CME INDIA Presentation by Admin.
2021 has been perceived as a year of Hope with emergency approval of 2 vaccines for COVID-19. First indigenously developed Indian COVID vaccine – COVAXIN has not completed the phase 3 trial. But considering all pros and cons, DCGI has given approval for its very specific use at present. CME INDIA discusses this most exciting issue of mankind at present…
Vaccination Is the Only Acceptable Path to Herd Immunity
Angela L. Rasmussen:
- Population-level herd immunity is critical for long-term control of SARS-CoV-2.
- However, proposals to reach the herd immunity threshold through naturally acquired infection, rather than vaccination, have complicated public health efforts and popularized policies that will lead to widespread transmission and mortality.
- Vaccination is the only viable path to herd immunity.
It will be Historic in Indian Medicine
|Product name; Dose/Route||Type||Manufacturer||Collaborator||Approval DCGI|
|COVISHIELD; Two doses, 0-28 IM||Viral Vector Non-replicating||Serum Institute of India, Pune||Astra Zeneca||01/01/2021|
|COVAXIN; Two doses, 0-28 IM||Inactivated virus||Bharat Biotech Ltd. Hyderabad||ICMR||03/01/2021|
Controversies: Take with a pinch of salt
Facts to Know About Oxford-AstraZeneca-SII’s Covishield
- On Friday, January 1, 2021, the Subject Expert Committee (SEC) on COVID-19 of the Central Drugs Standard Control Organisation (CDSCO) reviewed the application
- It recommended the grant of emergency use authorisation (EUA) for SII’s Covishield.
- Covishield will be the first vaccine to be approved for public
- The UK government has already issued an emergency use authorisation for the Oxford-AstraZeneca COVID-19 vaccine on December 30.
- The Oxford-AstraZeneca COVID-19 vaccine is proven to be safe with no major side-effects reported throughout the human trials. It is shown to generate strong antibody and T-cells response for long-term immunity against the novel coronavirus SARS-CoV-2.
- Among limited number of participants, who received a lower first dose followed by a full second dose, the efficacy went up to 90%. The overall efficacy, combining different dosage groups, was shown to be 70%.
- The easy storage and transportation benefits of Covishield is win win situation in India. The Oxford-AstraZeneca vaccine can be stored at regular fridge temperatures.
- The vaccine uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) and contains the genetic material of the SARS-CoV-2 virus spike protein.
- After vaccination, the surface spike protein is produced in the human body without any impact of the actual COVID-19 disease, enabling the immune system to attack the SARS-CoV-2 virus if it infects the body in future.
- It is worth to note that the SII has already manufactured 5 crore doses of the vaccine and is progressively building its stock under the at-risk manufacturing and stockpiling licence from the DCGI, and aims to produce around 30 crore doses by July 2021.
- The SII has an agreement with AstraZeneca to produce 100 crore doses, mainly for supply to developing countries.
- Efficacy of Covishield
- Oxford’s COVID-19 vaccine candidate has a better immune response when a two full-dose regimen is used rather than a full-dose followed by a half-dose booster as per the university.
- The vaccine candidate, which has been licensed to AstraZeneca, previously published interim late-stage trial results showing higher efficacy when a half dose was followed by a full dose, compared to a two full-dose regimen, though more work needs to be done to affirm the result.
- Overall efficacy of 70% is lower than the 90-95% being reported for mRNA vaccines from Pfizer-BioNtech and Moderna; and from the Russian Sputnik adenoviral vector vaccine.
- Adverse effects Covishield
- No serious adverse events or deaths occurred that were treatment associated in ChAdOx1 nCoV-19 recipients.
- But there were 175 serious adverse events (84 in the ChAdOx1 nCoV-19 group and 91 in the control group), three of which were possibly related to the intervention: transverse myelitis occurring 14 days after a ChAdOx1 nCoV-19 booster vaccination, haemolytic anaemia in a control recipient, and fever higher than 40°C in a participant still masked to group allocation.
- The transverse myelitis cases resulted in temporarily pausing the trial and all participants have recovered or are recovering
- “Disparity between immunogenicity and efficacy findings could imply that clear-cut immunological correlates of clinical protection might not exist for COVID-19 vaccines, meaning efficacy cannot be extrapolated to other unevaluated ages or populations”-Editorial in Lancet
- TAKE HOME – Covishied vaccine:
- Good promise for affordable compared with the high cost of the two mRNA vaccines that have reported more than 90% efficacy.
- ChAdOx1 nCoV-19 has an acceptable safety profile.
- It has been found to be efficacious against symptomatic COVID-19.
- The ChAdOx1 nCoV-19 vaccine can also use routine refrigerated cold chain, which is important since the ultra-low temperature freezers required to store mRNA vaccines could be unaffordable and impractical in many countries
The saga of Indian Endeavour
- Covaxin is India’s first indigenous vaccine against COVID-19.
- It has been developed by Bharat Biotech in collaboration with the Indian Council of Medical Research and National Institute of Virology.
- Congratulations India-PM Modi tweets, when DCGI gives final approval of Bharat Biotech vaccine
- Covaxin is an inactivated vaccine. This destroys the pathogen’s ability to replicate, but keeps it intact so that the immune system can still recognise it and produce an immune response.
- There are many inactivated vaccines against Hepatitis A, Influenza, Polio, Rabies, which offer “excellent protection”.
- The Serum Institute of India submitted data of phase 1 clinical trial conducted over 23,745 overseas participants showing an overall result of 70.42 per cent efficacy.
- In phase two and three, which were conducted in India, 1,600 participants took part and the results were comparable to that of the first phase of trial. Its third trial is going on and a total of 22,500 already participants took part in it.
- The vaccine has been found effective and safe-DCGI
- Covishield will cost around Rs 400-Serum Institute. Bharat Biotech’s vaccine is likely to cost less than Rs 100.
- VG Somani, Drug Controller General of India (DCGI) Says:
- We’ll never approve anything if there’s slightest of safety concern. Vaccines are 110 % safe. Some side effects like mild fever, pain & allergy are common for every vaccine. It (that people may get impotent) is absolute rubbish:
- The overall efficacy of the Oxford-AstraZeneca COVID-19 vaccine was 70.42%, while Bharat Biotech’s Covaxin was “safe and provides a robust immune response.
- “We’ll never approve anything if there is slightest of safety concern. The vaccines are 100% safe. Some side effects like mild fever, pain and allergy are common for every vaccine. It (people may get impotent) is absolute rubbish,” VG Somoni said.
- However, he also said that some side effects like mild fever, pain and allergy are common for every vaccine.
CME INDIA Discussion on 03/01/21
Dr Vijay Laxmi, Bengaluru (Known as mother of Indian Paediatric Echocardiography) agrees:
- A decisive turning point to strengthen a spirited fight! DCGI granting approval to vaccines of Serum Institute India and Bharat Biotech accelerates the road to a healthier and COVID-free nation.
- It would make every Indian proud that the two vaccines that have been given emergency use approval are made in India! This shows the eagerness of our scientific community to fulfil the dream of an Aatmanirbhar Bharat, at the root of which is care and compassion.
Dr Awadhesh K Singh, DM, Endo., Kolkata:
- If Covaxin was approved today based on the phase 2 data than it should have been approved 3 months earlier. Why wasted time?
- Recollect the same ICMR of March/April that advised HCQ/Ivermectin and what not – pre-exposure/ post exposure prophylaxis etc. etc. All are garbage 🗑 now!
- Whatever may be the logic but in the absence of even unpublished interim data it is so unscientific to give green signal. This put India in the same light (on international academia) like Chinese and Russians. I am really disappointed with such uncalled move. What was so hurry?
Dr Ambrish Mithal, DM, Endo., Delhi:
- I don’t know the inside story but it might just be as a backup in case they have to accelerate. I may be wrong. Till then more data will be available. The expert committee has some excellent scientists. Will try to find out. Expert committee is not ICMR alone
Dr Manoj Chawla, Diabetologist, Mumbai:
- Congratulations all on the approval of both vaccines. Am sure there will be debates about data on the same but nonetheless a step ahead with emergency approval
Dr Padmanabha Shenoy, DM Rheumatology, Cochin:
- Very good to see 2 vaccines being approved. Was wondering is there any phase 3 data for covaxin? If not, how can it be approved 🤔
- A good thought. maybe we need more vaccine candidates as mutant strain threatens to spread rapidly. but they could have approved and released interim data so that it would have looked more convincing. The oxford people recruited 35000 but published efficacy result of 11000 patient’s efficacy data (5000 in each arm). Covaxin has already recruited 23000. I am not sure whether they have done an interim analysis of the 10000 odds.
- Sputnik uses 2 different adenovectors ADV 26 during first one and Adv 5 during second
Dr Ambrish Mithal, DM Endo., Delhi:
- Yes, they should have waited for SOME peer reviewed publication. I agree. I would have done that.
Dr Harish Darla, Diabetologist, Mysore:
Is it possible that if the 1 st vaccine full doses given gives limited protection… then is different vaccine can be given to increase the chances of protection…? just a taught and would it be admissible
Dr Awadhesh K. Singh, DM, Endo., Kolkata:
That’s very unscientific and has not been studied anywhere.
Dr Harish Darla, Mysore:
Just a taught as PCV 13 and PPSV 23 are given on adults in some situations. Maybe it is unscientific in case of COVID.
Dr Manohar K N, Bengaluru:
- As HCPs are first to get Imagine the HCPs are down 😱 or it’s ineffective. And there is a wave. I am not happy about this. Few months wouldn’t have made a difference
Dr Awadhesh K Singh, Kolkata:
- This would have been still imaginable if AZ-Oxford vaccine was not available. But in the presence of one vaccine with all available evidence this move is not desirable!
- I think plan is same not to give Covaxin at first place. Even SEC has also said – reserved for mutant virus if any – need crystal clarity.
Dr S K Goenka, Begusarai:
- Amidst a few valid /invalid confusions about the new COVID vaccine, let’s treat this vaccine as the First-Generation Vaccine, like other drugs. As the time will pass, many more generations shall be available, which shall be more potent, safe and with long time protection.
Dr Jagdeeshan, Chennai:
- Today India approved 2 vaccines, like fda govt should upload all the documents submitted by both companies and minutes of meeting in dgci website for transparency and public scrutiny.
- We don’t have options either, now nearly 50 lakh shots of Pfizer n moderna administered already. Oxford vaccination going on in UK.
- In 1 month, time we can see if there is any acute or early side effects, but long-term effects we don’t know. And efficacy also we don’t know. How many months or how many years these vaccines give protection n al
- As there is no time, since it is pandemic. We have to agree that vaccines are rushed, that’s why emergency restricted usage approval. Not a routine approval.
- Unlike other vaccines this vaccination will have detailed record and beneficiaries will be kept under observation for 30 mins.
- Emergency use authorization – competent authority may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives. CBRN – chemical, biological, radiological and nuclear
Dr H D Sharan, Ranchi:
- No logic behind it. 1 day before the recommendation, the committee asked them to produce more data. They have not yet completed enrolment of volunteers for phase 3. If 2 phases of trial are enough, why the induction was delayed. Let us hope and pray that Indians will not have to face what happened with the Polio vaccine.
Dr Santosh Malpani, Diabetologist, Physician, Nanded:
After reading above discussion from all respected faculties the inference till this time
- Continue keep on continuing social distancing
- Continue wearing mask at all public places
- Wash hands repeated
- Control metabolic parameters
- Go on exercising
- Reduce stress
- Improve immunity
- Even if you take any good vaccine
Dr Ashok Kumar DM Neuro Ranchi:
- It appears new mutant strain has created a sense of great urgency. That may explain these Urgent/Fast/premature/panicky (depending upon one’s viewpoint) approvals.
- Clinical trial mode? A fig leaf cover? Phase 3 + 4 (post – marketing) combined? Needs clarification.
- Probably assumption is that Whole virus vaccine is likely to be more effective against mutants (when compared to very specific spike protein sequences — as mRNA or protein.
- Only time will tell if these actions of the Government and Medical establishment are Revolutionary or Ridiculous! Still, I think the Government making great effort and doing very well. We are waiting for Cavitied. Opposition is just being Irresponsible.
- With new mutant, situation may go “out of control ” (as in UK) in next several weeks. Extraordinary situations demand extraordinary response, often something which may be not acceptable normally. It is आपद्धर्म . Covaxin is a backup.
Dr Hemant Gupta, DM Gastro Varanasi:
IDEA: Corona has many new strains and probably we do not know how many more variants will come in near future. Pandemic or endemic Hep C affects millions of populations globally.
CME INDIA Learning Points
By Dr Shashank Joshi DM Endo, Dean ICP, Mumbai on 03/01/2021:
- Very valid points raised by all CME INDIA members.
- Let’s look at each limited restricted drug approval from 2 standpoints – one is safety and second is public health implications in a pandemic time.
- Serum Oxford
- Global phase 3 in place
- Indian phase 2/ 3 ongoing limited number 1600
- Immunogenicity data was awaited
- Have been given emergency use and continue clinical trial
- Bharat Biotech
- ICMR NIV phase 2 data are public domain under peer review
- Phase 3 15000 patient interim data presented to SEC based on which a limited research mode EUA has been granted
- Zydus Cadilla
- Phase 2 over
- Phase 3 commenced
- DRL Sputnik on going
- Pfizer did not appear before SEC for reasons best known to them
- 1 and 2 are having efficacy more than 50 percent and storage condition cold chain better than mRNA platform economical and safety data is possibly best in inactivated virion followed by the chimpanzee adenovector
- Possibly due to pandemic a decision was taken to fast track already fast-tracked process to make it available for population
Is it safe?
- Possibly yes
Is it effective?
- More than 50 percent
Does it need vigilance and research mode?
Does it need more data?
- Yes, it has to continue and publish in peer reviewed journals
- Oxford will be ready and out for use.
- Bharat Biotech use will still be in research mode in an open label way. It is going to be continued in a clinical trial mode only that’s exactly what has been told.
- Only COVIDshield will be formally available.
- Cadila will be in pure phase 3 mode.
Let’s hope we can vaccinate all health care workers and COVID Frontline with Oxford alone as serum claims to have stockpiles of the same
CME INDIA Tail Piece
Your duty to get vaccinated (WHO)
- When we get vaccinated, we aren’t just protecting ourselves, but also those around us. Some people, like those who are seriously ill, are advised not to get certain vaccines – so they depend on the rest of us to get vaccinated and help reduce the spread of disease.
- During the COVID-19 pandemic, vaccination continues to be critically important. The pandemic has caused a decline in the number of children receiving routine immunizations, which could lead to an increase in illness and death from preventable diseases.
- WHO has urged countries to ensure that essential immunization and health services continue, despite the challenges posed by COVID-19?
- It’s too early to know if COVID-19 vaccines will provide long-term protection. Additional research is needed to answer this question.
- However, it’s encouraging that available data suggest that most people who recover from COVID-19 develop an immune response that provides at least some period of protection against reinfection – although we’re still learning how strong this protection is, and how long it lasts.
- Most COVID-19 vaccines being tested or reviewed now are using two dose regimens.
Govt of India Update dated 03/01/2021
- The Subject Expert Committee (SEC) has reviewed the data on safety and immunogenicity of the vaccine and recommended for grant of permission for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, to have more options for vaccinations, especially in case of infection by mutant strains.
- The clinical trial ongoing within the country by the firm will continue. M/s Cadila Healthcare Ltd., has developed a Novel Corona Virus-2019-nCov-Vaccine using DNA platform technology. The firm-initiated Phase-I/II clinical trial in India in more than 1000 participants which is ongoing. The interim data suggests that the vaccine is safe and immunogenic with three doses when administered intradermally. Accordingly, firm has sought permission to conduct PhaseIII clinical trial in 26000 Indian participants, which has been recommended by the Subject Expert Committee.
- M/s Serum and M/s Bharat Biotech vaccines have to be administered in two doses. All the three vaccines have to be stored at 2-8° C.
- After adequate examination, CDSCO has decided to accept the recommendations of the Expert Committee and accordingly, vaccines of M/s Serum and M/s Bharat Biotech are being approved for restricted use in emergency situation and permission is being granted to M/s Cadila Healthcare for conduct of the Phase III clinical trial.
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Excellent but application of research to
People guidelines for injection and mgt thereafter l
The Bharat Biotech vaccine, developed in collaboration with ICMR and NIV (Pune) is a Whole Virion Inactivated coronavirus vaccine. “The firm has generated safety and immunogenicity data in various animal species such as mice, rats, rabbits, Syrian hamster, and also conducted challenge studies on non-human primates (Rhesus macaques) and hamsters. All these data has been shared by the firm with CDSCO. Phase I and Phase II clinical trials were conducted in approx.800 subjects and the results have demonstrated that the vaccine is safe and provides a robust immune response. The Phase III efficacy trial was initiated in India in 25,800 volunteers and till date, 22,500 participants have been vaccinated across the country and the vaccine has been found to be safe as per the data available till date,” it said.
What does the 70% efficacy mean? Does it mean that it will be effective in 70% population getting vaccine or there is 70% chance of not getting infected by the virus
We as HCW will form the largest participants of phase 3/4 combined clinical trials ever taken up. But as in clinical trials, enrolment is voluntary. But enrollment should be opened to other groups like leaders in all fields to increase and infuse confidence. Let all who are involved in the approval process, development and manufacturing also volunteer themselves and show their conviction for their decisions and set an example.
How the Vaccine were tested and then tried on human beings:-
The most commonly used vaccines have been around for decades, with millions of people receiving them safely every year. As with all medicines, every vaccine must go through extensive and rigorous testing to ensure it is safe before it can be introduced in a country.
An experimental vaccine is first tested in animals to evaluate its safety and potential to prevent disease. It is then tested in human clinical trials, in three phases:
In phase I, the vaccine is given to a small number of volunteers to assess its safety, confirm it generates an immune response, and determine the right dosage.
In phase II, the vaccine is usually given hundreds of volunteers, who are closely monitored for any side effects, to further assess its ability to generate an immune response. In this phase, data are also collected whenever possible on disease outcomes, but usually not in large enough numbers to have a clear picture of the effect of the vaccine on disease. Participants in this phase have the same characteristics (such as age and sex) as the people for whom the vaccine is intended. In this phase, some volunteers receive the vaccine and others do not, which allows comparisons to be made and conclusions drawn about the vaccine.
In phase III, the vaccine is given to thousands of volunteers – some of whom receive the investigational vaccine, and some of whom do not, just like in phase II trials. Data from both groups is carefully compared to see if the vaccine is safe and effective against the disease it is designed to protect against.
Once the results of clinical trials are available, a series of steps is required, including reviews of efficacy, safety, and manufacturing for regulatory and public health policy approvals, before a vaccine may be introduced into a national immunization programme.
Following the introduction of a vaccine, close monitoring continues to detect any unexpected adverse side effects and further assess effectiveness in the routine use setting among even larger numbers of people to continue assessing how best to use the vaccine for the greatest protective impact.