2020 Drug Safety: CDER spotlights COVID-19 activities, nitrosamine contamination

Regulatory NewsRegulatory News | 18 February 2021 |  By 

COVID-19 was a big safety focus in 2020 for the US Food and Drug Administration (FDA), from the evaluation of drugs for emergency use authorization (EUA) to surveillance for critical drug shortages and medical product supply chain disruptions.

The 2020 Drug Safety Priorities report from the FDA’s Center for Drug Evaluation and Research (CDER) chronicles a busy year in safety monitoring and enforcement, including COVID-related activities, nitrosamine impurities, and regulation of opioid reversal agents.  

“Although significant effort in 2020 was spent battling the COVID–19 pandemic, CDER continued to complete its critical work to ensure the safety of the medicines on which millions of patients rely,” Patrizia Cavazzoni, MD, CDER’s acting director, wrote in the report.

COVID activities
The Center’s COVID-19 related efforts included reviewing safety data as part of the overall benefit-risk assessment for products submitted for EUA and new drug application (NDA) approval, conducting surveillance on safety concerns and medication errors related to COVID-19 products, and developing pandemic-related guidance documents on REMS requirements and postmarket adverse event reporting.

Among the high-profile EUAs was a high-profile March 2020 decision to allow the use of the anti-malarial drugs hydroxychloroquine and chloroquine for certain hospitalized COVID-19 patients who did not have access to a clinical trial. The agency ultimately revoked that EUA in June, based on results of a large, randomized clinical trial in hospitalized patients showing no benefit and ongoing serious cardiac adverse events.

In May, the agency issued an EUA for Veklury (remdesivir, Gilead), an antiviral drug shown to shorten the time to recovery for COVID-19 patients. The initial EUA covered use only in hospitalized patients with severe COVID-19, but in August the agency expanded the EUA to include all hospitalized patients being treated for COVID-19. In October, the agency granted regular approval of the drug for hospitalized adults and pediatrics patients aged 12 and over. CDER also expanded the EUA to include children under 12 years who are hospitalized with COVID-19.

In November, CDER issued an EUA for the monoclonal antibody bamlanivimab for the treatment of certain adult and pediatric patients with mild-to-moderate COVID-19. The same month, the agency issued an EUA for the rheumatoid arthritis drug Olumiant (baricitinib, Lilly) in combination with remdesivir to treat suspected or laboratory-confirmed COVID–19 in hospitalized adults and pediatric patients 2 years or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

The center also took several actions to help protect against contaminated hand sanitizers, including issuing warnings to consumers, warning letters to manufacturers, and initiating voluntary recalls of some products.
As part of the effort to monitor of the medical product supply chain, CDER issued 38 enforcement discretion decisions to increase supplies of heparin, albuterol, etomidate, midazolam, propofol, and others.
CDER also took on fraud in the age of COVID-19. The Center issued 90 warning letters to companies marketing products that fraudulently claimed to diagnose, cure, mitigate, treat, or prevent COVID-19, as well as 11 warning letters to Internet pharmacies selling unapproved drugs claiming to treat COVID-19.

Postmarketing activities
Aside from the focus on COVID-19, CDER continued with work on postmarket safety more broadly. CDER issued a Risk Evaluation and Mitigation Strategy (REMS) for three new drugs in 2020: Fintepla (fenfluramine hydrochloride, Zogenix), Blenrep (belantamab mafodotin-blmf, GSK), Xywav (calcium, magnesium, potassium, and sodium oxybates, Jazz), as well as a shared-system REMS for pomalidomide.

It was also an active year for the agency’s Sentinel System, which began in 2008 and uses a network of databases to provide electronic medical product safety surveillance. The system was used as part of the COVID-19 response to monitor for national and regional drug shortages in critical medications, describe the course of illness among hospitalized COVID-19 patients, evaluate the use of computable phenotypes to identify COVID-19 positive patients in real-world data, and assess the occurrence of coagulopathy and its risk factors in hospitalized COVID-19 patients.

In July, the agency launched the Sentinel Initiative’s new website, which is aimed at improving it usability.
In November, the agency held a Sentinel public training session to assess questions related to maternal health and pregnancy, including how the system links and uses mother and infant data to assess medical product use during pregnancy.

FDA also continued its efforts to keep drugs contaminated with nitrosamines off the market. In 2020, the agency took actions related to nitrosamine contamination in ranitidine, metformin, and rifampin and rifapentine. Notably, in April, the agency requested that manufacturers withdraw all prescription and over-the-counter ranitidine medications from the market immediately after determining that NDMA impurity could increase over time in ranitidine or when stored above room temperature (RELATED: FDA seeks withdrawal of heartburn drugs due to new carcinogen concerns,” Regulatory Focus 01 April 2020).

Combating opioid dependence
CDER had some key achievements in its work to support recovery from opioid use disorder and reduce overdose deaths. In July, the agency issued a Drug Safety Communication with recommendations to increase access to the opioid reversal agent naloxone. For example, FDA required manufacturers of opioid pain medicines used treat opioid use disorder to add new recommendations about naloxone to the prescribing information. In August, the FDA approved a supplemental NDA to provide a shelf-life extension for Narcan (naloxone hydrochloride) nasal spray, from 2 years to 3 years. The agency also published final guidance for industry on endpoints for demonstrating effectiveness of drug for treatment of opioid use disorder.


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Tags: CDER, coronavirus, FDA, US

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