the Central Licencing Authority. Further, in terms of Rule 75(8), submission of requirements relating to animal toxicology, reproduction studies, teratogenic studies, perinatal studies, mutagenicity and carcinogenicity in application may be modified or relaxed in the event the new drug has been approved and marketed for more than 2 (two) years in other countries, if the Central Licencing Authority is satisfied that there is adequate published evidence regarding the safety of the drug[7].

Accelerated approval mechanism

The NDCT Rules[8] provide for an accelerated approval mechanism for drugs intended to be used in life threatening or serious disease conditions or rare diseases or for diseases of special relevance to the Indian scenario or unmet medical need in India, disaster or special defence. This fast track process provides for approval being based on data generated in clinical trials where surrogate endpoints are considered rather than using standard outcome measures such as survival or disease progression, which are reasonably likely to predict clinical benefit, or a clinical endpoint. Further, in situations where clinical safety evidence and efficacy have been established even if the drug has not completed the normal clinical trial phase, an application can be made to the licencing authority for expedited review process wherein the licencing authority will examine and satisfy certain conditions[9]. An application for expedited review can also be made for new drugs developed for disaster or defence use in extraordinary situations, such as war time, radiation exposure by accident or intention, sudden deployment of forces in areas with higher health risk, where specific preventive and treatment strategy is required, where new intervention in the form of new drug, route of delivery or formulation has been developed and where real life clinical trial may not be possible. Waiver of local trials may also be considered, and approval may be granted if foreign approval data sets are accepted. Approvals can be granted subject to detailed post approval surveillance reporting of adverse events.

Conclusion

 COVID-19 has presented India with a unique set of issues. Our large population is our biggest disadvantage. However, a lot depends on how the government handles these problems. While the law provides for emergency approval of tests, test centres and drugs in such national health emergency situations, delayed action may just prove to be an achilles heel in the fight against the pandemic. A pre-emptive and proactive approach over a reactive/ knee jerk approach is the need of the hour. Of course, citizens, too, have a role to play as the only way to beat this pandemic is to stand together and fight.


[1] https://www.mohfw.gov.in/pdf/LabTestingAdvisory.pdf

[2] https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#coronavirus2019

[3] Rule 3(zb) of the Medical Devices Rules, 2017 (“MD Rules”),

[4] Rule 64 of the MD Rules

[5] Rule 64 of the MD Rules

[6] Rule 33 of the D&C Rules. 33. Import of drugs for examination, test or analysis.  Small quantities of drugs the import of which is otherwise prohibited under section 10 of the Act may be imported for the purpose of examination, test or analysis subject to certain conditions.

[7] It may not be possible for companies to take benefit of Rule 75(8) as the 2 (two) year period prescribed under this provision may be too long in the fight against a highly contagious pathogen such as coronavirus

[8] Second Schedule of the NDCT Rules

[9] The conditions for expedited review process are:

  • it is for a drug that is intended to treat a serious or life threatening or rare disease or condition;
  • if approved, the drug would provide a significant advantage in terms of safety or efficacy;
  • there is substantial reduction of a treatment-limiting adverse reaction and enhancement of patient compliance that is expected to lead to an improvement in serious outcomes.
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Photo of Ashwin Sapra Ashwin Sapra

Partner in the General Corporate Practice at the Delhi Office of Cyril Amarchand Mangaldas. With a specialist focus on intellectual property, pharmaceuticals / medical devices regulatory and compliance affairs, Ashwin has an extensive domestic and international experience of 19 years providing advice on…

Partner in the General Corporate Practice at the Delhi Office of Cyril Amarchand Mangaldas. With a specialist focus on intellectual property, pharmaceuticals / medical devices regulatory and compliance affairs, Ashwin has an extensive domestic and international experience of 19 years providing advice on matters relating to intellectual property, drug and medical device regulatory and compliance affairs, transactional affairs, anti corruption and anti kick back laws, litigation and dispute resolution. He can be reached at ashwin.sapra@cyrilshroff.com

Photo of Biplab Lenin Biplab Lenin

Principal Associate in the Pharmaceutical, Healthcare & Life Sciences Practice at the Delhi office of Cyril Amarchand Mangaldas. Biplab specializes in regulatory, transactions, advisory and disputes pertaining to drug, medical devices, biotechnology, intellectual property including patents, plant variety and biodiversity. He can be…

Principal Associate in the Pharmaceutical, Healthcare & Life Sciences Practice at the Delhi office of Cyril Amarchand Mangaldas. Biplab specializes in regulatory, transactions, advisory and disputes pertaining to drug, medical devices, biotechnology, intellectual property including patents, plant variety and biodiversity. He can be reached at biplab.lenin@cyrilshroff.com

Photo of Kartik Jain Kartik Jain

Associate in the Pharmaceutical, Life-sciences and Healthcare practice at the Delhi office of Cyril Amarchand Mangaldas. Kartik graduated from National Law University, Delhi in 2018 and specializes in regulatory compliance, advisory work and litigation pertaining to the pharmaceutical and health-care industry. He also…

Associate in the Pharmaceutical, Life-sciences and Healthcare practice at the Delhi office of Cyril Amarchand Mangaldas. Kartik graduated from National Law University, Delhi in 2018 and specializes in regulatory compliance, advisory work and litigation pertaining to the pharmaceutical and health-care industry. He also has experience in labour and employment matters, having worked in the Employment laws practice at the firm’s Delhi office. He can be reached at kartik.jain@cyrilshroff.com.

Photo of Jashaswi Ghosh Jashaswi Ghosh

Associate in the Pharmaceutical, Healthcare & Life Sciences Practice at the Delhi office of Cyril Amarchand Mangaldas. Jashaswi has graduated from Gujarat National Law University, in 2018 and specializes in regulatory compliance, advisory work and litigation pertaining to the pharmaceutical and health-care industry.

Associate in the Pharmaceutical, Healthcare & Life Sciences Practice at the Delhi office of Cyril Amarchand Mangaldas. Jashaswi has graduated from Gujarat National Law University, in 2018 and specializes in regulatory compliance, advisory work and litigation pertaining to the pharmaceutical and health-care industry. He also has experience corporate laws and litigation having worked in the general corporate and disputes teams in the firm’s Mumbai Office. He can be reached at jashaswi.ghosh@cyrilshroff.com