Utilizing 505(b)(2) Regulatory Pathway for New Drug Applications: An Overview on the Advanced Formulation Approach and Challenges

Abstract

More than 50% of approved drugs on the market contain poorly water-soluble APIs, which typically are associated with poor bioavailability, suboptimal drug delivery, ineffective drug efficacy, and side effects. This creates a huge opportunity in generating 505(b)(2) products, which address unmet medical needs by applying formulation technologies to overcome those difficulties. A key feature of the 505(b)(2) pathway is the 505(b)(2) sponsor can rely upon clinical data or literature produced by other companies. The 505(b)(2) pathway allows manufacturers to acquire FDA approval without performing all the work required with a traditional NDA. The 505(b)(2) strategy can be an option to improve existing drug products with a new indication, dosage form, dosing regimen, strength, combination with other products, new route of administration, elimination of food effect, switching from a prescription drugs (Rx) to an over-the-counter (OTC), non-prescription product that differs from the OTC monograph, and orphan drug indications. Both generic and brand companies are turning to more complex 505(b)(2) products to avoid the commoditized generic competition. Revitalization of older marketed drug products using innovative drug delivery technologies or platforms can provide new marketing exclusivity and new patent protection, and thus offer an effective tool for product life cycle management.