Pharmaceutical Technology Editors

Gilead Sciences announced on April 25, 2022 that FDA has approved a supplemental new drug application (sNDA) for Veklury (remdesivir) for the treatment of pediatric patients who are either hospitalized with COVID-19 or have mild-to-moderate COVID-19 and are considered high risk for progression to sever COVID-19, including hospitalization or death. Patients must also be older than 28 days and weigh at least 3 kg.

This approval follows the recent sNDA approval for Veklury for adults and adolescent patients who are at high risk of progression to severe COVID-19. For pediatric patients who are at high risk for COVID-19 disease progression, a three-day Veklury treatment regimen is recommended to help prevent hospitalization. For currently hospitalized pediatric patients who do not require invasive mechanical ventilation and/or ECMO, a five-day treatment course is recommended.

“This approval means that remdesivir can potentially provide meaningful clinical improvement, by reducing disease progression and helping children recover from COVID-19 more quickly,” said Amina Ahmed, MD, Atrium Health-Levine Children’s Hospital in Charlotte, NC, in a press release. “We need proven antiviral treatment options, like remdesivir, that can help treat some of the most vulnerable in our society: children.”

“The expanded indication for Veklury for the treatment of children is a testament to the safety, tolerability and efficacy profile of this therapy, which has remained the foundational antiviral for COVID-19 treatment,” added Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences. “Effective and tolerable options for children require our best science and a dedicated focus. With the recent opening of our Gilead Pediatric Center of Excellence in Dublin, which is responsible for coordinating pediatric clinical trials for treatments for HIV, hepatitis B and COVID-19, we will continue our research to help address unmet treatment needs for children.”

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FDA has approved Veklury to treat COVID-19 in pediatric patients under 12 years of age.

FDA Approves Veklury for Treatment of COVID-19 in Pediatric Patients

Pfizer has issued a voluntary nationwide recall of five lots of Accupril (Quinapril HCl) tablets distributed by Pfizer due to the presence of a nitrosamine, N-nitroso-quinapril, that is above the Acceptable Daily Intake (ADI) level.

Accupril is meant to lower blood pressure to treat hypertension, as well as for the management of heart failure as adjunctive therapy in addition to conventional therapy such as diuretics and/or digitalis. Pfizer is not aware of any adverse events that have been assessed to be related to this recall.

Nitrosamines are common and everyone is exposed to some level of them. However, if exposed to them above acceptable levels over long periods of time, they may increase the risk of cancer. While long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk, Pfizer states that there is no immediate risk to patients taking this medication. Patients currently taking this product should consult with their health care provider about alternative treatment options.

The product lots, DR9639, DX8682, DG1188, DX6031, and CK6260, were distributed nationwide to wholesalers and distributers in the United States and Puerto Rico from December 2019 to April 2022. Pfizer has notified direct consignees by letter to arrange for return of the recalled product and urges any entities with existing inventory of the lots to cease distribution and quarantine the product immediately. The recall is being conducted with the knowledge of FDA.

Pfizer has issued a voluntary nationwide recall of lots of Accupril due to N-nitroso-quinapril content.

Pfizer Issues Voluntary Nationwide Recall of Lots of Accupril

Roche announced on April 22, 2022 that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval under conditional marketing authorization for mosunetuzumab. The drug is meant for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least two prior systemic therapies.

According to a press release, more than 28,000 people in Europe are diagnosed with FL each year. FL is the second most common form of lymphoma globally, accounting for 20% of all non-Hodgkin lymphomas (NHL) diagnosed worldwide. The majority of people with FL relapse within five years after initial treatment, and conventional treatment options are currently limited for those who have received two or more prior therapies.

If approved, mosunetuzumab will be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL. A final decision regarding the conditional approval of the treatment is expected from the European Commission in the near future.

“The majority of people with follicular lymphoma experience frequent relapses, and with each successive therapy the duration of remission and survival shortens,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, in a press release. “Today’s decision acknowledges the potential of mosunetuzumab as an efficacious, readily available, fixed-duration option, and brings the possibility of new hope to people living with this disease.”

EMA is recommending EU conditional approval of Roche’s potential first-in-class bispecific antibody mosunetuzumab for people with relapsed or refractory follicular lymphoma.

EMA Recommends EU Conditional Approval of Roche’s Mosunetuzumab

Novo Nordisk announced on April 22, 2022 that the European Medicines Agency (EMA) has issued the company a positive scientific opinion for a proposed update to the storage conditions of two human insulins.

The more flexible storage conditions will allow Actrapid (short-acting insulin) and Insulatard (intermediate-acting insulin) to be stored for four weeks outside of a refrigerator, if kept below 30 oC, prior to use if there are six months or more until the expiry date. The insulin should be stored without refrigeration once in use.

EMA’s positive scientific opinion will be used to support the flexibility and convenience for many people with diabetes in low- and middle-income countries who have limited access to reliable refrigeration or live within long distances from a clinic or pharmacy.

Insulin is temperature-sensitive and loses potency when exposed to temperatures that are too high or too low. This can be an issue for sufficient cold storage in hot climates or in areas without reliable refrigeration or electricity. Thermostability of insulin is important to maintain more accessibility to patients with diabetes globally.

“For patients receiving insulin therapy, maintaining insulin within recommended temperatures can be a source of anxiety, challenge, and poor compliance and it is not always possible to find a solution,” said Dr. Kaushik Ramaiya, honorary general secretary, Tanzania Diabetes Association, in a press release. “Creating new opportunities for established products to benefit people with diabetes in resource-constrained settings is a recognizable contribution to help address unmet needs of majority of the people with diabetes in low- and middle-income countries.”

EMA has granted Novo Nordisk a positive scientific opinion on human insulin with more flexible storage without refrigeration.

Novo Nordisk Announces Positive Scientific Opinion from EMA on Human Insulin

Pharmaceutical Quality/Chemistry Manufacturing and Controls Data Exchange

,” and is requesting comment for the electronic submission of PQ/CMC data. FDA released the draft document on March 18, 2022 and is requesting comments and feedback by May 17, 2022.

According to FDA, “this document provides draft design of Health Level 7 (HL7) Fast Health Interoperability Resources (FHIR) profiles that contain the data elements and terminologies associated with PQ/CMC subject areas and scoped to some of what is currently submitted in Module 3 of the electronic Common Technical Document (eCTD) submission.”

FDA is currently seeking feedback and comments on how the PQ/CMC data elements are represented in HL7 FHIR. The document is part of an effort intended to support future electronic acquisition and use of submitted information. The project aims to identify PQ/CMC information that would benefit from a structured submission approach. FDA has worked with the members of various HL7 workgroups, including the Biomedical Research and Regulation (BR&R) Workgroup, to develop the document.

This structured and standardized information is intended to be submitted in the Module 3 of the Common Technical Document as defined by the International Council for Harmonisation’s (ICH) M4 Common Technical Document (CTD). The document is not intended to be comprehensive in covering all eCTD product quality information.

FDA is requesting comment on draft document “Pharmaceutical Quality/Chemistry Manufacturing and Controls Data Exchange.”

FDA Requesting Comment on Pharmaceutical Quality/Chemistry Manufacturing and Controls Data Exchange 

Kite, a Gilead Company, announced on April 19, 2022 that FDA has approved commercial production at the company’s new chimeric antigen receptor (CAR) T-cell therapy manufacturing facility in Frederick, Md. Kite will use the facility to product its CAR T-cell therapy used to treat blood cancer.

The new facility will add to Kite’s existing manufacturing sites in Southern California and Amsterdam, Netherlands. According to the company, the expansion will form the largest dedicated in-house cell therapy manufacturing network in the world. Kite anticipates network capacity to increase by 50%.

CAR T-cell therapies are manufactured individually for each patient, using the patient’s own T-cells extracted from their white blood cells. The T-cells are then modified at the site with a chimeric antigen receptor to recognize, attack, and destroy their cancer cells. The therapy is then transferred back to the hospital to be infused back into the patient. It is a one-time treatment, unlike most other cancer treatments currently available.

“The FDA approval of our Maryland site marks an important milestone within our global CAR T-cell therapy manufacturing network, and will enable us to significantly expand our production capacity and further strengthen our ability to meet the needs of people living with difficult-to-treat blood cancers,” said Christi Shaw, CEO of Kite, in a press release. “Manufacturing is central to every decision we make at Kite. Our teams hold patients’ cells in their hands every day, which could mean the difference between getting a chance to live or possibly losing their battle with cancer. It must be fast and extremely high quality to give patients the best outcome.”

FDA has approved commercial production at Kite’s new CAR T-cell therapy manufacturing facility in Frederick, Maryland.