- CDRH participation in the International Medical Device Regulators Forum (IMDRF)’s Regulated Product Submission Table of Contents (RPS ToC) Pilot Program.
- Developed harmonized In-Vitro Diagnostic (IVD) and non-IVD Tables of Contents (ToCs) for premarket clearance or approval.
- Participating regulatory authorities : Australia (Therapeutic Goods Administration), Brazil (ANVISA), Canada (Health Canada), China (China Food and Drug Administration), and the European Union (Notified Bodies).
Summary : FDA’s collaborative efforts with ex-US Agencies to harmonize Device dossier formats for registrational submissions to accelerate global registration of devices
Addyi (flibanserin) (Sprout Pharmaceuticals, Raleigh, NC)
serotonin 1A receptor agonist and a serotonin 2A receptor antagonist
Indication: Generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:
- A co-existing medical or psychiatric condition,
- Problems within the relationship, or
- The effects of a medication or other drug substance.
- Three 24week, randomized, double-blind, placebo-controlled trials (Studies 1, 2, and 3).
- co-primary efficacy endpoints, one for satisfying sexual events (SSEs) and the other for sexual desire:
- Number of satisfying sexual events (per 28 days), P<0.01 – p<0.0001
- Desire (measured by e-Diary), Female Sexual Function Index, Female Sexual Distress Scale-Revised
- About 10 percent more Addyi-treated patients than placebo-treated patients reported meaningful improvements in satisfying sexual events, sexual desire or distress
Safety: Boxed warning and REMS
- Severely low blood pressure (hypotension) and loss of consciousness (syncope).
- Risks increased and more severe when patients drink alcohol or take Addyi with moderate or strong CYP3A4 inhibitors
- BOXED WARNING : Risks of severe hypotension and syncope in patients who drink alcohol during treatment with Addyi, in those who also use moderate or strong CYP3A4 inhibitors, and in those who have liver impairment
Stringent Risk Evaluation and Mitigation Strategy (REMS) – Elements to Assure Safe Use (ETASU)
Certification of HCPs, Pharmacy enrollment tracking
Mitigate the increased risk of hypotension and syncope due to an interaction with alcohol by:
- Ensuring prescribers and pharmacists are educate and need to counsel patients about this risk.
- Informing patients of the increased risk
Approval viewed as controversial with high probabilities of off-label use and unanticipated safety issues vs. unmet need and effectiveness. FDA’s proposed mitigation by Boxed Warning and stringent (REMS)
FDA ‘s approval part of Patient-Focused Drug Development – scientific workshop on female sexual dysfunction on October 27 and October 28, 2014, to solicit patient perspectives