Explainer-When and how will COVID-19 vaccines become available?

By Julie Steenhuysen and Carl O’Donnell

NEW YORK (Reuters) – Pfizer Inc with partner BioNTech SE and Moderna Inc have released trial data showing their COVID-19 vaccines to be about 95% effective at preventing the illness, while AstraZeneca Plc this week said its vaccine could be up to 90% effective.

If regulators approve any of the vaccines in coming weeks, the companies have said distribution could begin almost immediately with governments around the world to decide who gets them and in what order. The following is an outline of the process:

WHEN WILL COMPANIES ROLL OUT A VACCINE?

Pfizer, Moderna and AstraZeneca have already started manufacturing their vaccines. This year, Pfizer said it will have enough to inoculate 25 million people, Moderna will have enough for 10 million people and AstraZeneca will have enough for more than 100 million people.

The U.S. Department of Defense and the Centers for Disease Control and Prevention (CDC) will manage distribution in the United States, likely starting in mid-December with an initial release of 6.4 million doses nationwide.

UK health authorities plan to roll out an approved vaccine as quickly as possible, also expected in December.

In the European Union, it is up to each country in the 27-member bloc to start distributing vaccines to their populations.

WHO WOULD GET AN APPROVED VACCINE AND WHEN IN THE UNITED STATES?

Upon authorization from the U.S. Food and Drug Administration, the CDC has said first in line for vaccinations would be about 21 million healthcare workers and 3 million residents in long-term care facilities.

Essential workers, a group of 87 million people who do crucial work in jobs that cannot be done from home, are the likely next group. This includes firefighters, police, school employees, transportation workers, food and agriculture workers and food service employees.

Around 100 million adults with high-risk medical conditions and 53 million adults over the age of 65, also considered at higher risk of severe disease, are the next priority.

U.S. public health officials said vaccines will be generally available to most Americans in pharmacies, clinics and doctors offices starting in April so that anyone who wants a shot can have one by the end of June.

It is unclear when a vaccine will be available for children. Pfizer and BioNTech have started testing their vaccine in volunteers as young as 12.

WHEN WILL A VACCINE BE AVAILABLE IN OTHER COUNTRIES?

The European Union, the United Kingdom, Japan, Canada and Australia are all running rapid vaccine regulatory processes.

Many of AstraZeneca’s doses this year are expected to go to the United Kingdom, where health officials have said that if approved they could begin vaccinating people in December. At the top of their list is people living and working in care homes.

In Europe, the E.U. drugs regulator has said it could rule on the safety of a COVID-19 vaccine in December.

Most countries have said the first vaccines will go to the elderly and vulnerable and frontline workers like doctors.

Countries say they are buying vaccines via the European Commission’s joint procurement scheme, which has deals for six different vaccines and nearly 2 billion doses.

Delivery timelines vary and most countries are still drawing up plans for distributing and administering shots.

Italy expects to receive the first deliveries of the Pfizer-BioNTech shot and AstraZeneca’s shot early next year. Spain plans to give vaccines in January.

In Bulgaria, the country’s chief health inspector expects the first shipments in March-April. Hungary’s foreign minister said doses will land in the spring at the earliest.

Germany, home to BioNTech, expects to roll out shots in early 2021 with mass vaccination centers in exhibition halls, airport terminals and concert venues. It will also use mobile teams for care homes. Front-line healthcare workers and people at risk for serious COVID-19 are expected to get inoculated first.

WHEN WILL DEVELOPING COUNTRIES HAVE ACCESS TO VACCINES?

COVAX, a program led by the World Health Organization and the GAVI vaccine group to pool funds from wealthier countries and nonprofits to buy and distribute vaccines to dozens of poorer countries, has raised $2 billion.

Its first goal is to vaccinate 3% of the people in these countries with a final goal of reaching 20%. It has signed a provisional agreement to buy AstraZeneca’s vaccine, which does not require storage in specialized ultra cold equipment like the Pfizer vaccine.

It is expected but not certain that less wealthy countries in Africa and South East Asia, such as India, will receive vaccines at low or no cost under this program in 2021. Other countries such as those in Latin America may buy vaccines through COVAX. Several are also striking supply deals with drugmakers.

HOW MUCH WILL IT COST?

Vaccine makers and governments have negotiated varying prices, not all of which are public. Governments have paid from a few dollars per AstraZeneca shot to up to $50 for the two-dose Pfizer regimen. Many countries have said they will cover the cost of inoculating their residents.

(Reporting by Carl O’Donnell and Julie Steenhuysen; Additional reporting by Michael Erman in New York, Caroline Copley in Berlin, Francesco Gaurascio in Brussels, Josephine Mason in London, Krisztina Than in Budapest and Tsvetelia Tsolova in Sofia; Editing by Caroline Humer and Bill Berkrot)

Super-cold container firm va-Q-tec expands to meet COVID-19 vaccine demand

By Ilona Wissenbach

FRANKFURT (Reuters) – Cold-storage specialist va-Q-tec is significantly expanding its fleet of 2,500 rental containers to meet growing demand to transport COVID-19 vaccines that need to be kept as low as -70 degrees Celsius (-94°F), its chief executive said.

The German company is in talks with all the major pharmaceutical manufacturers of COVID-19 vaccines, CEO Joachim Kuhn told Reuters in an interview.

Kuhn said the company would “significantly expand” its fleet of rental containers in the coming year. He did not specify how many extra containers were planned, though said it would not be to the extent of doubling the fleet.

Va-Q-tec is among a handful of high-end packaging providers who have found themselves in high demand as drugmakers and logistics firms prepare to transport such shots around the world. Its shares have risen by 230% this year, valuing the company at around $690 million.

The company’s turnover has increased by 30% annually over the past 10 years. “We expect this growth to continue in a similar form,” said the CEO, adding that global vaccine distribution might take several years.

“We are carefully increasing the number. With the market growing by more than 10% per year, we are not afraid that we will be left sitting on empty containers after corona.”

The Würzburg-based company completed a 25 million Swiss franc ($27.4 million) bond issue on Monday to help fund its expansion plans.

It manufactures “passive” containers, which use dry ice to keep the contents at ultra-cold temperatures for up to five or six days, as opposed to “active” containers that also use electric motors for cooling.

The vaccine candidate developed by Pfizer and BioNTech, which uses mRNA technology, needs to be kept at about -70 degrees Celsius, colder than the offerings from Moderna Inc and AstraZeneca PLC.

Kuhn said va-Q-tec had contracts with the world’s 20 largest airlines and major freight-forwarders. He said intercontinental transport with cargo flights was expected to be less of a problem than last-mile distribution on the road, given there was experience in transporting super-cold goods by air.

“To meet the demand for dry ice is not a big problem in our latitudes with sufficient regional production,” Kuhn said. “It will be a challenge in countries that do not have this infrastructure in Africa, Latin America or Russia.”

(Reporting by Ilona Wissenbach, Reuters TV; Writing by Jamie Freed; Editing by Pravin Char)

Airlines set to lose $157 billion amid worsening slump: IATA

By Laurence Frost

PARIS (Reuters) – Airlines are on course to lose a total $157 billion this year and next, their main global body warned on Tuesday, further downgrading its industry outlook in response to a second wave of coronavirus infections and shutdowns afflicting major markets.

The International Air Transport Association (IATA), which in June had forecast $100 billion in losses for the two-year period, said it now projects a $118.5 billion deficit this year alone, and a further $38.7 billion for 2021.

The bleak outlook underscores challenges still facing the sector despite upbeat news on development of COVID-19 vaccines, whose global deployment will continue throughout next year.

“The positive impact it will have on the economy and air traffic will not happen massively before mid-2021,” IATA Director General Alexandre de Juniac told Reuters.

Passenger numbers are expected to drop to 1.8 billion this year from 4.5 billion in 2019, IATA estimates, and will recover only partially to 2.8 billion next year. Passenger revenue for 2020 is expected to have plunged 69% to $191 billion.

“That’s by far the biggest shock the industry has experienced in the post-World War Two years,” IATA Chief Economist Brian Pearce said.

The forecasts assume significant re-opening of borders by the middle of next year, helped by some combination of COVID-19 testing and vaccine deployment.

IATA reiterated its call for governments to replace travel-stifling quarantine regimes with widespread testing programs.

“We are seeing states progressively coming to listen to us,” de Juniac said, citing testing initiatives underway in France, Germany, Italy, Britain, the United States and Singapore.

While some governments and airlines such as Australia’s Qantas say passengers are likely to require vaccination for long-haul travel, the approach is unlikely to work everywhere, de Juniac said.

“It would prevent people who are refusing (the vaccine) from travelling,” the IATA chief said. “Systematic testing is even more critical to reopen borders than the vaccine.”

Air cargo, a rare bright spot for the industry as the grounding of flights pushes freight prices higher, will likely see global revenue rise 15% to $117.7 billion this year despite an 11.6% decline in volume to 54.2 million tonnes, IATA said.

Some $173 billion in government aid has left recipients with debts that threaten to hobble future investment, it warned, and more bankruptcies are likely. Norwegian Air became the latest casualty on Nov. 18, when it filed for bankruptcy protection in Ireland.

The average airline now has enough liquidity to survive another 8.5 months, while some have just weeks, Pearce said. “I think we will get consolidation through some airline failures.”

(Reporting by Laurence Frost; Additional reporting by Johnny Cotton; Editing by Mark Potter and David Evans)

EU secures 160 million doses of Moderna’s COVID-19 vaccine

BRUSSELS (Reuters) -The European Union has struck a deal for up to 160 million doses of U.S. firm Moderna’s COVID-19 vaccine candidate, the head of the European Commission said on Tuesday, taking the EU’s potential stock of COVID-19 shots to nearly 2 billion.

Last week, Moderna said its experimental vaccine was 94.5% effective in preventing COVID-19, based on interim data from a late-stage clinical trial.

“I am happy to announce that tomorrow we will approve a new contract to secure another COVID-19 vaccine,” Ursula von der Leyen said, adding the deal “allows us to buy up to 160 million doses of a vaccine produced by Moderna.”

Actual purchases will be carried out by EU governments if the vaccine is approved by the EU’s drug regulator.

The delivery timeline is unknown. The doses would be enough to vaccinate 80 million people as the vaccine is expected to be administered in two doses.

In August the EU’s executive Commission, which co-leads talks with vaccine makers on behalf of member states, said it had held preliminary talks with Moderna over a deal for 80 million doses and an option for 80 million more.

The terms of the contract have not been disclosed.

An EU official involved in the talks told Reuters last week the EU was seeking a price below $25 per dose for Moderna’s vaccine..

But Moderna Chief Executive Stephane Bancel said on Sunday the company would charge governments between $25 and $37 per dose, depending on the amount ordered.

A spokesman for the Commission declined to comment on pricing.

It is the sixth supply deal the EU has negotiated with COVID-19 vaccine makers and takes the total number of doses secured by the bloc to 1.96 billion for its population of around 450 million.

Brussels has already struck deals with AstraZeneca, Pfizer-BioNTech, Sanofi-GSK, Johnson & Johnson and CureVac.

It is also in talks to buy U.S. firm Novavax’s potential COVID-19 vaccine.

(Reporting by Francesco Guarascio @fraguarascioEditing by Alexandra Hudson and Mark Potter)

Pfizer is first to apply for U.S. emergency use for COVID-19 vaccine

By Vishwadha Chander

(Reuters) – Pfizer Inc. said it will apply to U.S. health regulators on Friday for emergency use authorization (EUA) of its COVID-19 vaccine, the first such application in a major step toward providing protection against the new coronavirus.

The application to the U.S. Food and Drug Administration (FDA) comes just days after Pfizer and German partner BioNTech SE reported final trial results that showed the vaccine was 95% effective in preventing COVID-19 with no major safety concerns.

Pfizer’s shares rose 1.6% and BioNTech climbed 6% on the news that a vaccine could soon be available, raising hopes for the end of a pandemic that has claimed more than a quarter of a million lives in the United States and over 1.3 million worldwide.

The application also includes safety data on about 100 children 12-15 years of age. The company said 45% of U.S. trial participants are 56-85 years old.

If the data is solid, “we literally could be weeks away from the authorization of a 95% effective vaccine,” U.S. Health Secretary Alex Azar said on CBS’ “This Morning”.

The companies expect the FDA to grant the EUA by mid-December and said they will begin shipping doses almost immediately. Pfizer has said it expects to have 50 million vaccine doses ready this year, enough to protect 25 million people.

An FDA advisory committee tentatively plans to meet Dec. 8-10 to discuss the vaccine, a source familiar with the situation told Reuters, though the dates could change.

The final trial data showed the vaccine provided a similar level of protection across different ages and ethnicities – an encouraging result as the disease disproportionately hurts the elderly and minorities.

Of the 170 volunteers who contracted COVID-19 in Pfizer’s trial involving over 43,000 people, 162 had received only a placebo, meaning the vaccine was 95% effective, far higher than originally expected. U.S. FDA had set minimum bar for efficacy of 50%.

Pfizer said nearly 42% of global participants and 30% of U.S. participants in the Phase 3 study have racially and ethnically diverse backgrounds.

“Filing in the U.S. represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world and we now have a more complete picture of both the efficacy and safety profile of our vaccine,” Pfizer Chief Executive Officer Albert Bourla said in a statement.

Moderna Inc. is expected to be the next company to seek a U.S. emergency use nod for a COVID-19 vaccine. An initial analysis of data from its late-stage trial showed the vaccine was 94.5% effective. Final results and safety data are expected in the coming days or weeks.

Both the Pfizer/BioNTech and Moderna vaccines work using a new technology to trigger an immune response known as synthetic messenger RNA that can be produced at scale much more quickly than traditional vaccines.

Of dozens of drugmakers and research institutions racing to develop COVID-19 vaccines, the next late-stage data is expected to come from AstraZeneca Plc, which is working with the University of Oxford, in November or December.

Johnson & Johnson said it expects to have data needed to seek U.S. authorization for its experimental vaccine by February.

(Reporting by Vishwadha Chander in Bengaluru, additional reporting by Ankur Banerjee in Bengaluru and Doina Chiacu in Washington; Editing by Bill Berkrot, Shinjini Ganguli and Chizu Nomiyama)

FDA to make emergency use authorization data public for COVID-19 vaccines

(Reuters) – The U.S. Food and Drug Administration said on Tuesday it would make public reviews of all data and information regarding the emergency use authorization (EUA) granted to COVID-19 drugs and vaccines.

“Today’s transparency action is just one of a number of steps we are taking to ensure public confidence in our EUA review process for drugs and biological products, especially any potential COVID-19 vaccines,” FDA Commissioner Stephen Hahn said in a statement.

Hahn said all FDA drug and biological product centers intend, “to the extent appropriate and permitted by law,” to share information about scientific review documents supporting the issuance, revision or revocation of EUAs.

Countries around the world are racing to develop COVID-19 vaccines and treatments, and the rapid pace of development has had doctors and experts concerned about transparency and regulatory reviews.

The FDA said it recognizes disclosing such information would also contribute to the public’s confidence in the agency’s rigorous review of scientific data.

“We will also continue to follow the science and ensure that science remains the driver of the agency’s regulatory decision-making in our fight against COVID-19 and beyond on behalf of public health,” Hahn said.

(Reporting by Vishwadha Chander in Bengaluru; Editing by Sriraj Kalluvila)

Moderna says UK deal will supply COVID-19 vaccine from March

(Reuters) – Moderna Inc confirmed on Tuesday it had agreed to supply its COVID-19 vaccine candidate, mRNA-1273, to the United Kingdom starting from the beginning of March, as long as it succeeds in gaining local regulatory approval.

The company’s statement did not disclose other terms of the agreement, including the number of doses it agreed to supply.

UK Health Minister Matt Hancock told a news conference on Monday that the deal would see the U.S. startup, one of two vaccine makers who have so far published positive data on final-stage trials, supply five million doses from next spring.

Moderna on Monday said mRNA-1273 was 94.5% effective in preventing COVID-19 based on interim data from its late-stage clinical trial.

Britain’s Medicines and Healthcare products Regulatory Agency (MHRA) in October started a real-time review of the vaccine candidate, a process which allows for a faster approval of a treatment.

The company on Tuesday also said it was on track to deliver about 500 million doses per year and possibly up to 1 billion doses per year, beginning in 2021.

It has tied up with manufacturing partners Lonza of Switzerland and ROVI of Spain, for manufacturing and fill-finish outside of the United States, to supply the vaccine to Europe and other countries outside U.S.

(Reporting by Manojna Maddipatla in Bengaluru; Editing by Krishna Chandra Eluri and Patrick Graham)

Pfizer to start pilot delivery program for its COVID-19 vaccine in four U.S. states

(Reuters) – Pfizer Inc. has launched a pilot delivery program for its experimental COVID-19 vaccine in four U.S. states, as the U.S. drugmaker seeks to address distribution challenges facing its ultra-cold storage requirements.

Pfizer’s vaccine, which was shown to be more than 90% effective in preventing COVID-19 based on initial data, must be shipped and stored at -70 degrees Celsius (minus 94°F), significantly below the standard for vaccines of 2-8 degrees Celsius (36-46°F).

“We are hopeful that results from this vaccine delivery pilot will serve as the model for other U.S. states and international governments, as they prepare to implement effective COVID-19 vaccine programs,” Pfizer said in a statement on Monday.

It picked Rhode Island, Texas, New Mexico, and Tennessee for the program after taking into account their differences in overall size, diversity of populations, immunization infrastructure, and need to reach individuals in varied urban and rural settings.

The four states will not receive vaccine doses earlier than other states by virtue of the pilot, nor will they receive any differential consideration, Pfizer said.

The company expects to have enough safety data on the vaccine from the ongoing large scale late-stage trials by the third week of November before proceeding to apply for emergency use authorization (EUA).

Pfizer and its partner BioNTech SE have a $1.95 billion deal to supply 100 million doses of the vaccine to the U.S. government, which has an option to acquire up to an additional 500 million doses.

Earlier on Monday, rival Moderna Inc. said its experimental vaccine was 94.5% effective in preventing COVID-19 based on interim data from a late-stage trial, boosting hopes that vaccines against the disease may be ready for use soon.

Both the Pfizer and Moderna vaccines use a new technology called synthetic messenger RNA to activate the immune system against the virus.

(Reporting by Shubham Kalia in Bengaluru; Editing by Anil D’Silva and Richard Pullin)

Explainer – Shot in the dark: Early COVID-19 vaccine efficacy explained

By John Miller

ZURICH (Reuters) – This week has seen a flurry of good news from COVID-19 vaccine developers, with Pfizer Inc. and BioNTech SE trumpeting early data indicating their mRNA candidate is more than 90% effective.

A Russian project came out a day later, touting 92% efficacy for the Sputnik V candidate, named after the Soviet-era satellite, based on a smaller data set.

HOW DO MANUFACTURERS ARRIVE AT EFFICACY NUMBERS?

In Pfizer’s case, it waited until 94 volunteers in its late-stage clinical trial of more than 43,500 people – half got the vaccine, the other half got a placebo – tested positive after developing symptoms.

For 90%-plus efficacy, no more than eight people among those who tested positive had received the vaccine, with the rest having received the placebo.

“Roughly speaking, it’s probably around eight to 86 cases in the treated and placebo groups,” David Spiegelhalter, a Cambridge professor of risk and an expert in statistics, told Reuters.

“You don’t need a lot of fancy statistical analysis to show that this is deeply impressive. It just hits you between the eyes.”

In Russia, Sputnik V-developer Gamaleya Institute reached its preliminary 92% efficacy figure based on 20 illnesses in 16,000 volunteers as its late-stage trial progresses. It aims to reach 40,000 people.

Of the 16,000 people, about quarter got the placebo.

“It suggests that there is some effect, but it’s insufficient to estimate the magnitude of it,” Spiegelhalter said.

HOW MANY PEOPLE MUST GET SICK IN BIG VACCINE TRIALS?

Some experts say that, ideally, 150 to 160 people in a trial of tens of thousands of participants must get sick before making a reliable assessment of a vaccine’s efficacy. That’s a bit of a rule of thumb, though, open to interpretation.

“There is no such regulatory standard requiring X number of events for making a reliable decision,” the government-funded Swiss Clinical Trial Organization said. “The amount of (infections) has to be seen in relation to the disease and its risk profile. It’s rather a case-by-case evaluation.”

Typically, regulators strive to have at least 95% certainty that the trial read-out is not the result of random variations with nothing to do with the tested compound.

For trial sponsors there is safety in numbers as a large enough trial can ensure that 95% reliability hurdle is cleared. But the larger the underlying clinical benefit, the fewer trial participants needed to create that clarity.

In Pfizer and BioNTech’s trial, they planned a final analysis when 164 people had become sick, with multiple, pre-planned interim analyses along the way. They skipped an analysis at 32 patients, and once they were ready to release a look at the 62-person mark, 94 had come down sick.

Details from the Russian trial are unclear, without access to its protocol.

HOW DO THESE RESULTS STACK UP TO OTHER DRUGS, OR VACCINES FOR OTHER ILLNESSES?

In normal drug trials, for diseases like terminal cancer, benefits of new medicines may be less apparent, with survival benefits of just a few months sometimes revolutionary for patients at death’s door.

For vaccines, however, marginal protection is inadequate, and the World Health Organization ideally wants to see at least 70% efficacy in trials, while the U.S. Food and Drug Administration wants at least 50%.

The 90% efficacy reported in the Pfizer and Russian trials beats those, and appears to exceed that of typical flu vaccines, which the U.S. Centers for Disease Control and Prevention (CDC) estimate reduce the risk of sickness by 40%-60%.

For other shots, the CDC estimates the efficacy of a two-shot measles vaccine at 97%, and a two-dose chicken pox vaccine at 90%. Two doses of polio vaccine are 90% effective, rising to nearly 100% with a third.

CAN WE EXPECT EFFICACY RATES TO HOLD UP AS TRIALS ADVANCE?

Pfizer acknowledged on Monday that its final vaccine efficacy percentage may vary. Still, Spiegelhalter said the study’s design seems likely to generally hold up, based on the 94 sick participants.

“In this case, the effect is so huge, even if there is a little bit of fallback – if the effects become slightly smaller over time – that is very unlikely to be significant.”

WHAT ABOUT REAL-WORLD EFFICACY, SHOULD THE VACCINES BE APPROVED?

The interim data is promising, since it appears to demonstrate that a vaccine can be effective in preventing COVID-19.

The jump to mass vaccinations, however, presents new hurdles, in particular for an mRNA vaccine like Pfizer and BioNTech’s that must be stored and shipped at minus 70 degrees Celsius (-94°F).

Moreover, the Pfizer-BioNTech vaccine requires two doses, ideally 21 days apart. If people do not stick to the timetable, it may affect the vaccine’s efficacy.

Protection against the mumps, for instance, drops from nearly 90% to 78%, if people don’t get a follow-up shot.

Swiss epidemiologist Marcel Tanner, president of Switzerland’s Academies of Arts and Sciences and one of the government’s top COVID-19 science advisers, expects possible variations in efficacy among older people, whose immune systems wane with time, or those with immune disorders.

“Efficacy says, ‘Does it work?’ Effectiveness says, ‘Can it be applied? Can you carry the efficacy to the people?'” Tanner said. “But no question: 90% efficacy, at that stage, is a pretty good result.”

(Reporting by John Miller in Zurich, Kate Kelland in London, Ankur Banerjee in Bengaluru, Julie Steenhuysen in Chicago and Polina Ivanova in Moscow; Editing by Josephine Mason and Nick Macfie)

Pfizer CEO made $5.6 million stock sale on same day as COVID-19 vaccine update: filing

(Reuters) – Pfizer Inc Chief Executive Officer Albert Bourla sold $5.56 million worth of company shares on Monday, the day the drugmaker said its COVID-19 vaccine was 90% effective based on interim trial results, a regulatory filing showed.

Bourla authorized the sale of the shares on Aug. 19, provided the stock was at least at a certain price, as part of a predetermined plan, the company said.

Bourla sold 132,508 shares at $41.94 per share, according to a Securities and Exchange Commission filing late Tuesday.

“The sale of these shares is part of Dr. Bourla’s personal financial planning and a pre-established (10b5-1) plan, which allows, under SEC rules, major shareholders and insiders of exchange-listed corporations to trade a predetermined number of shares at a predetermined time,” Pfizer said.

Pfizer said on Monday its experimental COVID-19 vaccine was more than 90% effective based on initial trial results, sending its shares higher along with the broader markets.

The company’s shares rose as much as 15% to trade at session high of $41.99 on Monday, before closing up 7.7%. They were trading at 38.75 on Wednesday.

Pfizer and German partner BioNTech SE have said no serious safety concerns were found so far and expect to seek U.S. emergency use authorization this month, raising the chance of a regulatory decision as soon as December.

(Reporting by Manojna Maddipatla in Bengaluru; Editing by Shinjini Ganguli and Shounak Dasgupta)