This Week at FDA: Foreign clinical trial scrutiny, botanical drugs, and an EUA declaration
Welcome to another installment of This Week at FDA, your weekly source for updates – big and small – on FDA, drug, and medical device regulation, and what we’re reading from around the web. Several top FDA officials outlined steps they are taking to bolster clinical trial inspections, especially for foreign trials, the agency is seeking input on botanical drugs, and the Department of Health and Human Services (HHS) has issued a new emergency use authorization declaration for military purposes.
The heads of FDA's drug, biologic, and medical device product centers, as well as the head of its Oncology Center of Excellence, co-published a blog post highlighting efforts to expand inspections of foreign clinical trials, improving communication with sponsors about issues with trial sites and personnel, and providing additional training to agency product reviewers to help identify clinical trial sites that may have concerns. They noted that the efforts are aimed at addressing concerns with good clinical practice (GCP) shortcomings, especially in trials conducted outside the US.
HHS has issued a broad emergency use authorization (EUA) due to a determination by the Secretary of War that there is an ongoing military emergency that involves heightened risk to military personnel who may be subject to an attack involving a chemical, biological, radiological, or nuclear agent. The EUA would facilitate the use of unapproved drugs identified and supported by the Department of War to address unmet needs for such attacks.
FDA wants public feedback on how to help streamline and advance the development of botanical drug products. The agency said it has thus far approved four such products as prescription drugs and acknowledged they present inherent complexities and unique challenges for research, product development, and regulatory review.
STAT News reported that artificial intelligence (AI) products developed by Cadence and Limbic are among four devices accepted into the FDA's TEMPO pilot program, which is intended to allow digital health companies to release their products without marketing authorization under the Medicare ACCESS model. The pilot includes Cadence’s HypertensionOS, an AI tool that autonomously manages patients with high blood pressure, and Limbic’s Unpacked, an AI voice agent that provides evidence-based talk therapy to help patients with depression and anxiety.
Several regulatory agencies, including FDA, announced they have completed a pilot project through the International Coalition of Medicines Regulatory Authorities (ICMRA), which, among other proposed manufacturing changes, evaluated the use of a recombinant endotoxin test as an alternative to the traditional Limulus Amebocyte Lysate (LAL) test that uses horseshoe crab blood and found it to be successful. The participants, led by the European Medicines Agency and also including Australia’s Therapeutic Goods Administration, Health Canada, Japan’s Pharmaceuticals and Medical Devices Agency, and Swissmedic, approved a Post-Approval Change Management Protocol (PACMP) that would allow the use of the recombinant endotoxin test and reduce the need for animal-derived materials.
FDA issued a statement that it is aware that patients may be having difficulty getting the menopausal hormone transdermal therapy patch estradiol due to an increase in demand after it asked manufacturers in November to remove a boxed warning about increased risk for breast cancer, cardiovascular disease, and dementia. The agency said it is working with the drug's manufacturers to increase supply, but insisted that while the availability of certain products or brands may vary by pharmacy or location, the patch is still available in the US.
Drugs & Biologics
The Center for Biologics Evaluation and Research (CBER) published two updated Standard Operating Policy and Procedures (SOPP), including one for agency staff to on meeting provisions of the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA). Some of the changes to the SOPP include updates to the submission requirements if an IND doesn’t exist, submission timelines if an EOP2 meeting is not held, updated responsibilities, and updated procedures on including proposed pediatric study requests (PPSRs) and Written Requests (WRs).
The biologics center also updated an SOPP for its staff on administrative processing and review management of charging requests, such as cost recovery requests, for an investigational product that is the subject of an investigational new drug application (IND) or investigational device exemption (IDE). The agency said it made changes to the document to make it more accurate, clear, and concise, added definitions, updated responsibilities, and removed Appendix A.
Ionis Pharmaceuticals' Zanvastro (zilganersen) injection was approved by FDA to treat Alexander disease for pediatric and adult patients. The agency noted that the drug is the first treatment approved for the rare and progressive neurological disorder caused by mutations in the gene that produces glial fibrillary acidic protein (GFAP), and the first to directly target the protein buildup that drives the disease.
Ultragenyx Pharmaceutical's Genglycos (pariglasgene brecaparvovec-opnr) was granted accelerated approval as a treatment to reduce daily cornstarch intake as an adjunct to nutritional management in patients 8 years and older with glycogen storage disease type Ia (GSDIa). The adeno-associated virus (AAV) vector-based gene therapy is intended to treat the rare, monogenic disease caused by deficient glucose-6-phosphatase (G6Pase) activity in the liver and kidneys.
PharmaEssentia's Besremi (ropeginterferon alfa-2b-njft) injection was approved by FDA to treat adult patients with essential thrombocythemia, a rare blood disorder that causes the bone marrow to make too many platelets, increasing the risk for blood clots and bleeding. The agency noted that the drug dosage should be increased every two weeks from 250 mcg to 500 mcg by week four.
FDA has added a boxed warning to Daiichi Sankyo's Injectafer (ferric carboxymaltose) injection to include the risk for symptomatic hypophosphatemia associated with the drug that may lead to bone softening and fracturing. The agency recommends monitoring phosphate levels in patients at risk of hypophosphatemia, as well as in those who receive a repeat course of the injection within three months of the prior course.
Medtech
FDA published two guidances addressing the development of dental devices. The agency published final guidance for sponsors developing dental composite resin devices, with recommendations on device description, non-clinical performance testing, clinical performance testing, and labeling requirements. It also published a final guidance with similar considerations for sponsors developing dental curing light devices.
Boston Scientific has reached out to customers as part of a Class I recall, asking them to cease use of its Spinal Cord Stimulator (SCS) Systems with Infinion CX Leads due to concerns that faulty leads could result in high impedance measurements or lead fractures. FDA noted that abnormal impedance measurement may cause inadequate stimulation and require lead explantation and replacement.
Following an early alert last month, Medline more recently issued a letter to customers recommending they remove all lots of affected Hudson RCI Neonatal/Infant Heated Wire Breathing Circuits and stop their use in what FDA said is a Class II recall. The company has received reports that the devices may sporadically fail, which may lead to inadequately heated or unconditioned gas that may desiccate and damage the infant patient's airway epithelium, predisposing them to bronchospasm, inspissated secretions, and airway obstruction.
