DCGI approves anti-COVID drug- BY DRDO & Clinical Trials
GS-Paper-3: S&T - Innovation – UPSC PRELIMS – Mains Application
Context: An anti-COVID-19 therapeutic application of the drug 2-deoxy-D-glucose (2-DG) has been developed by Institute of Nuclear Medicine and Allied Sciences (INMAS), a lab of Defence Research and Development Organisation (DRDO), in collaboration with Dr Reddy’s Laboratories (DRL), Hyderabad.
An anti-COVID-19 therapeutic application of the drug 2-deoxy-D-glucose (2-DG) has been developed by Institute of Nuclear Medicine and Allied Sciences (INMAS), a lab of Defence Research and Development Organisation (DRDO), in collaboration with Dr Reddy’s Laboratories (DRL), Hyderabad.
Clinical trial results have shown that this molecule helps in faster recovery of hospitalised patients and reduces supplemental oxygen dependence.
Higher proportion of patients treated with 2-DG showed RT-PCR negative conversion in COVID patients. The drug will be of immense benefit to the people suffering from COVID-19.
- Pursuing Prime Minister call for preparedness against the pandemic, DRDO took the initiative of developing anti-COVID therapeutic application of 2-DG.
- In April 2020, during the first wave of the pandemic, INMAS-DRDO scientists conducted laboratory experiments with the help of Centre for Cellular and Molecular Biology (CCMB), Hyderabad and found that this molecule works effectively against SARS-CoV-2 virus and inhibits the viral growth. Based on these results, Drugs Controller General of India’s (DCGI) Central Drugs Standard Control Organization (CDSCO) permitted Phase-II clinical trial of 2-DG in COVID-19 patients in May 2020.
The Drug Controller General of India (DCGI) is the head of the Central Drugs Standard Control Organisation (CDSCO) in India.
- CDSCO is the central drug authority in India.
- CDSCO is a national level regulatory body under the Ministry of Health and Family Welfare.
- The body is responsible for approving licenses for certain categories of drugs.
- It is headquartered in New Delhi.
- There are six functioning central drug testing laboratories under CDSCO.
- The DCGI also establishes standards for the manufacturing, sales, import, and distribution of drugs in India.
- The DCGI also regulates medical and pharmaceutical devices.
- In case of any dispute with respect to the quality of the drug, the DCGI is the appellate authority.
- The DCGI prepares and maintains the national reference standard for drugs.
- He ensures that there is uniformity in the implementation of the Drugs and Cosmetics Act.
- He is responsible for the training of Drug Analysts deputed by State Drug Control Laboratories and other Institutions.
- He is also in charge of the analysis of cosmetics received from the CDSCO as survey samples.
- The DCGI is also the central licensing authority for medical devices which fall under the Medical Device Rules 2017.
The CDSCO is responsible for the following:
- Drug approval under the Drugs and Cosmetics Act.
- Conducting clinical trials. Setting standards for drugs.
- Quality control over drugs imported into the country.
- Coordinating activities of the state drug control organisations.
- Registration of foreign manufacturers of drugs and medical devices whose products are to be imported into the country.
- Grant of licences to import drugs by Government hospitals or Medical Institutions for the use of their patients.
- Recommend banning of drugs considered harmful or sub-therapeutic under section 26A drugs and Cosmetics Act.
- The DRDO, along with its industry partner DRL, Hyderabad, started the clinical trials to test the safety and efficacy of the drug in COVID-19 patients.
- In Phase-II trials (including dose ranging) conducted during May to October 2020, the drug was found to be safe in COVID-19 patients and showed significant improvement in their recovery.
- Phase II was conducted in six hospitals and Phase IIb (dose ranging) clinical trial was conducted at 11 hospitals all over the country. Phase-II trial was conducted on 110 patients.
No clinical trials-for new drugs
- Union Ministry of Health and Family Welfare has allowed waivers on conducting trials for new drugs in India in case the drug is approved and marketed in countries specified by — the Central Drugs Standard Control Organisation (CDSCO).
- New drugs approved for use in select developed markets will be automatically allowed in India provided global trials included Indian patients.
- This waiver would also extend to drugs that receive these marketing approvals even while a trial is underway in India.
- Data generated(clinical trial) outside the country will be acceptable.
- Providing post-trial access of the drugs to the patients that require it have been defined for the first time.
- It removed a clause in the clinical trials that mandated the sponsor (the entity initiating the trial) to pay 60% of compensation upfront in case of death or permanent disability of a patient.
- Now companies will pay the total amount once it is proven that the injury occurred because of the trial.
- Compensations in cases of death and permanent disability, or “other” injuries to a trial participant will be decided by Drug Controller General of India(DCGI).
- It removed regulations on tests conducted on animals in case of drugs approved and marketed for more than two years in well-regulated overseas drug markets.
Significance of New Rules
- It will end the unnecessary repetition of trials and speed up the availability of new drugs in the country.
- It will lower the cost of drugs.
- It will improve the ease of doing business for drug makers.
Criticism of new regulations
- India is a country of vast ethnic diversity and most of the trials are done in the West. There is need of bridging trials for ethnically diverse populations to check drug suitability population.
- Waiver should be only for drugs required urgently for national emergency.
- Proving injury due to the trial is problematic and it is prone to manipulation.
- In efficacy trends, the patients treated with 2-DG showed faster symptomatic cure than Standard of Care (SoC) on various endpoints. A significantly favourable trend (2.5 days difference) was seen in terms of the median time to achieving normalisation of specific vital signs parameters when compared to SoC.
- Based on successful results, DCGI further permitted the Phase-III clinical trials in November 2020. The Phase-III clinical trial was conducted on 220 patients between December 2020 to March 2021 at 27 COVID hospitals in Delhi, Uttar Pradesh, West Bengal, Gujarat, Rajasthan, Maharashtra, Andhra Pradesh, Telangana, Karnataka and Tamil Nadu.
- The detailed data of phase-III clinical trial was presented to DCGI. In 2-DG arm, significantly higher proportion of patients improved symptomatically and became free from supplemental oxygen dependence (42% vs 31%) by Day-3 in comparison to SoC, indicating an early relief from Oxygen therapy/dependence.
The similar trend was observed in patients aged more than 65 years. On May 01, 2021, DCGI granted permission for Emergency Use of this drug as adjunct therapy in moderate to severe COVID-19 patients. Being a generic molecule and analogue of glucose, it can be easily produced and made available in plenty in the country.
The drug comes in powder form in sachet, which is taken orally by dissolving it in water. It accumulates in the virus infected cells and prevents virus growth by stopping viral synthesis and energy production. Its selective accumulation in virally infected cells makes this drug unique. In the ongoing second COVID-19 wave, a large number of patients are facing severe oxygen dependency and need hospitalisation. The drug is expected to save precious lives due to the mechanism of operation of the drug in infected cells. This also reduces the hospital stay of COVID-19 patients.
Phases of CLINICAL TRIALS
Clinical trial is a long and careful research process which is conducted in a step-by-step exercise usually comprising of the following phases:
- Phase-0/Pre-clinical testing: The clinical trial often starts in a laboratory with the scientists finalising their ideas. If they are convinced, they start with animal testing. After all the things seems to be working well, the research on humans is needed.
- Phase-1: It is the first study conducted on people in the clinical trial process. Here, the healthy participants (a small number) are given a fixed dosage and are watched closely. The aim of the study is to find the safest dose and the best treatment that can be given. It identifies side effects and studies how the dose works with other medicines or food.
- Phase-2: In this phase, the study builds upon the results of Phase-1. It further tests the safety of drug along with its effectiveness. Here, more participants are involved. Now either all the participants are given the same experimental dose or sometimes the participants are divided into groups and given different treatment doses to compare. This phase can last for several years.
- Phase-3: In this phase, the participant size is in hundreds to thousands. Here, tests are conducted to find if the treatment is better than the standard treatment available. It then compares side effects, survival rate and quality of life between the two. This phase runs over a long period of time.
- Phase-4/ Post-marketing trials: In this phase, the participant size is in thousands. The studies are conducted only after the treatment has been registered with the drug regulator. This is usually done by pharmaceutical companies that manufacture the product. The study helps to identify how well the treatment is working when used widely. The long-term benefits and risks are also monitored. It further looks for the other uses of the drug or treatment other than intended ones.