FDA announces efforts to tackle supply problems causing drug shortages
US Food and Drug Administration (FDA) Commissioner Scott Gottlieb, MD, today announced the formation of a new task force to address drug shortages and long-term strategies for preventing them.
In a statement, Gottlieb said though the number of new drug shortages has declined since 2011, the agency continues to see ongoing shortages of medically necessary products. He added that even short supplies of a small number of key drugs can put a serious burden on health providers, which sometimes impact patient care.
"While we've made progress to mitigate individual shortages, we haven't firmly impacted the underlying structural concerns that give rise to these recurring challenges," he said.
Lawmakers have urged the FDA to develop new proposals that have a longer-term impact on the shortages and have asked the FDA and other federal agencies if they need more authority to ensure that patients have the drugs they need and have requested recommendations for policy changes to address the shortages, Gottlieb said.
The Drug Shortages Task Force will be headed by Keagan Lenihan, the FDA's associate commissioner for strategic initiatives, and include senior leaders from the FDA and other federal agencies. Gottlieb said the group's mission is to look more deeply into the reasons for persistent shortages and for solutions that address the underlying causes. He noted that the task force's work will expand on a group created by the FDA Safety and Innovation Act of 2012, which gave the agency new authorities to address drug shortages.
Gottlieb emphasized that lasting solutions can't be addressed by the FDA alone, and he acknowledged that many drugs in short supply are low-profit generic medicines and sterile parenteral drugs that are challenging to make in an industry marked by consolidation. "This has resulted in fewer and fewer manufacturers for certain key products. The result is very little margin for error in this space," he said, adding that lack of investment in manufacturing creates conditions that lead to production stoppages.
Along with examining the FDA's authority, the group will also explore possible incentives to expand manufacturing capacity, whether it would be useful to develop a critical drug list that merits stronger interventions to prevent shortages, and the possibility of coupling regulations with financial incentives. To encourage feedback from the industry, other stakeholders, and the public, Gottlieb said the FDA will hold a public meeting sometime in the next several months.
Jul 12 FDA statement
Two phase 2 TB vaccine trials show reduction in sustained infections
Results from two tuberculosis (TB) vaccine candidate phase 2 trials show both were effective in reducing the rate of sustained infections in high-transmission settings, according to a study today in the New England Journal of Medicine, but H4:IC31, one of the candidate vaccines, did not reduce transmissions at a statistically significant rate.
The proof-of-concept study looked at two TB vaccine candidates, H4:IC31, a candidate subunit vaccine that consists of a recombinant fusion protein (H4) and IC31 adjuvant, and the primary bacille Calmette–Guerin (BCG) vaccine. The research was conducted in South Africa, where 930 children ages 12 to 17 who had already received BCG in infancy were either revaccinated with BCG or given H4:IC31. All trial participants tested negative for HIV and TB at the beginning of the trail.
The efficacy of the H4:IC31 vaccine for the prevention of sustained QuantiFERON-TB Gold In-tube assay (QFT) conversion was 30.5%. In the BCG group, the efficacy of revaccination for the prevention of sustained QFT conversion was 45.4%, and 48.2% efficacy was observed at the end of the trial. The results for H4:IC31 were deemed not statistically significant.
The authors conclude that their trials show a promising result in BCG revaccination in patients who are TB-free. Previous studies have shown a wide range of BCG efficacy against initial Mycobacterium tuberculosis infection, from 27% to 71%.
"The efficacy of the primary BCG vaccine against disease is highly variable in different populations; efficacy is thought to be greatest in persons without previous mycobacteria exposure and may last for 10 years. Our findings suggest that BCG revaccination of QFT-negative adolescents may provide additional benefit," the authors said.
Jul 12 N Engl J Med study
Using fractional doses of yellow fever vaccine leaves many questions
In a letter today also published in the New England Journal of Medicine, three researchers tackle fractional dosing and the yellow fever vaccine.
First used in the Democratic Republic of the Congo (DRC) in 2016, fractional dosing involves inoculating recipients with one fifth of the yellow fever vaccine during an outbreak. The dose-saving measure helps stretch global supply of the vaccine, and was used in Brazil in 2017 during another outbreak of the flavivirus.
Existing yellow fever vaccines contain doses between 12,874 and 43,651 international units (IU), far above the WHO’s recommended minimum of 1,000 IU.
Until 2016, there were only three published studies on fractional dosing, but all showed overwhelming (98%) seroconversion among people who were seronegative at the time of vaccination. Follow-up studies published earlier this month showed that even small doses of the vaccine offered protection for up to 8 years.
But the authors, led by Kristen Vannice, PhD, MHS, say fractional dosing is a complex issue; WHO's recommended minimum dose is based on studies in animals rather than dose-finding studies in humans, and there is little known about fractional dosing in children.
"Although available evidence supports the use of fractional-dose vaccination when needed, a larger evidence base will be important to ensure optimal use and protection," the authors conclude.
Jul 12 N Engl J Med letter
Jul 5 CIDRAP News scan on latest study
Scientists isolate influenza B virus in pigs, showing zoonotic threat
For the first time, scientists isolated naturally occurring influenza B viruses in pigs. Influenza and Other Respiratory Viruses published the report today.
Researchers isolated the virus from Taiwanese swine. From 2007 to 2017, 15,983 swine serum samples were collected from 1,039 farm visits under active surveillance. In 2014, three samples were positive for influenza B. Genetic analysis showed the viruses to be grouped with B/Taiwan/13/2013 and B/Taiwan/113/2014 in the same cluster of the B/Brisbane/60/2008 genetic clade of Victoria lineage.
In addition to the three positive samples, antibodies against swine influenza B viruses were detected in 31 serum samples.
"Public health concerns might arise from the finding that [influenza B viruses] could be transmitted naturally from humans to pigs, even cross-species infections are sporadic and accidental currently in Taiwan. It implies a cycle of human-swine-human transmission could be or might have been initiated as some of [influenza A viruses] did in human and swine populations," the authors concluded.
Jul 12 Influenza Other Respir Viruses study
Russia, Taiwan report more high-path H5 avian flu outbreaks
In the latest highly pathogenic avian flu developments, Russia reported eight more H5 outbreaks in backyard poultry in the west, and Taiwan reported one more H5N2 outbreak at a commercial poultry farm, according to notifications from the World Organization for Animal Health (OIE).
In Russia, the latest detections occurred in four oblasts: Orlov, Rostov, Kursk, and Nizhegorod. The outbreaks began from Jun 26 to Jul 9, killing 6,116 of 616,350 susceptible poultry. The outbreaks are part of ongoing avian flu activity in western Russia that began on early June.
Though the OIE report doesn't specify an H5 subtype, an updated risk assessment on Jul 9 from the UK Department for Environment, Food, and Rural Affairs (DEFRA) said H5N8 was involved in Russia's outbreaks.
Meanwhile, Taiwan's latest outbreak—part of activity under way since early 2015—struck a turkey farm in Yunlin County. The event began on Jul 2, killing 161 of 771 birds.
Jul 11 OIE report on H5 in Russia
Jul 9 DEFRA updated avian flu risk assessment
Jul 12 OIE report on H5N2 in Taiwan
In low-pathogenic avian flu developments, France reported an H7N7 detection at a mallard farm housing 10,000 ducks in Val-d'Oise department in the north central part of the country. The virus was found on Jun 6 during regular surveillance. The birds were contained, and repeat tests on Jul 5 were negative. The country's last outbreak involving low-path H7N7 was reported in January 2017.
Jul 9 OIE report on H7N7 in France