Facet Life Sciences Quarterly Update Q1 – 2023

INDUSTRY FIRST FOR MEDICAL DEVICES:  

Facet is the first organization to work with the FDA and a medical device Sponsor to prepare and submit a combination product 510(k) using the electronic Submission Template And Resource (eSTAR) template!  Per FDA’s guidance, Electronic Submission Template for Medical Device 510(k) Submissions (Sept 2022), the eSTAR is an interactive PDF guided submission preparation tool that is intended to help Sponsors prepare and submit comprehensive and complete medical device submissions entirely in electronic format.  Submission of 510(k) applications to FDA using the eSTAR format has been voluntary since 2021, but will be required for tradition, special, and abbreviated 510(k)s and De Novo applications starting on October 1, 2023.  After obtaining agreement from the FDA to submit an eSTAR for a device-led combination 510(k), Facet helped a small ex-US company prepare and successfully submit their application electronically for Agency review.

CLINICAL HOLD LIFTED:   

Facet helped a small pharmaceutical company to obtain agreement from FDA to lift clinical hold for an early dose escalation trial.  Based on findings from one nonclinical toxicology study showing CNS effects, FDA raised concerns regarding the proposed dose escalation in an early phase clinical trial in both written communication and in a subsequent teleconference.  After the meeting, Facet and the Sponsor worked together to set the strategy for our response.  We prepared a compelling, data-driven rationale using human PK data collected from cohorts who received lower doses and proposed conservative clinical stopping rules to justify proceeding with the next dose in the study.  FDA accepted our scientific position, and the study was permitted to proceed.  If you are a small company on clinical hold or are worried you might be at risk for clinical hold, click here to talk to a Facet regulatory expert about your program.

• Facet only works with smaller life sciences companies, academic institutions, or nonprofit organizations to help get their products to and through FDA
• Facet was regulatory lead for two US marketing approvals in 2022 – 1 new chemical entity and 1 505(b)(2) product
• Facet helps organizations determine a sound, streamlined development plan which outlines the necessary nonclinical, CMC, and clinical information needed to achieve a specific regulatory milestone.  For some organizations, this means IND green light, for other organizations, it means taking a product “all the way” to marketing approval.
• Facet regularly meets with FDA to discuss drug and biological product development both in formal and informal meetings.

Rare Disease Day: 

On February 27, 2023, FDA hosted a virtual Rare Disease Day the purpose of which was to explore patient and patient advocate engagement in supporting the development of products for rare diseases.  During the meeting, FDA outlined the common challenges in developing products for rare diseases, including poorly understood natural history, small patient populations, ethical issues associated with conducting clinical trials in pediatric patients, phenotypic/genotypic diversity within a rare disease, difficulty identifying outcome measures and biomarkers to establish clinically meaningful benefits, and business-related challenges associated with economically infeasible indications.

FDA also discussed Project Catalyst, a program under the Oncology Center for Excellence which is intended to provide innovation and development support to small organizations (e.g., academia, start-ups).  Their educational initiative, entitled Oncology Regulatory Expertise and Early Guidance (OREEG) is a great place for organizations to obtain product-type advice to inform product-specific development.  The program includes the ability to direct specific questions to FDA experts as well as participate in Accelerator Innovation Discussion (AID) meetings prior to any formal meetings with FDA.

Of note, FDA has observed that most companies in the rare disease space are lacking regulatory experience and strongly recommended that they partner with regulatory and development consulting organizations, like Facet, that can help bridge the science-regulation gap.

Diagnostic radiopharmaceuticals now deemed “drugs” by Congress: 

Congress passed an amendment to the Food, Drug, and Cosmetics Act (FD&C Act or FDCA) within the omnibus appropriations bill that passed on December 23, 2022.  The Genus decision and regulation of contrast agents and radiopharmaceutical drugs was included in this amendment and is now final.  Specifically, any contrast agent, radioactive drug, or OTC monograph drug shall be deemed to be a drug under section 201(g) and not a device under section 201(h).  The term “contrast agent” is defined as a product that is used in conjunction with a medical imaging device and meets the definition of a diagnostic radiopharmaceutical (21 CFR 315.2 and 601.31) or an agent that improves the visualization of structure or function within the body by increasing the relative difference in signal intensity within the target tissue, structure, or fluid.

Total submissions to FDA January – March 2023:  41 (on average over 3 submissions a week!) 

Early-stage development highlights:  preparation/submission of 7 new INDs and submitted over 20 IND amendments (e.g., new protocols/amendments, CMC updates, nonclinical study reports, annual reports, safety reporting/DSURs); conducted formal meetings with CBER, CDER, and CDRH; were involved in an Expanded Access program for pediatric patients with a rare disease; prepared several gap analyses and regulatory development plans; helped several organizations obtain orphan designation for their products, ongoing review of public-facing information (e.g., websites, flyers, conference presentations) about investigational products; helped 1 organization find specialty investigational CDMO; and completed 1 CMC vendor qualification

Lage-stage development highlights:  preparation of Phase 3 clinical regulatory strategies; active participation in 1 commercial launch; supported removal of 1 drug from drug shortages list; supported 1 organization to secure external funding; supported 1 organization to divest product; helped 1 organization select commercial CDMO; and ongoing ad promo strategy and document review