Pharmaceutical Technology Editors

Providing Submissions in Electronic Format– Postmarketing Safety Reports

, the last in a series of guidance documents intended to assist industry when making certain regulatory submissions in electronic format to FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER).

The guidance is intended for any party with postmarketing safety reporting responsibilities for approved and unapproved human drug products and licensed biological products, excluding vaccines. The guidance also provides recommendations on how to submit postmarketing safety reports that FDA can process, review, and archive. A revised draft version of this guidance was issued in June 2014, and minimal changes were made in the final guidance.

The guidance provides general information on the electronic submission of postmarketing safety reports under the following provisions, according to FDA; “21 

] 314.80 and 314.98 (regarding products with approved new drug applications (NDAs) and abbreviated new drug applications (ANDAs), respectively, including combination products or drug constituent parts with approved NDAs or ANDAs2; 21 

 600.80 (regarding products with approved biologics license applications (BLAs), including combination products or biological product constituent parts with approved BLAs)3; 21 

 part 4, subpart B (requiring additional reports for combination products with approved NDAs, ANDAs, or BLAs); and 21 CFR 310.305 (regarding prescription drug products marketed for human use without approved NDAs or ANDAs, including prescription drug products that are compounded.”

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FDA has issued the final guidance on electronic postmarketing safety reports in a series of guidance documents. 

FDA Issues Final Guidance on Electronic Postmarketing Safety Reports

Pfizer and Biohaven Pharmaceutical Holding Company announced on April 27, 2022 that the European Commission (EC) has granted marketing authorization for VYDURA (rimegepant), a calcitonin gene-related peptide (CGRP) receptor antagonist, for both the treatment of migraine with or without aura and prophylaxis of episodic migraine in adults who have at least four migraine attacks per month.

The medicine is an orally disintegrating tablet and is the first medicine to be approved for both acute and prophylactic treatment of migraine in the European Union (EU). According to the press release, approximately 1 in 10 people are living with migraines in Europe alone. Migraines disproportionally affects women by three to four times compared to men globally.

The marketing authorization follows the recommendation for approval by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) in February. The approval will be valid for all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. Approval is expected to follow shortly in the United Kingdom.

“Today’s approval marks a huge step forward for patients in Europe who are living with migraine. Migraine is often overlooked and undertreated, resulting in substantial disability with suboptimal care for patients,” commented Professor Peter Goadsby, director of the National Institute for Health and Care Research (NIHR) Clinical Research Facility and Professor of Neurology at King’s College London. “VYDURA’s promising efficacy and favorable benefit-risk profile spark hope for people in need of new migraine treatment options. This approval has the potential to advance the standard of care for migraine in the EU and I am hopeful it will improve the quality of life for many people living with the burden of this prevalent neurological disease.”

VYDURA has been granted marketing authorization by the European Commission for both acute treatment of migraine and prophylaxis of episodic migraine. 

Migraine Treatment Granted Marketing Authorization by European Commission 

Moderna announced on April 28, 2022 that it has submitted a request for emergency use authorization (EUA) to FDA for its COVID-19 vaccine to be used in children six months to under six years of age. The company states that similar requests are underway with international regulatory authorities. The vaccine, called SPIKEVAX, is currently authorized for use for active immunization against COVID-19 in individuals aged 18 years or older.

The submission comes after positive results from a study conducted to gauge the safety and efficacy of the vaccine for use in young children. The efficacy estimates were shown to be similar to vaccine efficacy shown in adults. The results showed a robust neutralizing antibody response in children six months to six years of age.

Moderna is also studying booster doses for pediatric patients. The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID). The EUA submission for children ages 6 months to under 6 years will be complete next week.

"We are proud to share that we have initiated our EUA submission for authorization for our COVID-19 vaccine for young children," said Stéphane Bancel, CEO of Moderna, in a press release. "We believe mRNA-1273 will be able to safely protect these children against SARS-CoV-2, which is so important in our continued fight against COVID-19 and will be especially welcomed by parents and caregivers."

Moderna has filed for emergency use authorization of its COVID-19 vaccine for use in young children six months to under six years of age.

Moderna Submits EUA of COVID-19 Vaccine for Use in Young Children

Daiichi Sankyo and AstraZeneca’s ENHERTU (fam-trastuzumab deruxtecan-nxki) has been granted breakthrough therapy designation (BTD) in the United States for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer. It is meant for those who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. Those with hormone receptor (HR) positive breast cancer should also have either received or be ineligible for endocrine therapy.

ENHERTU is being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. It is a specifically engineering HER2 directed antibody drug conjugate (ADC). The drug candidate demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) versus the current standard of care, chemotherapy.

FDA’s BTD is meant to accelerate the development and regulatory review of new medicines that have the potential to treat serious conditions and address significant unmet medical needs. It is granted to medicines that have demonstrated substantial improvement on a clinically signific ant endpoint over available medicines.

“Historically, only patients with HER2 positive metastatic breast cancer were shown to benefit from HER2 directed therapy. DESTINY-Breast04, in which ENHERTU showed a clinically meaningful survival benefit in patients with HER2 low metastatic breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients,” said Ken Takeshita, MD, global head of R&D, Daiichi Sankyo, in a press release. “This Breakthrough Therapy Designation acknowledges the potential of ENHERTU to fulfill an unmet medical need and we look forward to working closely with the FDA to bring the first HER2 directed therapy to patients with metastatic breast cancer whose tumors have lower levels of HER2 expression.”

ENHERTU has been granted breakthrough therapy designation in the US for patients with HER2 low metastatic breast cancer.

ENHERTU Granted Breakthrough Therapy Designation in US

Autolus Therapeutics, a biopharmaceutical company focused on T cell therapies, announced on April 25, 2022 that FDA has granted regenerative medicine advanced therapy (RMAT) designation to its gene therapy obecabatagene autoleucel (obe-cel).

The therapy is a CD19-directed autologous chimeric antigen receptor (CAR)-T therapy meant for the treatment of adult relapsed/refractory B-Acute Lymphocytic Leukemia (B-ALL). FDA grants RMAT designation to drug candidates that may address significant unmet medical needs in patients with serious or life-threatening conditions. RMAT is designed to accelerate the drug development process by facilitating and expediting development and regulatory review. Obe-cel has been previously granted Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) and Innovative Licensing and Access Pathway (ILAP) by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom.

“RMAT designation is an important regulatory milestone for obe-cel and highlights its potential to address the unmet medical need for adult patients with relapsed and refractory B-ALL,” said Dr. Christian Itin, CEO of Autolus. “RMAT designation from FDA, PRIME designation from EMA and ILAP designation from MHRA facilitate regulatory interactions with key health authorities and supports our drive to bring this innovative therapy to patients as quickly as possible.”

FDA has granted regenerative medicine advanced therapy (RMAT) designation to Autolus’ CAR-T cell therapy obe-cel. 

FDA Grants RMAT Designation to Autolus’ CAR-T Cell Therapy

The Spheronizer from DIOSNA Dierks & Söhne

The Spheronizer from DIOSNA Dierks & Söhne is a space-saving solution that allows for granulation and pelletizing of particles during the development of oral solid dosage forms. It aims to provide pharmaceutical manufacturers with high-quality pellets on a laboratory scale and forms an ideal basis for subsequent processes. 

The product is compatible with the laboratory mixer P 1-6 from DIOSNA, which can add an additional process step with the pelletizer option. The Spheronizer bowl can be docked onto the existing base machine of the pharmaceutical mixer or be used as a stand-alone machine.

The Spheronizer from DIOSNA Dierks & Söhne is designed for the granulation and pelletizing of particles during the development of oral solid dosage forms. 