The Story Behind the FDA Approval of Pfizer’s Covid Vaccine

On 23^rd August, the United States Food and Drug Administration authorised the first COVID-19 vaccine. The vaccine was previously known as the Pfizer-BioNTech COVID-19 Vaccine. It will now be marketed under the brand name Comirnaty (koe-mir'-na-tee). The vaccine will be used for the prevention of COVID-19 disease in individuals 16 years of age and older.

Today, we'll go over some points which are pertaining with the USFDA's approval of Pfizer's Covid vaccine.

First and foremost, an introduction to the USFDA is required, even if most viewers of this channel are aware of this. The second, and probably more interesting, issue to consider is how long it typically takes for a medicine to be approved by the USFDA. The third and most significant topic to cover is the USFDA's drug development and approval process. Last but not least, does FDA approval guarantee the safety of a drug?

An Introduction to The USFDA:

The USFDA is a government regulatory agency within the U.S. Department of Health and Human Services.  The Center for Drug Evaluation and Research (CDER) is a science-led body under the United States Food and Drug Administration (FDA) which is in charge of reviewing the drug approval process before a drug is marketed. The CDER and FDA conduct a thorough examination of each drug with the help of an independent team of clinicians and scientists who assess the drug's safety, efficacy, and labelling. Following approval, the FDA continues to monitor new pharmaceutical products to ensure they remain safe and effective.

Before making a decision, the FDA does not test the medicine itself. However, as part of the approval procedure, the agency inspects the facility where the medicine would be made. Vaccines and biologics follow the same basic route as that of pharmaceuticals.

 How Long It Typically Takes For A Medicine To Be Approved By The USFDA:

The entire research, development, and approval procedure can take between 12 and 15 years. Only five compounds out of every 5,000 that undergo preclinical testing make it to human testing. Only one of these five compounds that goes through human trials is approved. According to the Tufts Center for the Study of Drug Development, it costs a manufacturer more than $2.6 billion to bring a new drug from the laboratory to the pharmacy shelf.

However, in 1992, the Prescription Drug User Fee Act (PDUFA) was passed in the United States, allowing the FDA to collect payments from corporations in order to speed the drug-approval process. According to the FDA, PDUFA has enabled the Food and Drug Administration to provide access to innovative drugs as quickly as or faster than anyplace else in the world. Since the passage of PDUFA in 1992, more than 1,000 medicines and biologics have entered into the market.

The act (PDUFA) establishes two approval timelines: (1) Standard Review and (2) Priority Review. The purpose of standard review is to complete the approval process for a medicine in 10 months. This type of evaluation is given to a medicine that provides little to no improvement over other therapies already available on the market. Priority review is a for medicines that produce significant advancements in treatment or provide treatment where no one previously existed. The FDA aims to complete the drug approval procedure in six months.

Furthermore, the FDA provides an accelerated approval pathway for selective medications which are used to treat serious and life-threatening conditions for which there is no suitable treatment. One disadvantage of the accelerated approval process is that it allows a New Drug Application to be granted before the drug's effectiveness are fully tested. This step is however normally required.

The Pfizer-BioNTech vaccine may have been licenced through this approach without being tested for efficacy. Virologists are concerned about the vaccine's unknown side effects and the perplexed durability assumption, in which no one can guarantee how long the vaccination will be effective in protecting against Covid-19. 

The USFDA's drug development and approval process.

Drug companies are constantly analysing thousands of chemicals in search of those with medicinal promise. The producer is known as preclinical testing which completes the drug's synthesis and purification and limited animal testing. Preclinical testing takes nearly six to seven years. Out of the 5,000 compounds evaluated, approximately five will appear promising enough. This will prompt the company to submit an Investigational New Drug Application (IND). If the IND is approved by the FDA and by an Institutional Review Board, the manufacturer may begin the first stage of development.

The IND stage comes next. The IND stage is divided into three phases. In phase I, clinical trials are undertaken with healthy people to determine the drug's basic characteristics and safety profile in humans. The medicine often remains in this stage for one to two years. In phase II, efficacy trials begin when the medicine is provided to volunteers from the target population. At the conclusion of phase II, the manufacturer meets with FDA officials to discuss the development process, ongoing human testing, any concerns the FDA may have, and the guidelines for phase III trial, which is often the most comprehensive and expensive stage of drug development. The IND stage lasts around seven years.

When phase III is completed, the manufacturer submits a New Drug Application (NDA). The NDA review process normally takes one to two years. The overall time for drug development and approval is around nine years (including the stages of IND and NDA). During the NDA stage, the FDA consults expert advisory committees to obtain a broader range of advice on drug safety, efficacy, and labelling. When the medicine is approved, it can be marketed with FDA-approved labelling. The FDA also collects safety data as the drug is taken and adverse events are recorded. FDA may seek modifications in labelling or issue statements in media when new contraindications emerge. If adverse effects appear to be systematic and serious, the FDA may withdraw a product from the market.

Here, I'd like to share some fascinating statistics with my readers. In 1980, the typical drug was subjected to thirty clinical trials involving approximately 1500 participants to get FDA’s approval. By the mid-1990s, the typical drug had to go through more than sixty clinical trials involving approximately 5,000 individuals. However, in the case of Pfizer's Covid vaccine, the FDA approved an Emergency Use Authorization (EUA) on December 11, 2020, based on only one clinical trial. To support the FDA's approval decision, the FDA reviewed updated data from the same clinical trial which supported the Emergency Use Authorization in December last year and included a longer duration follow up in a larger clinical trial population. As a result, it cannot be completely ruled out that the FDA's clearance of Pfizer's Covid vaccination was flawed.

Does FDA approval guarantee a drug's safety?

According to the FDA’s website, the Center for Drug Evaluation and Research (CDER) is to ensure that the drugs marketed in the United States of America are safe and effective. But, CDER does not test drugs. The Center’s Office of Testing and Research conducts limited research in the areas of drug quality, safety and effectiveness. It is the responsibility of the company to test a drug and submit evidence that it is safe and effective. Such data provided by the drug manufacturing company along with the proposed labelling are reviewed by a team of CDER physicians, scientists, chemists, pharmacologists and other scientists.

According to an article titled "Misplaced Trust" published in drugwatch, FDA approval does not guarantee safety. Critics say, Bif Pharma funds FDA reviews of new drugs, creating a conflict of interest. The agency is too focused on approving drugs to appease Big Pharma and it lacks the proper authority and funding to protect the public. 

It's now time to wrap up today's discussion. Those who were celebrating the FDA's approval of Pfizer's vaccine as a breakthrough in the fight against Covid-19 must have come to a halt after reading this.

@pradipsinterpretations

The Importance of Freedom of Thoughts in Independent India

 

Where the mind is without fear and the head is held high;

   Where knowledge is free;

   Where the world has not been broken up into fragments by narrow domestic walls;

   Where words come out from the depth of truth;

   Where tireless striving stretches its arms towards perfection;

   Where the clear stream of reason has not lost its way into the dreary desert sand of dead habit;

   Where the mind is led forward by thee into ever-widening thought and action

   Into that heaven of freedom, my Father, let my country awake.

        

                                       -- Rabindranath Tagore

During the proceeding to hear a slew of petitions demanding a court-monitored independent investigation into the alleged Pegasus snooping, a Supreme Court bench led by Chief Justice of India repeatedly asked the solicitor general whether the government would come clean about the purchase or use of Pegasus. On 17^th of August, the Supreme Court issued a notice to the Centre on the petitions brought before it regarding the deployment of the Pegasus malware against Indian citizens. The subject will be revisited in 10 days. Incidentally, India celebrated its 75th year of independence two days before this court case.

From the acceptable into the intolerable; from a recognized democracy to a scorn authoritarianism; from unrestrained freedom to infamous system of surveillance; from a decent confidentiality to a mockery of privacy …… this is how India has entered into its 75^th year of independence. The political critiques, free thinkers and investigative journalists who are called as the messengers of democracy are deeply feared by the increasingly insecure ruler. They become the targets of snooping anytime, anywhere and by all means. It is not a surprise that the messenger of democracy would be placed under deep surveillance because the ruling class not only lives on fear but often under perceived non-existent threats. That is why, for the ruler, a surveillance system is necessary to build up.

In a recognised democracy, the government’s invasion of privacy to curb the human rights is unacceptable. Revelations of Pegasus, the latest in technology to hack journalists, is an example of expansive global design. From Mexico to Rwanda to Saudi Arabia, Governments across the world have used Pegasus to spy their own citizens, especially journalists, human rights campaigners and other social activists.

The Pegasus case poses an unprecedented challenge to India. The emergence of surveillance state shows that the present ruling dispensation has very little or no regard for democracy or its institutions respond to it. India is widely regarded as the world's largest democracy. Since its independence, India has suffered from a number of inadequacies, some of which are fundamental to human progress. India ranks below average in the global hunger index, per capita health spending, human capital index, literacy rate, education index, world happiness index, human development index, social progress index, gender inequality index, and global youth development index. However, the right to free speech and expression has always been prioritised. The country has always upheld democratic norms. Since Narendra Modi's election as Prime Minister of India in May 2014, India's liberal democracy index score has plummeted along with all the development indices. India's freedom of expression index has also drastically declined. There has been a sharp fall in India’s civil society participation index score. The party that controls the present government at the centre, envisions a country devoid of pluralism. This has major implications for the country's democratic culture and democratic institutions.

Freedom of expression is a universal human right. It is not the politician's prerogative. It is also not a journalist's prerogative. In their daily work, journalists are merely practising every citizen's right to free speech. In any civilised society, it is essential for all citizens to have not just the right to free speech, but also the right to accurate information. The freedom of the press can fulfil citizens' entitlement to truthful information. A free press is essential in any democratic society. It keeps those in power accountable. The press gives a forum for a diverse range of voices to be heard. It is the public's watchdog, activist, and protector.

Even before the Pegasus Scandal broke out, India had been witnessing a serious decline in press freedom. The government’s direct and indirect assaults on media-persons partially succeeded in creating a climate of self-censorship. Gradually, India was turning out to be a dangerous place for journalists to work freely and without fear.

In 2020, at least 226 journalists and two media houses were targeted, 13 were killed, 37 were arrested or detained, 64 had FIRs registered against them. In addition, show-cause notices or summons were issued against 13 journalists and one newspaper, 101 journalists were subjected to physical assault or online threats or their houses and family members were attacked. This is according to the “Indian Press Freedom Report 2020”.

Most of the journalists, attacked during the last year, were from Uttar Pradesh, followed by Maharashtra, Jammu and Kashmir, Delhi and Karnataka. These included 12 women journalists who had faced physical violence, online harassment and threats. During the first tenure of the Modi government, between 2014 to 2019, more than 200 serious attacks on journalists took place and 40 journalists were killed in the same period. In 2020, as per the World Press Freedom Index, India ranked 142 out of 180 countries. Reporters Sans Frontiers called India “the most” dangerous country in the world for journalists.

This year, in the month of May, during the India-European Union summit, the Committee to Protect Journalists (CPJ) submitted a letter to the European Union. The letter highlighted the hostile situation under which journalists in India are working and requested European Union to urge the Indian government not to interfere with the journalists or retaliate against them who were doing their jobs.

Several petitions have been filed before the Supreme Court in response to the Pegasus revelations. The petitioners have asked the Union of India to divulge whether the government or any of its agencies purchased Pegasus and used it for spying in any way. They have also questioned the ramifications of such a hack and whether it was an attempt by agencies and groups to censor and chill the exercise of free speech and criticism in India.

The Pegasus hack is a direct attack on communicational, intellectual, and informational privacy, putting real privacy practice in these contexts at risk. The right to privacy includes the ability to use and control one's mobile phone or electronic equipment. Any interception by hacking or tapping is a violation of this fundamental right. If the attack did occur, it was an unacceptable infringement of the right to privacy, which has been recognised as a basic right. India has an unprecedented difficulty as a result of the Pegasus issue. The future will be determined by how the nation and its institutions react to it.

The right to privacy, free speech, and freedom of expression should be recognised as essential human rights. This should be safeguarded in order to maintain India's democratic character in its 75th year of independence.

@pradipsinterpretations

Looking for the finest Covid-19 vaccine?

 The new phase of centralized free COVID-19 vaccination has begun from June 21st, and in a historic feat, 80,95,314 doses were provided on the first day of the new phase of COVID-19 vaccination. This is the world's largest single-day number of jabs. However, having a suitable and effective vaccine is just as crucial as having the free vaccines.

Which vaccine against Covid-19 is the most effective? For the past two and a half months, this has been the most frequently asked question about Covid-19. To be honest, finding a correct and legitimate response to this has been pretty difficult. In this episode, we'll attempt to solve this complex and challenging question. Let me request my viewers to watch this video patiently till the end. We'll use the prestigious medical journal “The Lancet" to discuss the efficacy of the several Covid-19 vaccines available in the market.

Before we go into the specifics of vaccine efficacy, let's have a quick look at the current immunisation status of the developed countries. Perhaps, that will help us to understand the issue in a better way.

To begin, let’s have a look at how the US vaccine rollout looks right now. According to the TIME, USA, around 44% of Americans have received both doses of the Two-shot Pfizer and Moderna drugs or a single injection of the one-dose Johnson&Johnson version of vaccine. Please note that the US has entered into the sixth month of its Covid-19 vaccine rollout. If you consider to add on the population those who have received only the first dose of Pfizer or Moderna – the total figure stands at just 50%.

On 29^th April, the Cable News Network (CNN) reported that the vaccine manufacturing companies changed shipment sizes as coronavirus vaccine demands declined. What does this actually mean? The statement of Freeman would perhaps clarify this. Lori Tremmel Freeman, CEO of County and City Health Officials told CNN, “Many of our health departments, especially those in rural America, are providing feedback that they either need smaller dosage vials or we will have to contend with waste.” This statement of Freeman came in the background of a CNN poll conducted by SSRS which states that at least 25% Americans say that they will not get the shot of vaccine.

Because of the widespread public opposition, state and municipal officials in the United States of America have asked vaccine makers to reduce the size of vaccination vials. As a result, Pfizer announced that it would offer lower package sizes. The shipment size was lowered from a pack containing 1,170 doses to a pack containing just 450 doses. The Executive Director of the Association of Immunization Managers, on the other hand, believes that a push should be made to change vaccination practises. Gradually, we've come across a few different forms of such push!

 

Free beer and marijuana are being offered by the US government in exchange for Covid-19 vaccine. The state's liquor and cannabis board recently stated that state-licensed cannabis businesses will be able to provide adults with "free joints" after their first or second immunisation at participating outlets. Across the United States, health authorities and a number of private organisations are implementing such efforts, which are aimed mostly at the younger generation. The viewers of this channel must decide whether or not it is justified to give out free beer and marijuana to young people in order to advertise the Covid-19 vaccine. In any case, while Indians have been queuing since midnight and fighting one other over a Covid jab, the United States of America is attempting to entice its countrymen to do the same.

 

Let's have a look at the situation of cumulative vaccine uptake in European Union (EU) and European Economic Area (EEA) countries (EEA). As of June 17th, 2021, less than 30% of adults in European countries have been fully vaccinated against Covid-19, with roughly 54% receiving only a single dose of the vaccine. There is a bold assertion that some indicators of reduced Covid-19 transmission can be found in Europe as a result of immunisation programmes across the continent. But, to what extent is this true? Let's take a look at some of the countries' immunisation data.

 

Bulgaria and Finland, for example, had completed immunisation for roughly 10% of their population as of May 30, 2021. Around 18 percent in Sweden, 20 percent in Austria, Norway, and France, and 21 to 23 percent in the Netherlands, Germany, Belgium, Portugal, Italy, and Spain. Almost all European countries are in a similar situation. Malta is the only European country with a vaccination rate of around 49 percent. Hungary is next, with roughly 47% of its vaccinations completed.

 

But what are the likely causes of Europe's immunisation program's dismal results? Viewers will notice that vaccine dose availability was never an issue. Take Finland as an example. The producers provided around 76 Covid-19 vaccination doses for every 100 people in Finland. However, only about 11 people out of every 100 in Finland have received the Covid vaccine. Take a look at the chart, which shows the immunisation status of some of Europe's most advanced countries.

 

Sl No.	Name of the country		Vaccinated	Availability
			(per 100	(per 100
	(Status up to 30 May, 2020)		population)	population)
1	Bulgaria		9.70	55.20
2	Finland		10.90	75.80
3	Sweden		18.20	79.90
4	Austria		20.70	70.00
5	Norway		20.70	76.90
Sl No.	Name of the country		Vaccinated	Availability
			(per 100	(per 100
			population)	population)
6	France		20.90	76.40
7	Netherlands		21.00	81.30
8	Germany		21.10	79.90
9	Belgium		22.90	75.90
10	Portugal		23.10	75.90
Sl No.	Name of the country		Vaccinated	Availability
			(per 100	(per 100
			population)	population)
11	Italy		23.50	75.10
12	Spain		23.60	71.90
13	Hungary		44.70	166.70

 

It is quite clear that despite substantial vaccine supply, the vaccination push in some of Europe's most sophisticated countries has yet to achieve sufficient success.

 

When we look at Australia and Japan, the scenario for vaccine proponents is much less favourable. As of June 17th, 2021, only approximately 3% of Australians had had a full vaccination, while about 21% had received only one dosage. As of June 17th, little over 6% of people in Japan had been fully vaccinated, while roughly 16% had just received one dosage.

 

The poor performance of many affluent countries when it comes to Covid-19 vaccination raises concerns about the vaccines' efficacy. Regarding the FDA approval of Covid-19 vaccinations, viewers should be aware that “Currently, no coronavirus vaccine is fully approved by the FDA. All the vaccines were given emergency use authorization only.

 

FDA approval of a drug, which requires a rigorous and structured process, means that data on the drug’s effects have been reviewed by the Centre for Drug Evaluation and Research which rules on whether the drug’s benefits outweigh its known and potential risks. The fact that none of the Covid-19 vaccines have received FDA clearance, demonstrates that the efficacy of such candidate vaccines could not overcome their potential dangers. That is likely the most important factor for individuals lack of interest in the Covid-19 vaccination in developed countries.

 

With this background in mind, now, we'll use Lancet to discuss the efficacy of Covid-19 vaccines. The study that we will discuss was published in Lancet Microbe on April 10th of this year.

 

At present, approximately 96 COVID-19 vaccines are at various stages of clinical development and we have the interim results of four vaccines which were published in scientific journals. These vaccines are – the Pfizer–BioNTech vaccine, the Moderna vaccine, the AstraZeneca– Oxford vaccine and the Gamaleya [Sputnik V] vaccine. We also have three studies through the US Food and Drug Administration (USFDA) briefing documents on the Pfizer–BioNTech, Moderna and Johnson & Johnson vaccines. Excerpts of these results have been widely communicated and debated through press releases and media, more than the scientific community and thus sometimes in misleading ways. Attention has focused on vaccine efficacy by comparing the reduction of the number of symptomatic cases. However, understanding the efficacy and effectiveness of vaccines in totality is less straightforward than it might seem.

 

Vaccine efficacy is generally reported as a relative risk reduction (RRR). What is relative risk reduction? Relative risk reduction is how much risk is reduced in an experimental group compared to a control group. For example, we have two groups of people. One group has been vaccinated (which is termed as experimental group) and the other group has not been vaccinated (and, is termed as control group). Let’s say, in the control group, those who were not vaccinated, 20% people died of Covid-19 and in the experimental group 5% people died of Covid-19. 20% is called as control group event rate (CER) and 5% is called as experimental group event rate (EER).

 

The formula to derive the relative risk reduction is:

RRR = (CER-EER)/CER

            = (0.20-0.05)/0.05

            = (0.15)/0.05

            = 0.3

            = 30%

In other words, the death rate in the vaccinated group is 30% less. Although relative risk reduction provides some information about risk, but it does not say anything about the actual odds of what is happening. RRR considers only participants which varies between populations and over time. Therefore, when you see a headline in the media like relative risk reductions of 95% for the Pfizer–BioNTech, 94% for the Moderna, 90% for the Sputnik V, 67% for the Johnson &Johnson, and 67% for the AstraZeneca–Oxford vaccines, the report is usually referring to relative risk which is half-truth. This leaves us with the unanswered question as to whether a vaccine with a given efficacy in the study population will have the same efficacy in another population with different levels of background risk of COVID-19. But this is an important question because transmission intensity varies between countries, affected by factors such as public health interventions and virus variants.

 

To derive an estimate of vaccine effectiveness, the absolute risk reduction (ARR) has to be calculated. Absolute risk reduction which is also called as risk difference is the absolute difference between the control group and the experimental group. While the relative risk reduction considers only the participants of the trial who could benefit from the vaccine, the absolute risk reduction (ARR), considers the whole population in terms of the difference between attack rates with and without a vaccine. Subtracting the Experimental Event Rate from the Control Event Rate yields the absolute risk reduction. If we take the previous example of relative risk reduction, the absolute risk reduction will be:

CER-EER = 0.20 – 0.05 = 0.15 = 15%

 

When computing the absolute risk reduction, the relative risk reduction of 30% was reduced to only 15%.

 

According to the Lancet Microbe study, absolute risk reductions are often overlooked, because they have a significantly smaller effect size than relative risk reductions. To understand this, let’s have a look at this chart:

 

Name of the Vaccine	Relative Risk Reduction              (RRR)	Absolute Risk Reduction              (ARR)
AstraZeneca–Oxford	67%	1.3%
Moderna	94%	1.2%
Johnson & Johnson	67%	1.2%
Gamaleya (Sputnik V)	90%	0.93%
Pfizer–BioNTech	95%	0.84%

 

With the use of only Relative Risk Reductions, and omitting Absolute Risk Reductions, the reporting bias has been introduced by the vaccine manufacturers, which affected the interpretation of vaccine efficacy. When communicating about vaccine efficacy, a full picture of what the data actually show is important. Comparisons should be based on the combined evidence that puts vaccine trial results in context and not just looking at one summary measure. Ranking the vaccines by their reported efficacies based only on the relative risk reductions is unfair. These studies that measured the efficacy and effectiveness of vaccines are based on the prevention of mild to moderate COVID-19 infection; they were not designed to conclude on prevention of hospitalisation, severe disease, or death, or on prevention of infection and transmission potential. Assessing the suitability of vaccines must consider all indicators, involving safety, deployability, availability, and costs.

 

Unfortunately, the vaccines that are currently available on the market do not meet these critical requirements. Therefore, we will have to wait for the right vaccine to arrive to combat Covid-19.

@pradipsinterpretations