FDA

Why the Hearing Aid Rule is a Big Deal

by Matt Gontarchick

On August 16, the Food and Drug Administration (FDA) finalized rulemaking to allow hearing aids to be purchased over-the-counter (OTC), which is widely expected to increase access for millions of Americans with mild to moderate hearing loss.  This rule was 5 years in the making – why now? 

Background 

While FDA has regulated hearing aids for decades, the agency had previously only focused on assuring safety and effectiveness of prescription hearing aids.  In 2017, Congress stepped in and passed a law to require the agency to issue rules for over-the-counter devices. Lawmakers were hoping establishing a new category of hearing aids would address: 

  • Cost:  Lack of competition in the market means hearing aids can cost between $2,000 and $7,000 per pair.   
  • Coverage:  Most commercial insurance plans and Medicare don’t cover the cost of hearing aids for people with mild to moderate hearing loss because they’re not considered an essential medical device – or in other words, they’re considered “elective.”  
  • Access:  Additionally, getting hearing aids requires a prescription from an audiologist or other specialist.  Buying devices in a retail setting or online would provide more options for consumers. 

A Rule that Was Years in the Making 

It’s taken a long time for the idea of over-the-counter hearing aid sales to go from initial concept to final rule.  Sens. Chuck Grassley (R-IA) and Elizabeth Warren (D-MA) got so fed up with the agency dragging its feet that they introduced legislation to require FDA to issue rulemaking on OTC hearing aids.  Even though the bill was signed into law as part of the FDA Reauthorization Act of 2017, it still took the agency 5 years to finalize the rule.  Why?   

COVID.  Yes, the needed change in focus of the agency to address COVID was a no-brainer, but President Trump signed the bill 2+ years before the virus struck….   

Change in administration.  Yes there was a change in administration but it took President Biden until July 2021 to issue an executive order directing his own agency to issue rule making. 

So why the delay?  It turns out that balancing stakeholder concerns was complicated.  When FDA issued the proposed rule in October 2021, the agency received more than 1,000 comments from the public.  Here is where the rule ended up: 

  • Output levels:  Lowers the maximum sound output to reduce the risk from over-amplification of sound 
  • Volume control:  Requires all OTC aids have a user-adjustable volume control 
  • Label and packaging language:  Simplifies phrasing so safety concerns can be easily understood 
  • State authority:  Retains authority by States to require an audiological evaluation for minors and other previously granted State exemptions applicable to non-OTC hearing aids 

What’s Next?  

The final rule goes into effect in 60 days, which is the date that over-the-counter hearing aids can officially be marketed.  Already, Best Buy has announced that it plans to have hearing aids available in 300 of its 1,000 stores by the fall.   

Even though Congressional Democrats weren’t able to get Medicare coverage for hearing aids signed into law, the rule signals real financial relief and a step toward health equity for millions.  Good news for consumers makes for good politics…right ahead of the November 8th elections. 

FDA

It Is Time to Separate Food Safety from the FDA?

by Matt Gontarchick

Between the baby formula debacle and longer-than-expected review periods for COVID-19 vaccines, it’s been a rough year for the Food and Drug Administration (FDA).  The extent of the FDA’s problems is reflective of all the different responsibilities the vast agency has, ranging from control and supervision of food safety and tobacco products to pharmaceutical drugs and medical devices.  With the FDA’s plate so full, some policymakers feel splitting off food safety into its own agency is the best way forward.

The latest proposal to split up the FDA is the Food Safety Administration Act.  Introduced by Sen. Dick Durbin (D-IL) and Rep. Rose DeLauro (D-CT), the bill would spin-off the FDA’s food-related responsibilities into a separate Food Safety Administration.  DeLauro has referred to food safety as a “second-class citizen” at the FDA, and both she and Durbin have said creating a separate agency led by a Senate-confirmed food expert would lead to better outcomes for consumers.

They argue that establishing a separate Food Safety Administration would improve food safety and benefit consumers by applying “focused leadership” from a food safety expert capable of providing more accountability.  Additionally, the newly formed agency’s unified structure and direct oversight capabilities would ensure constant attention to food safety issues and more bandwidth to stay on top of foodborne illnesses.  

Indeed, policymakers have been discussing the separation of food safety from other FDA-regulated industries for years, or at least instituting reforms that would bolster the agency’s food safety responsibilities.  Here are some key examples from the past 15 years.

  • Some critics called for the FDA to be split into two agencies – one that handles drugs/medical devices and another than handles food safety and cosmetics – in the wake of a salmonella outbreak in 2008.
  • Other approaches have attempted to provide more resources and authorities for the FDA’s food safety arm as a way to bring about change from within.  In 2011, Congress enacted new measures that provided new regulatory programs for food importers, foreign producers, and fresh produce growers. 
  • In 2010, the Obama administration established the new position of a deputy commissioner for foods and veterinary medicine to provide direct oversight on food issues.  However, the Trump administration later took away the deputy commissioner’s authority over the agency’s respective policymaking units on food and veterinary medicine.  Notably, neither administration gave the deputy commissioner oversight authority on the agency’s food inspection and import activities.
  • In June 2018, the Trump administration proposed a plan to consolidate the FDA’s food safety functions into a new agency within the US Department of Agriculture (USDA) known as the Federal Food Safety Agency.  The FDA would have been renamed the Federal Drug Administration, but Congress would not extend him the power to reorganize the government. This similarly happened during the Obama administration where the administration put together a similar proposal to fold the FDA’s food inspection and enforcement services into the USDA Food Safety and Inspection Service in 2015.

The FDA is also focusing on ways to improve.  Scrutiny over the agency’s regulation of electronic cigarettes and baby formula prompted the agency to order an external review of its activities on tobacco regulation and food safety.  The review will focus on the agency’s Human Foods Program, which Commissioner Robert Califf said has been stressed from the COVID-19 pandemic. 

The Reagan-Udall Foundation, which has been tasked with reviewing the agency, is set to complete its report by the end of September.  While it remains to be seen what the foundation will recommend, breaking up the agency into a separate entity focused on food might be the best move for consumers.  Former Deputy Commissioner for Food Michael Taylor recently wrote that food has been a “low priority” at the agency for decades.  One reason for this is the fact that most FDA commissioners are physicians whose expertise pertains to drugs, meaning they have little time or bandwidth set aside for food. 

Another reason for FDA’s second-class status is a lack of sufficient funding.  Over the past 10 years, FDA’s food funding has grown by 42%, while funding for the agency’s drug and device-related programs has increased 122%.  

But does the FDA even have to wait for Congress to split it up?   As Taylor argued, the FDA commissioner and the secretary of health and human services (HHS) could use their own authority to unite all the FDA’s food offices under a single deputy commissioner with strong oversight powers.  But until any serious reforms are made, the agency will likely struggle to find a way to give the proper time and attention to its long list of priorities.

Congress

FDA User Fee Process: The Clock Is Ticking

by Matt Gontarchick

September 30, 2022.  That’s the date the Food and Drug Administration’s (FDA) user fee programs for drug products and medical devices are set to expire.  Given the “must-pass” nature of user fee reauthorization, lawmakers and FDA stakeholders are using this moment to advance other FDA-related reforms pertaining to the accelerated approval process, promoting clinical trial diversity, competition in drug markets, and other areas.  While the House and Senate user fee packages are fundamentally similar, there are some differences between the two.  For instance, the Senate package includes policies related to dietary supplements, diagnostic labs, and cosmetics; the House does not.  Given the differences between the packages and the pressure to get a signed bill before the August recess, stakeholders would be keen to watch the legislative process unfold.

A Brief History of the FDA User Fee Process

Enacted in 1992, the Prescription Drug User Fee Act (PDUFA) authorized the FDA to collect user fees from companies that submit applications for drug products.  Since then, Congress has added additional user fee programs for other products like medical devices, generic drugs, and biosimilars.  Congress reauthorizes user fee bills every five years, and the reauthorization process marks an important opportunity for lawmakers to consider FDA-related policies as well as overall FDA performance. 

Since FDA depends on user fees to operate, failure to reauthorize user fee programs would catastrophically disrupt FDA operations by triggering massive layoffs of career staff who review new drugs and devices and monitor drug safety.   As a result, the timelines for new drug products to reach patients and providers would increase exponentially.   

Although current authority for the user fee programs expires at the end of Fiscal Year (FY) 2022, Congress typically passes reauthorization bills in the summer preceding the September deadline to avoid disrupting FDA operations. With that in mind, the House and Senate are on the clock to pass a legislative package over the next couple of months before the FDA starts handing out pink slips.

What’s in the House and Senate Bills?

The House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions (HELP) Committee have already released their own respective user fee reauthorization bills that would reauthorize fees that drugs, biosimilars, and medical device companies must pay the agency for review of their products.  Both bills appear to move forward with fee levels that were negotiated between FDA and industry groups prior to their release. 

Additionally, both bills set out to reform the FDA’s accelerated approval program, which allow the agency to approve drugs more quickly for serious conditions that fill an unmet medical need.  In exchange, drug manufacturers must complete post-approval trials to confirm those clinical benefits – something the FDA has not consistently ensured. 

Both the House and Senate bills would allow the FDA to require manufacturers to start post-approval studies prior to accelerated approvals, give the FDA more control over study design and deadlines, and create a mechanism for the agency to pull drugs off the market.  The bills also would clarify that post-approval studies could rely on real-world evidence (RWE) to confirm that drugs are effective.  Notably, the Senate bill differs from the House bill in that it would create an interagency coordinating council that would periodically review accelerated approvals.

Additionally, both bills set out to promote drug competition through better access to generic and biosimilar drugs, albeit through different paths.  For instance, the House bill contains provisions that would streamline the generic approval process in certain types of cases, while the Senate bill addresses exclusivity for interchangeable biosimilar products.

Outside of fee proposals, changes to the accelerated approval process, and access to generic and biosimilar drugs, both bills contain several notable differences.  For example, the House bill includes provisions aimed at improving diversity in clinical trials by requiring trial sponsors to submit diversity action plans with details on how the sponsors intend to enroll a diverse group of trial participants.  Other provisions would require the FDA to submit reports on diversity action plans and to hold public workshops on improving trial diversity. While the Senate bill does not contain such a provision, another Senate HELP Committee-approved bipartisan bill, the PREVENT Pandemics Act, does include policy intended to promote clinical trial diversity.

Among the Senate’s user fee package proposals are provisions that would enhance the regulation of laboratory-developed tests (LDTs) by allowing the FDA to regulate LDTs based on the level of risk associated with them, similar to how the agency regulates medical devices.  The Senate bill would also expand the FDA’s ability to regulate dietary products by requiring dietary supplement companies to list their products with the agency, which would theoretically improve the FDA’s ability to enforce consumer protections.  Furthermore, the Senate bill contains a slew of provisions aimed at boosting regulation of cosmetics.  These include requirements for cosmetics manufacturers to register their products with the FDA, new labeling requirements, and the establishment of good manufacturing practice regulations.

What Comes Next?

The House Energy and Commerce Committee voted in favor of its user fee package in the Health Subcommittee on May 11 and the full committee on May 18 with a vote on the House floor scheduled for June 7.   Over in the Senate, the HELP Committee is scheduled to mark up its user fee package on June 14, along with legislation to improve access to mobile health clinics. 

Congress has always addressed the user fee reauthorization legislation ahead of the expiration deadline (September 30), and leaders from both House and Senate committees with jurisdiction over the FDA have publicly stated that they don’t want to hold up the reauthorization process.  However, substantive differences between the House and Senate versions of the reauthorization bill combined with a highly partisan climate have the potential make passing user fee legislation more difficult than in previous years. 

Additionally, the Senate HELP Committee has also voted in favor of its PREVENT Pandemics Act, another top priority of Chair Patty Murray (D-WA) and Ranking Member Richard Burr (R-NC), who is retiring at the end of this year, for enactment.  Likewise, a priority of House Energy and Commerce Health Subcommittee Chair Anna Eshoo (D-CA) will be enactment of her bipartisan House legislation creating the Advanced Research Project Agency for Health (ARPA-H).  It remains unclear if/how these policy priorities and user fee reauthorization packages will come together and form one bill to be signed by the President before the expiration of the current user fee programs. As the summer unfolds, stakeholders would keen to monitor the reconciliation process to see which provisions and changes make it into the final reauthorization bill.

FDA

Is Public Pressure Impacting the FDA’s Vaccine Review Strategy?

by Matt Gontarchick

Parents of young children are frustrated and mad.  While adults have been able to get third and even fourth COVID-19 vaccines doses for some time now, children under six years are still unable to get their shots while the rest of society reverts to a pre-pandemic normal.

Anger among parents hit a boiling point last week when White House Chief Medical Advisor Dr. Anthony Fauci confirmed reports that the Food and Drug Administration (FDA) will not approve vaccines for kids under 6 until it can simultaneously review and approve vaccines from both Pfizer and Moderna.

However, less than a week later, FDA officials seemingly changed course when they announced that they may move forward on reviewing Moderna’s vaccine without waiting for Pfizer’s application – meaning that young children could get vaccinated as soon as June.  What caused the FDA to take an about face on its vaccine review strategy?

At the time of Fauci’s comment on April 21, Moderna was poised to begin applying for an emergency use authorization (EUA) within the next week or two, as initial data showed its vaccine generated strong protection in kids.  News that the FDA could soon begin reviewing Moderna’s EUA application set off a sign of relief among parents, who have had to contend with constant delays in the race to get young kids vaccinated.

However, Pfizer’s vaccine for children under 5 is still undergoing clinical trials for a three-dose regimen after results from a two-dose regimen did not yet provide strong protection against the virus, and it’s not clear when Pfizer will be ready to submit its data.  By waiting to review vaccines from both companies, the timeline for getting shots into kids’ arms faced a decent chance of getting extended once again.

What was the FDA thinking?  According to reports,  FDA officials wanted to review vaccines from Moderna and Pfizer simultaneously because approving both at the same time would be less confusing for parents than approving each at different times.  Additionally, FDA officials were worried about a possible backlash from parents if the agency approved Moderna’s vaccine first and Pfizer’s several week later when Pfizer’s vaccine demonstrated stronger efficacy. 

Despite the FDA’s rationale, reports that federal officials were delaying the review process once again elicited a strong backlash from concerned parents and lawmakers.  In the days following Fauci’s comments, lawmakers wrote to the FDA requesting an explanation as to why vaccines for young children were being delayed again, and parents and pediatricians launched an advocacy campaign to urge the FDA to review each vaccine application “at the earliest opportunity.”

Did Public Pressure Make a Difference?

The FDA finally changed its tune on April 29, when a top official announced the agency will consider vaccine applications as soon as they are ready.  While it is not clear if the FDA shifted its strategy purely in response to political and public pressures, it wouldn’t be first time public pressure might have made a difference. 

In mid-2021, the FDA appeared to be on track to approve the vaccine for children aged 5-11 by early fall, just in time for the start of school.  However, in July, the FDA asked Pfizer and Moderna to expand the size of their clinical trials for children to make sure they could detect potentially rare side effects, namely myocarditis, or heart inflammation – effectively pushing the timeline for vaccine approval out to winter 2021 or early 2022.  This drew sharp criticism from parents and pediatricians, who argued that complications from COVID-19 posed a greater threat to kids than myocarditis.

The strongest sign of pressure on the FDA came in the form of an August 2021 letter from the American Academy of Pediatrics (AAP) that called on agency to stick to its original timeline for collecting data and authorize vaccines for children under 12 as soon as possible.  A month after the pediatricians weighed in, the FDA issued an unprecedented statement saying that it would no longer wait for additional follow-up data from expanded clinical trials to made a decision on an EUA and stick to its original timeline. 

Like many things with the pandemic, nothing is certain as the FDA determines how it will review vaccines for younger children.  Moderna only began to submit data for its EUA on April 28, and the FDA has laid out a tentative schedule that leaves open the possibility that kids under 6 could get their shots sometimes this June.  However, things could still change. An FDA official say the agency could still review EUA applications from Moderna and Pfizer simultaneously if both are filed less than a week apart, and many parents and pediatricians say June is still too long of a wait for young kids to get vaccinated, especially considering that the review process for other age groups took less time. 

However, actions undertaken by the FDA last fall and last week suggest that the agency isn’t immune to public pressure.  This sets up a precedent where advocacy could sway the FDA review process in the future – for better or for worse.

FDA

Will We Need More Booster Shots?

by Matt Gontarchick

People will only need annual COVID-19 booster shots after getting their third vaccine dose, according to a top Food and Drug Administration (FDA) official at the 2022 Innovation in Regulatory Science Summit in January 2022.  Since then, however, mounting evidence over waning immunity plus the potential of a new wave of COVID-19 are feeding calls for people to get their fourth vaccine doses sooner rather than later.  Does that mean Americans can expect to get a second booster shot in the coming months?

First, some Americans are already able to get a second booster shot.  According to guidance from the Centers for Disease Control and Prevention (CDC), people ages 12 years and older who are moderately or severely immunocompromised should receive a total of four mRNA vaccine doses.  This includes transplant patients and those undergoing chemotherapy for cancer.

Drug manufacturers are already asking for approval on second boosters for additional populations.  In mid-March, Pfizer and Moderna submitted applications to the FDA for an emergency use authorization (EUA) for a second booster dose of their respective COVID-19 vaccines.  While Pfizer is specifically seeking an EUA for adults over age 65, Moderna is requesting an EUA for anyone over 18 years of age. 

The submission of both applications came just days after Pfizer CEO Albert Bourla said a fourth vaccine dose will probably be needed for everyone.

  • One reason for this is mounting data that shows protection acquired from a third COVID-19 vaccine dose wanes over time.  According to CDC data, a booster shot’s effectiveness in protecting against hospitalization dropped from 91% to 78% between August 2021 and January 2022 – a timeframe that includes both the Delta and Omicron variants. 
  • Another reason for a fourth shot is a need to protect Americans ahead of a new wave of COVID-19 cases.  In recent weeks, a new Omicron subvariant known as BA.2 has driven an increase in cases across Europe, which many experts say could foreshadow an increase in cases in the US within the coming weeks.  Although BA.2 is roughly 30% more transmissible than the original Omicron strain, it does not appear to be more severe or lead to more hospitalizations.  While overall COVID-19 case numbers are still trending downward in the US, 10 states have reported an increase in case numbers over the last 14 days. 

Due to these concerns over waning immunity and growing case numbers, nearly a dozen countries including Australia, Belgium, Denmark, Israel, Poland, Sweden, and the United Kingdom have already begun offering fourth doses, albeit eligibility is limited to seniors and medically vulnerable people in most cases.  Additionally, reports suggest the FDA could authorize second boosters for all adults over age 50 as soon as March 29.  However, that doesn’t necessarily mean the government will follow suit in recommending a fourth mRNA vaccine dose to every individual age 12 and up who’s already cleared to get a third dose anytime soon, as a couple issues stand in the way.  These include:   

  • Regulatory approval.  The FDA’s vaccine advisory committee will meet on April 6 to discuss the need for additional COVID-19 booster shots.  However, the advisory panel will NOT be reviewing any EUA applications from Pfizer or Moderna or taking a vote on recommendations – instead, the committee will discuss the timing and populations for additional doses in the coming months.  The April 6 agenda is a sign of the federal government’s cautious approach to boosters, which means it might take some time for federal regulators to sign off on additional doses, especially for the broader population.  In September 2021, for instance, a CDC advisory panel declined to recommend third doses for people who work in “high-risk” settings like health care practitioners and teachers – a decision which was ultimately overruled by CDC Director Rochelle Walensky.
  • Data.  Even though a number of countries have already cleared fourth shots for certain populations, the jury’s still out on whether a second booster will make a difference for non-elderly adults who are not considered medically vulnerable.  Preliminary results from a study involving 154 health care workers in Israel found that a fourth mRNA dose is only “partially effective” in protecting against the Omicron variant.  Without any strong evidence of the effectiveness of a fourth shot, US regulators are likely to continue to take a cautious approach on recommending additional boosters for the broader population.
  • Funding.  Lawmakers dropped $15 billion in additional COVID-19 funding from the Fiscal Year (FY) 2022 omnibus appropriations bill, and so far, congressional leaders are locked in a stalemate on passing separate legislation on additional COVID-19 support.  Without additional funding, Biden administration officials have warned that they won’t have enough money to purchase a potential fourth vaccine dose for even 70% of all Americans.  And barring additional funding, the federal government will no longer be able to cover the cost of vaccinations for uninsured people starting on April 5, which means uninsured immunocompromised Americans may not be able to afford a booster if they need one.

Ultimately, the trajectory of the COVID-19 pandemic may ultimately inform whether additional boosters are necessary for Americans, and in turn, whether Congress decides to allocate enough money to pay for additional vaccine doses.  While White House Chief Medical Advisor Anthony Fauci has acknowledged that the BA.2 subvariant is likely to cause cases to rise in the US, he doesn’t anticipate new cases will culminate in a major surge that results in high levels of hospitalizations. 

Indeed, a good portion of the US population has acquired some degree of immunity through infection, vaccination, or both over the last two years of the pandemic, which could protect Americas from the worst consequences if case numbers continue to rise over the next few weeks.  However, if hospitalizations suddenly spike across multiple populations, it may be too late for the federal government to act swiftly on additional boosters.

FDA

What Would the End of the Public Health Emergency Mean for EUAs?

by Matt Gontarchick

The current public health emergency (PHE) is set to expire on April 16.  While the Biden administration is likely to extend the PHE, administration officials have yet to comment on their specific plans.  Uncertainty over the end of the PHE has fueled conversations over what the implications would look like for temporary health care policies that expire once the PHE officially concludes. 

Blog posts from the last two weeks have looked at how the end of the PHE would affect Medicare’s temporary telehealth waivers and Medicaid coverage.  This week’s blog post focuses on how ending the PHE would impact the Food and Drug Administration’s (FDA) emergency use authorizations (EUAs).

Background:  An EUA allows the FDA to authorize unapproved medical products or unapproved uses of approved medical products – like vaccines and treatments – to be used to diagnose, treat, or prevent serious or life-threatening diseases in cases where there are no adequate, approved, and available alternatives.  Since the start of the COVID-19 PHE on January 31, 2020, the FDA issued hundreds of EUAs for pharmaceutical and medical devices related to COVID-19.

How? Section 564 of the Federal Food, Drug and Cosmetic (FD&C) Act allows the FDA to issue four different types of EUAs during a PHE for diagnostics, respiratory equipment, medical devices, and drugs/biologics.  However, the FDA still has the authority to issue an EUA outside of a PHE thanks to the Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) of 2013, which grants Department of Health and Human Services flexibility to declare that “circumstances exist” outside of a PHE to allow EUAs to be issued.

What does the end of the PHE mean for the EUAs?  Unlike the other temporary authorities related to telehealth and Medicaid, all EUAs that are issued by the FDA remain in effect until the FDA withdraws the EUA declaration.  For instance, the EUA declarations issued for the Zika and Ebola pandemics were never withdrawn and are currently in effect, even though their respective PHEs have long since expired. 

However, one FDA policy, separate from EUAs, will expire at the conclusion of the PHE – enforcement discretion.  This policy allows the FDA to waive enforcement of its usual requirements for pre-market approval to allow drug products to be modified for additional uses without full approval from the agency.  In contrast, drug products approved via an EUA must still meet specific criteria on safety and effectiveness.  Once the PHE ends, the FDA will revert to its regular enforcement policies, and all products where enforcement discretion once applied must then meet all standard FDA legal requirements in order to continue to be sold in the US.  

Planning for a Post-EUA Future

Unlike the EUAs for Zika and Ebola treatments, the FDA has communicated that it doesn’t want the COVID-19 EUAs to stick around forever and manufacturers should expect an “eventual resumption of normal operations.”  To this end, the FDA issued two draft guidance documents in late December to help facilitate a return to normal:

Uncertain Future for Stakeholders

On February 22, the FDA held a webinar for industry stakeholders about its draft guidance documents on its post-pandemic transition plans, and like their counterparts in telehealth and Medicaid, the stakeholders from the pharmaceutical and medical device industries had a lot of questions. 

  • Of the four EUA declarations, three are specific to devices, and it’s not clear if the agency will withdraw those EUAs all at once or at different times.
  • The webinar did not offer stakeholders a clear answer on whether HHS issues the advance notice on withdrawing the EUA declarations first, or FDA will finalize its two guidance documents on its transition plans.   Instead, FDA staff told attendees that whatever happens first depends on the course of the pandemic.  If hospitalizations continue to decline and stay low, HHS may pull the EUA declarations first; otherwise, finalization of the guidance documents could come sooner.
  • The FDA says more guidance is on the way, but it’s unknown when it will be released.  According to FDA staff, this would pertain to the types of data FDA will consider when transitioning a drug product from an EUA to formal market access, such as how real-world evidence will be considered. 

While pharmaceutical industry stakeholders can feel relieved that EUAs won’t expire with the end of the PHE and that the FDA is making plans for a post-pandemic world, question about what that world will look like simply add to the narrative that the federal government’s take on health care policies once the PHE ends need significant refinement.

FDA

When Can Kids Under 5 Get Vaccinated?

by Matt Gontarchick

An average 672 children per day last week were admitted to the hospital with COVID-19 last week, the highest number since the COVID-19 public health emergency began.  Surging case numbers are also causing schools to close and temporarily revert to virtual learning.  While children ages 5-17 can be vaccinated for protection against COVID-19, this currently isn’t an option for children under 5 years of age.  Even though pharmaceutical companies have been working on vaccines for younger children, some bumps in the road means the timeline for getting this cohort vaccinated hasn’t exactly been static.

Pfizer’s Swing and a Miss

Pfizer was the first COVID-19 vaccine developer to begin testing vaccine in children under five.  For its late-stage clinical trial, Pfizer administered two 3-microgram doses three weeks apart, which is less than one-third of the dose given to older children. 

Pfizer initially hoped to submit data on the efficacy of its vaccine in children in the first quarter of 2022, but an announcement from the company on December 17, 2021 signaled a delay in the timeline young children can get vaccinated.  According to Pfizer, its 3-microgram dose yielded high level of protection in children ages 6- to 24-months-old but did not generate a sufficient level of protection in children ages 2 to 5. 

Now, Pfizer is amending its clinical trial to add a third 3-microgram dose for children 6 months to 5 years of age.  If the updated trials are successful, Pfizer says it will submit data to the Food and Drug Administration (FDA) in April, which pushes the timeline for young children to get the company’s vaccine back by a few months. 

What about Moderna?

News that Pfizer is extending its trial left parents of younger kids understandably upset.  Fortunately, Pfizer is not the only company developing vaccines for children.  Moderna is currently conducting trials in children ages 6-months to 5-years-old, and the company expects to have results available by the end of January, which means the FDA could provide emergency approval as soon as late February or early March 2022.  Moderna is also testing younger children with a higher-microgram dosage than Pfizer, which presumably increases the likelihood that Moderna’s vaccine will yield an adequate immune response.

Children’s Risk Still Very Low

Even though it will probably be a few more months until younger children can get their shot, parents should feel some assurance that young children’s risk of complications from COVID-19 is extremely low.  The COVID-19 death rate for children ages 0-17 in the US is 0.1%, by far the lowest for any age group (in comparison, the death rate for US adults ages 50-64 is 1.39%). 

While pediatric hospitalizations related to COVID-19 are at a record-high, many of these hospitalizations are incidental, meaning children are being hospitalized with, but not for COVID.  An example of an incidental pediatric hospitalization could be for a child who falls on the playground, is admitted to the hospital for a broken bone, and only tests positive as a part of routine screening.

Additionally, young children who are infected with COVID-19 overwhelmingly exhibit mild symptoms or are asymptomatic, with hospital stays rare.  And while it is possible that young children can become COVID-19 long-haulers, studies are increasingly showing that long-COVID in kids is also rare. 

News of Pfizer’s clinical trial results was certainly disappointing for parents.  But with the possibility of better clinical trial results in the future plus strong data on the low level of risk for young children, parents should have a somewhat optimistic outlook heading into the third year of the pandemic.

Administration

Why Aren’t Rapid COVID-19 Tests More Readily Available in the US?

by Matt Gontarchick

“Should we just send one to every American?”  That’s what White House Press Secretary said on December 7 when asked during a press briefing why more Americans don’t have access to rapid antigen tests. Psaki’s response – which many deemed sarcastic – sparked a wave of backlash from members of the medical community who think that’s exactly what the Biden administration should do and make tests available to everyone at no cost.  So why isn’t the administration doing it?

Rapid tests are seen as an important public health tool for reducing the spread of COVID-19 because they can be used at home by an individual and provide results in as little as 15 minutes.  While not as accurate as PCR tests, rapid tests are available over- the-counter, which makes it easier and more convenient for people to get access tests.  And more people taking rapid tests would mean identifying more COVID-19 cases than would otherwise be possible with only PCR testing. Having an increase in access to rapid tests could also make forthcoming COVID-19 antiviral pills more useful, since their effectiveness depends on being taken within the first five days of illness.  Due to the convenience of rapid tests and their potential to stop the spread of COVID-19, some public health experts have pointed to over-the-counter tests as a way to potentially control the pandemic and return to “normal life.”

Currently, the availability of rapid tests in the US pales in comparison to other wealthy nations, where people can readily access tests at little or no cost.  In Germany, rapid tests are available in grocery stores for less than $1, while people in the United Kingdom can request mail-order rapid tests free-of-charge.

Here are some of the reasons why Americans can’t get rapid tests as easily as Germans or the British.

  • Regulatory issues.  Some manufacturers say the regulatory framework on rapid tests is too stringent because it requires test performance benchmarks to be at the same level of PCR tests, which test developers say is too high.  Additionally, US standards for approval are higher compared to some other peer nations, including the UK.
  • Supply chain problems.  There has been a consistent shortage of raw materials used to manufacture the diagnostic components of at-home tests.  Additionally, low COVID-19 case numbers during the summer caused some manufacturers like Abbott to pull-back on test production, leaving the company unable to keep up with increased demand for tests once case numbers began to jump in July 2021.
  • Lack of federal investment.  While the US government has invested billions of dollars into the development of vaccines, much less has been put towards the development and purchase of rapid tests.  In contrast, countries like the UK and Germany invested billions in both vaccines and at-home tests.   

Fortunately, rapid tests are a part of the Biden administration’s plans to combat COVID-19.  On December 2, President Joe Biden announced that insurance companies will soon reimburse individuals who buy over-the-counter rapid tests.  Other recent actions the administration has taken include investing $650 million to strengthen manufacturing capacity for rapid tests and a $70 million investment to develop an accelerated pathway within the Food and Drug Administration (FDA) to evaluate rapid tests.

But…rapid tests might not make a huge difference, anyway.  While rapid tests were frequently lauded by public health officials as a way to curb the pandemic, real-world evidence in countries where rapid tests are readily available suggests otherwise. In Germany, infections, hospitalizations, and deaths have increased dramatically since October, while the UK has seen COVID-19 case numbers grow since restrictions were fully lifted in July (although hospitalizations and deaths remain low). 

And even though Biden recently committed to new investments in testing, which could result in 300 million new rapid tests per month, it would still amount to less than one test per month per person in the US. 

While convenience of rapid tests is undeniable, a boost in the availability of tests might accomplish little in the US, where most of the country is already grappling with a surge of new cases.

FDA

Will COVID-19 Antiviral Pills Make a Difference?

by Matt Gontarchick

A new era in treating COVID-19 could be upon us. On November 30, the Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) will discuss Merck’s request for an emergency use authorization (EUA) for Molnupiravir, an  oral antiviral drug to treat COVID-19.  But Molnupiravir isn’t the only oral COVID-19 antiviral in the mix – in October 2021, Pfizer requested an EUA for Paxlovid, its antiviral pill.  If FDA advisors recommend an EUA for Molnupiravir, and eventually Paxlovid, could it change the course of the pandemic as we know it?

The FDA has already authorized a few treatments for COVID-19, but they have serious drawbacks.

  • Remdesivir the only treatment to have received full FDA approval, has limitations.  For example, it has to be administered intravenously (meaning it’s difficult to provide in an outpatient setting), it’s expensive (about $2,600 for a three-day regimen), and recent research says it’s not very effective.
  • Monoclonal antibodies, which have received an EUA from the FDA, offers another treatment option. While studies show monoclonal antibodies are effective at reducing hospitalization and death, they suffer from many of the same drawbacks as remdesivir – they still have to be provided intravenously, and they’re still expensive (about $2,000 per treatment).

Enter Molnupiravir and Paxlovid. Both antiviral drugs stop SARS-CoV-2, the virus that causes COVID-19, from replicating in the body, but do so in different ways.  Molnupiravir, which was first developed as a flu treatment, works by fooling the virus’s RNA into creating mutations that render the virus unable to survive.  Paxlovid takes a different approach by disrupting the virus’s replication by destroying enzymes vital to its reproduction.

Both treatments offer clear advantages compared to their predecessors. A prominent advantage is early intervention, which is key to administering antiviral treatments.

  • Severe COVID-19 has two stages – one where the virus initially infects a person, and another when the immune system overreacts and spirals out of control. Remdesivir is typically administered in the second phase, when a patient is already hospitalized – and the damage may already be done.
  • Molnupiravir and Paxlovid, on the other hand, attack the virus before it can wreak havoc and put people in the hospital, avoiding further stress on the health care system.  

Additionally, both antiviral pills can be administered orally, meaning patients can take them in any setting. And unlike intravenous treatments, Merck and Pfizer’s antiviral drugs are much easier to ship and store.

  • Oh, and about that name. Molnupiravir comes from Mjölnir, the mythical hammer of the Norse god Thor.

Plans for distribution of the antiviral pills are shaping up.  The Biden administration purchased 1.7 million courses of Molnupiravir for $1.2 billion back in June and is now considering options to buy 1.4 million more.  Based on this agreement, Molnupiravir will cost roughly  $700 per patient, a more than 50% reduction from currently approved treatments.

Additionally, the administration is planning to buy enough courses of Paxlovid for 10 million people.  To allow their drugs to be manufactured around the globe and sold at lower prices in poorer countries, both Merck and Pfizer have entered into license-sharing agreements.

However, Molnupirabir and Paxlovid aren’t magic bullets, and while they are far better than currently approved treatment options, they still have limitations of their own.

  • First, both have a strict dosing regimen.  Each must be taken over a five-day period, with Molnupiravir taken four times a day and Paxlovid taken three times a day. 
  • Second, both antivirals must be taken within the first five days of illness.  Unfortunately, a lack of access to both rapid at-home antigen tests and testing labs that can quickly process PCR results means the onset of symptoms, a positive test result, and a prescription for an oral antiviral may exceed the five-day window.
  • Third, there are questions about the efficacy of the oral antivirals.  Merck originally reported in October 2020 that Molnupiravir reduces risk of hospitalization or death by 50%.  However, in November, updated data from Merck revealed that its antiviral only cut the risk of hospitalization and death by 30%.  Pfizer says that Paxlovid reduces the risk of hospitalization and death by 89%, but these results have yet to be peer-reviewed.

Despite these limitations, both Molnupiravir and Paxlovid could be the most important pharmaceutical development since the introduction of vaccines. However, just like vaccines won’t make a difference until people get their shots, new antiviral pills won’t help unless people take them. If the administration wants to ensure oral antivirals are utilized effectively , it needs to drastically improve the testing infrastructure and ensure adequate distribution to suppliers. Doing so will ensure as many people as necessary have access to antivirals and allow the new drugs to be an effective additional tool to fight the pandemic.  

Administration

What’s Going on with Booster Shots?

by Matt Gontarchick

There’s been a lot of discussion about COVID-19 booster shots lately – so much so, that it’s hard to keep track of who can get booster shots and what kind of booster shots are available.  Here, we provide a lay of the land on booster shots.

Why are booster shots necessary?  Booster shots provide an extra “boost” to immunity through an additional dose that cues the immune system to produce a stronger antibody response.  While all three currently approved vaccines from Pfizer, Moderna, and Johnson & Johnson are highly effective in protecting against hospitalization and death, a growing number of studies show that vaccine efficacy gradually wanes over time. 

Who can get booster shots now?  Pfizer’s COVID-19 vaccine is the only vaccine that is currently authorized by the Food and Drug Administration (FDA) to be used as a booster dose.  The FDA formally amended the emergency authorization use (EUA) for the Pfizer vaccine on September 22.  According to the amended EUA, the following people are eligible for booster shots at least six months after their initial series of shots:

  • People over age 65.
  • People ages 18 to 64 at high risk of severe COVID-19 due to chronic medical conditions or compromised immune systems.
  • People with greater risk of workplace exposure, such as frontline medical workers, teachers, and emergency responders.

More booster shots are on the way.  The FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted during an October 14-15 public meeting to recommend booster doses from Moderna and Johnson & Johnson. The panel recommended the Moderna booster be administered under the same criteria as Pfizer’s – six months after the second dose for people over 65, individuals at risk for serious complication from COVID-19, and essential workers.  However, the panel recommended broader criteria for the Johnson & Johnson booster – it said anyone who received the single dose Johnson & Johnson vaccine should be eligible to receive a second booster dose at least two months later. 

  • Why? Several studies have shown the Johnson & Johnson vaccine is less effective that other currently approved shots, particularly against new variants like Delta.

What happens next: The CDC Advisory Committee on Immunization Practices (ACIP) will meet on October 20-21 to offer its recommendations on who should get the Moderna and Johnson & Johnson booster shots.  Its recommendations are subject to a final decision from the CDC director.  Afterwards, the FDA could officially authorize booster shots from both companies in the following days. 

The conversation on booster shots hasn’t been without controversy.  Over the past few months, scientists, researchers, and public health officials within the federal government haven’t seen eye-to-eye on when booster shots should become available, and who should get them. 

  • For example, CDC Director Rochelle Walensky partially overruled ACIP last month when the panel initially declined to offer booster shots for essential workers under 65 who do not have chronic medical conditions.  Some ACIP members said that without additional data, they weren’t comfortable automatically allowing younger people to get boosters just because of their jobs.  While Walensky acknowledged the panel’s uncertainty, she said in a statement that CDC must use “imperfect data” to “take actions that we anticipate will do the greatest good.”
  • There are also ethical considerations as billions worldwide remain unvaccinated.  While many public health experts believe people with chronic health conditions should get additional shots, they feel extra doses should be allocated to countries with low vaccination rates first in order to prevent more dangerous variants from developing. 

The administration’s internal disputes have been quite apparent to the public.  Back in August, President Biden announced a plan to start distributing booster shots to all eligible Americans as soon as September 20.  However, the health care agencies tasked with rolling out boosters have taken a more conservative approach, and one month later after Biden’s original deadline, only certain segments of the population have access to one vaccine booster.   

With limited information and uncertainty about the future of the virus, administration officials are between a rock and a hard place.  On one hand, federal officials don’t have enough data to make definitive decisions on who needs a booster and how much a booster would improve efficacy.  On the other hand, the administration knows it can’t wait for definitive findings to become available, especially if case number surge once again in the next few months as colder temperatures drive more Americans indoors.

At the end of the day, COVID-19 is still a novel virus, and there are many unanswered questions on how long protection from vaccines last and how much that protection varies between different groups of people.  While new data on vaccines will continue to gradually become available, federal health officials will have to continue discussing and weighing the risks and benefits of authorizing vaccines in the US.   

FDA

When Are Kids Going to Get Vaccinated?

by Matt Gontarchick

Parents are mad.  While grown-ups have been eligible for COVID-19 vaccines for almost a year, there currently aren’t any options for children under 12.  This is especially concerning for many parents as the kids return to school amid a nationwide surge in cases.

A Different Process

On September 20, Pfizer/BioNTech released data showing its mRNA vaccine is safe and effective in children aged 5-11.  As the Food and Drug Administration (FDA) has fully approved the vaccine for individuals aged 16 and older and Pfizer/BioNTech vaccine is still available to individuals aged 12 to 15 through emergency authorization, why is the approval process taking so long for children?   

  • More data.  Earlier this year, FDA asked Pfizer/BioNTech and the other vaccine developers to provide six months of follow-up data for all clinical trial participants.  In comparison, the approval process for adults only required two months of follow-up data. 
  • More scrutiny.  Unlike the emergency use authorization (EUA) for adults, FDA doesn’t just rely on a company’s summary of the clinical trial data for children’s vaccines.  The agency looks at individual reports from every child, including data on side effects and blood tests. 
  • Biological differences.  Kids aren’t simply smaller adults.  Children have more active immune systems than grown-ups, which means scientists need to ensure they’re providing the right dosage.  Pfizer/BioNTech has specifically been testing children aged 5-11 with a two-dose regimen administered three weeks apart.  Each dose contains 10 micrograms, which is about a third of the dosage used for individuals aged 12 and up.

Pressure Grows for FDA to Speed Up Timeline

Earlier this year, it appeared that FDA would be able to approve vaccines for children aged 5-11 by early fall, just in time for the start of school.  However, signs that the approval timeline would extend first appeared in July when FDA asked Pfizer and Moderna to expand the size of their clinical trials for children to make sure they could detect potentially rare side effects, namely myocarditis, or heart inflammation.  These changes caused many health experts to revise their predictions on a timeline for approval for EUA, with some saying that the FDA would not make a decision until winter 2021 or early 2022.

The prospects of a longer timeline combined with a nationwide surge in cases sparked panic among many parents of younger children.  While COVID-19 poses a low risk for healthy kids, there is a justifiable concern about immunocompromised children as well as the ability for kids to pass the virus onto vulnerable adults.  As a result, some parents are even looking for doctors to skirt the rules and vaccinate their children, while others are signing their kids up for clinical trials, even though it’s unknown whether their child will be receiving the vaccine or a placebo.

Pressure from Pediatricians: The American Academy of Pediatrics (AAP) urged the FDA in an August 5  letter to “continue working aggressively towards authorizing safe and effective COVID-19 vaccines for children under age 12 as soon as possible” due to the threat posed by the Delta variant.  Specifically, AAP indicated that a two-month follow-up period to collect safety data is sufficient, as opposed to the six-month period FDA initially requested.  AAP also noted that reported cases of myocarditis in children who are receive mRNA vaccines like Pfizer/BioNtech’s are “extremely rare.”

The FDA is listening and took the rare step of publicly responding to the concerns around approving a COVID-19 vaccine for children on September 10. .  In addition to vowing to adhere to strict safety standards, FDA stated clinical trials are required to have a “follow-up period for safety data of at least about two months,” indicating a change from the previously requested six-month follow-up period.

The Timeline, Revised

With the FDA apparently open to a shorter follow-up period for safety data, what does the approval timeline look like now?  At the the Morgan Stanley Global Healthcare Conference 2021 on September 14, Pfizer CEO Albert Bourla laid out a new estimated approval timeline for children aged 5-11. 

  • Pfizer to have all safety and immunogenicity date in late September (topline results were released on September 20).
  • Pfizer to file for EUA in early October.
  • FDA to approve EUA within 3-6 weeks, meaning children aged 5-11 could get their shots as soon as late October or early November. 

Bourla also said Pfizer will likely have enough data on how well its vaccine works on children under 5 years of age as early as the end of October, putting that vaccine on the path for EUA by the FDA by the end of the year. 

This is reassuring news for parents of kids aged 5-11, to potentially have a vaccine available by Halloween than, say, early 2022.  But let’s not get our hopes up as COVID-19 has proven itself to be an incredibly unpredictable virus, and changing conditions could cause scientists and regulators to shift their approval considerations once again.

FDA

What’s Taking FDA So Long to Fully Approve Pfizer’s COVID-19 Vaccine?

by Matt Gontarchick

It took the Food and Drug Administration (FDA) just three weeks to issue an emergency use authorization (EUA) for Pfizer’s COVID-19 vaccine in December 2020 when Pfizer submitted the request.  In contrast, it’s been over two months since Pfizer initiated a “rolling submission” of its biologics license application (BLA) for its vaccine on May 7, and FDA has yet to comment on its timeline for approval.  Amid growing calls for FDA to fully approve Pfizer’s vaccine, what’s making the review process take so long?

Why the Push for Full Approval?

Many people believe full approval of Pfizer’s COVID-19 vaccine will help get more shots into arms, which is seen as vital to protecting Americans from the rapidly spreading Delta variant.  According to data from the Centers for Disease Control and Prevention posted on July 6, the Delta variant makes up 51% of new COVID-19 cases in the US.  Additionally, studies show the Delta variant is at least 40% more transmissible than the Alpha variant, which was previously the country’s dominant variant.  The surge in the Delta strain comes as many Americans remain vulnerable to COVID-19, as only 67% of Americans have received at least one COVID-19 shot, and the pace of vaccinations has dropped off considerably in recent weeks. 

Full approval of the COVID-19 vaccine is one way public health experts believe could convince more Americans to roll up their sleeves, which addresses vaccine hesitancy, a sentiment echoed by several major elected officials.   In June, President Joe Biden said going from “temporary approval to full approval” would “increase the number of people” willing to get vaccinated.  Similarly, Arkansas Governor Asa Hutchinson, whose state has some of the nation’s lowest vaccination rates, remarked in June that full approval is needed to combat vaccine hesitancy.  According to a Kaiser Family Foundation poll from May 2021, 32% of unvaccinated adults said full approval of one of the currently authorized vaccines would make them more likely to get vaccinated.

Furthermore, fully approving the vaccine will allow for more businesses and organizations to mandate the COVID-19 vaccine, which could help increase vaccination rates.  While several hospitals and health systems such as Houston Methodist and Trinity Health have mandated the vaccine for their employees, some health systems like Beth Israel Leahy Health in Boston are holding off until a vaccine is fully FDA-approved.  Even though lawsuits against vaccine mandates have so far held up in court, many employers and organizations seem to be holding off on mandating  employees to get the vaccine out of fear of litigation.   Even the US Army has communicated to servicemembers that vaccination won’t be mandated until “full FDA licensure.”

What’s the Hold Up?

The reason for FDA’s longer process for fully-approving Pfizer’s COVID-19 vaccine is due to the fact that the business of issuing a BLA is more intensive than an EUA.   For an EUA to be issued, companies need to provide the FDA data that demonstrates efficacy and safety from a Phase 3 trial with a median follow-up period of at least two months.  In contrast, a BLA requires FDA to look through at least six months of clinical trial data as well as a close examination of the company’s manufacturing process, both of which take additional time.  Dr. Paul Offitt, a member of FDA’s Vaccines and Related Biological Products Advisory Committee,  commented in December 2020 that Merck’s BLA submission for its 70,000-person rotavirus vaccine trial contained enough pages to exceed the height of the Sears Tower, a 1,450-foot skyscraper in Chicago currently known as the Willis Tower.

There are benefits for drug manufacturers in getting their products fully approved.  According to former FDA Commissioner Dr. Robert Califf, a BLA would allow Pfizer to being marketing its vaccine directly to consumers.  Additionally, full approval would open the door to Pfizer increasing the price of its vaccine post-pandemic, potentially generally billions of dollars for the company.

When Will the Vaccine Be Fully Approved?

Unfortunately, FDA has yet to shed any light on its timeline for fully approving the Pfizer vaccine.  In late June, an FDA spokesperson  told The Hill that the agency “cannot comment on individual applications before it.”  More recently, the FDA told Army Times on July 2 that timelines for approval “may vary depending on a number of factors.” 

While fully approving a vaccine normally takes between 8-12 months, there is reason to believe Pfizer will receive a decision from the FDA soon. Former FDA scientist Jesse Goodman said in June that the FDA might not complete its review process for another 3-4 months, meaning a BLA might not come until  September or October.  Notably, Goodman cautions against fully approving the vaccine too quickly, as it could “undermine confidence” in the vaccine. 

Ultimately, FDA is in a tough position.  As a full review of the Pfizer vaccine continues, the agency must strike a balance between ensuring the American people can benefit from a fully approved vaccine in a timely manner without giving off the sense that the BLA was issued too quickly.  Absent any communication from FDA, however, vaccine observers have no choice but to sit and wait.