What is the difference between NDA vs ANDA vs Orphan Drugs

NDA vs ANDA vs 505(b)(1) vs 505(b)(2) vs Orphan Drug in USFDA

NDA vs ANDA vs Orphan Drugs: Understanding which USFDA drug application pathway best fits your product is key to market success. This article compares NDA (505(b)(1)), ANDA, 505(b)(2), and Orphan Drug Designation, with examples of real-world formulations and clarification on PDUFA vs GDUFA fees.

1. NDA (505(b)(1)) – New Drug Application

The 505(b)(1) route requires full submission of preclinical and clinical data for novel molecules.

💰 Fee Type: PDUFA

Subject to PDUFA (Prescription Drug User Fee Act) fees. Estimated cost in FY2025 is ~$4 million for applications requiring clinical data.

Drug	Brand	Company	Formulation	Indication
Osimertinib	Tagrisso	AstraZeneca	Oral Tablet	NSCLC
Upadacitinib	Rinvoq	AbbVie	ER Tablet	Rheumatoid Arthritis
Lurasidone	Latuda	Sumitomo Pharma	Film-coated Tab	Schizophrenia

2. ANDA – Abbreviated New Drug Application

Used for generic versions of approved drugs demonstrating bioequivalence.

💰 Fee Type: GDUFA

Subject to GDUFA (Generic Drug User Fee Amendments) fees. FY2025 filing fee is approximately $240,000.

Generic Drug	Brand (RLD)	Company	Formulation
Atorvastatin	Lipitor	Teva, Aurobindo	Oral Tablet
Metformin	Glucophage	Sun Pharma	Oral Tablet
Omeprazole	Prilosec	Dr. Reddy’s	Delayed-release Capsule

3. 505(b)(2) – Hybrid NDA

Used when sponsors rely partly on published data or previous approvals, plus new bridging studies.

💰 Fee Type: PDUFA

Same fee structure as 505(b)(1), governed by PDUFA.

Drug	Brand	Company	Modification
Treximet	Treximet	Pernix Therapeutics	Combo of Sumatriptan + Naproxen
Dextenza	Dextenza	Ocular Therapeutix	New ophthalmic insert
DepoSubQ Provera	Depo-SubQ	Pfizer	New route: SC injection

4. Orphan Drug Designation

A special status granted for drugs treating rare diseases (≤200,000 patients/year in the U.S.). Applied alongside NDA or 505(b)(2).

💰 Fee Type: PDUFA (Often Waived)

PDUFA fees are waived if the sponsor qualifies. Includes 7 years exclusivity and clinical tax credits.

Drug	Brand	Company	Indication
Spinraza	Spinraza	Biogen	Spinal muscular atrophy
Zolgensma	Zolgensma	Novartis	Gene therapy for SMA
Trikafta	Trikafta	Vertex	Cystic Fibrosis (CFTR mutation)

🔍 Comparison Table with Fee Type

Feature	NDA 505(b)(1)	ANDA	505(b)(2)	Orphan Drug
Drug Type	New entity	Generic copy	Modified or repurposed	Rare disease drug
Clinical Trials	Full (Phases I–III)	No	Partial	Varies
Fee Type	PDUFA	GDUFA	PDUFA	PDUFA (waived)
Market Exclusivity	5 years	180 days (first)	3–5 years	7 years
Cost & Time	High	Low	Medium	Medium to High

Keywords:

FDA PDUFA vs GDUFA
505(b)(1) vs 505(b)(2) difference
Orphan drug designation benefits FDA
ANDA vs NDA FDA approval
Difference between NDA vs ANDA vs Orphan Drugs
USFDA drug approval process chart