Definition
505(b)(2) is an FDA drug approval pathway that allows sponsors to submit a New Drug Application (NDA) while relying on published literature or FDA’s prior findings of safety and effectiveness for a previously approved drug, rather than conducting all required studies themselves. This hybrid approach accelerates development for modified versions of existing drugs.
How 505(b)(2) Works
The 505(b)(2) pathway was established by the Hatch-Waxman Amendments of 1984 to bridge the gap between full NDAs and generic ANDAs. Sponsors reference an approved Reference Listed Drug (RLD) and supplement with their own bridging studies to demonstrate the modification is safe and effective.
Key Requirements
- Identification of a suitable Reference Listed Drug (RLD)
- Bridging studies demonstrating bioequivalence or clinical equivalence
- Full chemistry, manufacturing, and controls (CMC) documentation
- Safety data for any new aspects of the formulation
- Patent certifications for the RLD
Benefits of 505(b)(2)
The pathway offers significant advantages for drug developers:
- Reduced Clinical Requirements: Leverage existing safety and efficacy data from the RLD
- Faster Development Timeline: Typically 3-5 years shorter than traditional 505(b)(1)
- Lower Development Costs: Fewer clinical trials mean reduced investment
- Market Exclusivity: Eligible for 3-year exclusivity for new clinical investigations
- Lifecycle Management: Extend product value through reformulations
505(b)(2) vs 505(b)(1) vs ANDA
| Aspect | 505(b)(2) | 505(b)(1) | ANDA |
|---|---|---|---|
| Purpose | Modified drug products | New molecular entities | Generic copies |
| Data Source | Own + referenced data | All original data | Bioequivalence only |
| Timeline | 3-5 years | 7-12 years | 2-3 years |
| Exclusivity | 3 years possible | 5 years NCE | None |
| Best For | New formulations, combinations | Novel drugs | Exact generics |
Recent 505(b)(2) Approvals
| Drug | Company | Approval Date | Indication |
|---|---|---|---|
| Leqembi (lecanemab-irmb) | Eisai/Biogen | Jan 2023 | Alzheimer’s disease |
| Rybelsus (semaglutide) | Novo Nordisk | Sep 2019 | Type 2 diabetes (oral GLP-1) |
| Austedo (deutetrabenazine) | Teva | Apr 2017 | Huntington’s chorea |
Data from PharmaDB regulatory database
Why BD Teams Track 505(b)(2)
For business development professionals, 505(b)(2) filings signal strategic lifecycle management opportunities:
- Deal Implication: Companies with 505(b)(2) programs often seek licensing partners with complementary formulation expertise or commercial reach
- Due Diligence Focus: Evaluate the strength of the bridge to the RLD and patent landscape complexity
- Opportunity Signal: Active 505(b)(2) programs indicate a company’s focus on capital-efficient drug development