Logistics and supplies are not the sexy part of drug and device development, but they’re what makes using a diagnostic, therapy or vaccine possible.
During a massive disaster or a pandemic, securing the necessary manufacturing capacity, needles, syringes, vials, properly labeled caps, reagents and other supplies is as critical as the development of the product itself. Some experts have been warning about these needs since COVID-19 first began spreading outside of China. Now members of Congress are sounding the alarm.
Echoing concerns raised in a recent whistleblower complaint filed by former Biomedical Advanced Research and Development Authority (BARDA) Director Rick Bright, 25 U.S. lawmakers, from both parties, wrote to House leaders Wednesday urging them to address the shortage of syringes, needles and other materials that will be needed to effectively administer a coronavirus vaccine while maintaining access to other necessary vaccines and drugs.
“Deploying a vaccine nationwide will require a massive manufacturing and logistical effort the likes of which our nation has never seen before,” the House members, led by Rep. Josh Gottheimer (D-N.J.), said in the letter. At the current manufacturing capacity, it would take more than a year to produce the supplies necessary to administer the vaccine to everyone in the country – and that could impact the availability of other vaccines and therapies.
“Rapidly producing and deploying millions or billions of vaccine doses greatly exceeds our current domestic manufacturing capacity and may require the repurposing of manufacturing facilities or the construction of new ones,” according to the letter. “We need excess capacity to supplement existing biopharmaceutical manufacturing which is necessary to produce the medications we need.”
That manufacturing need is addressed in the HEROES Act, which the Democratic-controlled House passed last month on a party-line vote. However, while the legislation includes requirements to expand and enhance the domestic manufacturing capacity of vaccines, it doesn’t address the supplies needed to administer a pandemic vaccine, according to the letter. (The HEROES Act was read in the Senate for the second time Monday and placed on the legislative calendar.)
“It is critical that we do not repeat the same mistakes made when we faced similar crises in the past,” the lawmakers told House Speaker Nancy Pelosi (D-Calif.) and Republican Leader Kevin McCarthy (Calif.). Their letter referenced the delayed response in 2009 to the H1N1 pandemic that led to a slow rollout of supplies in quantities insufficient to meet the demand for the vaccine.
Thus, many vaccine doses weren’t available until after H1N1 incidences had fallen. As a result, only about 90 million of the 162 million doses, or 55%, of the H1N1 vaccine produced for the public were administered, the letter said, citing the CDC.
To ensure history doesn’t repeat itself, the lawmakers asked Pelosi and McCarthy to include “robust funding” in future COVID-19 legislative packages to address the supply manufacturing need through BARDA, the Strategic National Stockpile and the private sector. According to the letter, the legislation should:
- encourage cooperation with the private sector through joint ventures and use of facilities and equipment needed to ramp up production of medical supplies;
- expand and broaden the medical countermeasure manufacturing base across multiple regions;
- create a domestic reserve of critical medical supplies, including syringes, needles and other materials;
- increase the emergency stockpile of those supplies.
Meanwhile, companies that are developing potential vaccines have been considering the limited supplies and looking for ways to stretch them since January. Speaking at an International Federation of Pharmaceutical Manufacturers & Associations’ (IFPMA) briefing last week on COVID-19 vaccine development, Pascal Soriot, executive director and CEO of Astrazeneca plc, said the challenge, once a vaccine is developed, won’t be manufacturing the vaccine – it will be filling vials with the product. There just are not enough glass vials for the billions of doses that will be needed, he added. One solution that’s being explored is to fill the vials with multiple doses instead of a single dose.
Paul Stoffels, vice chairman of the executive committee and chief scientific officer at Johnson & Johnson (J&J), agreed that being able to fill will be the big bottleneck in vaccine production. Instead of scaling up for vaccine production, he said J&J is “scaling out” by building additional plants in the U.S., Europe and Asia so it will have the capacity to fill and finish. Because of the limited supply of vials, J&J is putting multiple doses in each vial. Having five to 10 doses in a vial is essential to coping with the volume needed, Stoffels said, as it will make it easier to distribute a vaccine and address capacity issues.
“The challenge is daunting,” IFPMA Director General Thomas Cueni said of the manufacturing and supply bottlenecks for a COVID-19 vaccine going forward. Globally, as many as 15 billion doses may be needed. Cueni put that into perspective, saying that about 5 billion doses are manufactured each year for seasonal influenza.
Potential for medical errors
What wasn’t discussed at the briefing was the potential for medical errors due to the switch to multiple doses per vial. The FDA is already warning about such errors with other products as the urgency in dealing with supply shortages is resulting in temporary container changes. Wednesday, the agency alerted health care professionals about the temporary absence of the warning statement “paralyzing agent” that’s usually embossed on the vial caps of two injected neuromuscular blocking drugs.
COVID-19 has increased the use of vecuronium bromide and rocuronium bromide in intensive care unit patients requiring mechanical ventilation, while also causing supply chain disruptions contributing to a shortage of product components, such as the embossed vial caps, the FDA said.
To increase the supply of the two injectable drugs, the FDA is allowing vecuronium bromide to be distributed through September 2020 without the embossed cap and rocuronium bromide to be distributed through next month without the warning on the cap.
Since the absence of the warning statement on the cap could make the vials look like other drugs when stored upright in a cabinet drawer or on a shelf, the FDA is asking health care providers to take precautions to avoid medical errors that could lead to death. For instance, they should label the vial caps, avoid storing the product in a way that only the cap is visible, and scan the barcode when stocking medication cabinets and preparing or administering a product.