505(b)(2) is more than a regulatory pathway — it’s a unique strategy that often can result in product approval with lower risk, reduced development cost, faster time to market and — perhaps most importantly — some period of market exclusivity. But while the 505(b)(2) process may offer advantages, it can pose significant challenges to those who are uninformed of its nuances. Before you can determine if your candidate is (b)(2) ready, you must understand what (b)(2) is and isn’t.
 
In broad terms, 505(b)(1), 505(b)(2) and 505(j) development pathways both seek to achieve a marketable product and must meet similar Food and Drug Administration (FDA) requirements. Generally, (b)(1) development is used when the drug under consideration is a completely novel therapeutic approach; (b)(2) development is employed when an approved drug is used as a jumping-off point to create a new product; and 505(j) is utilized to create a generic version of a branded product.
 
Here’s an easy way to compare the three options:
 

Regulatory Pathway	505(b)(2) NDA NDA that contains full safety and effectiveness reports, but allows at least some of the information required for approval to come from studies not conducted by or for the applicant	505(b)(1) NDA Full application — data predominantly obtained from studies conducted by the sponsor	505(j) ANDAAppropriate for generic drug products that are the same as approved (innovator) drug products
Required Scientific Studies	Partial, can use existing information in lieu of safety and efficacy studies	All safety and efficacy	Bioequivalence
Novel Active Moiety	✓	✓
New Indication	✓	✓
New Dosage Form (route of administration, regimen, etc.)	✓	✓	Limited
New Strength	✓	✓
Patent Eligibility	✓	✓	Maybe
Market Exclusivity	✓	✓
Development Time
Discovery	<1-3 years	2-5 years
Preclinical Studies	<1-2 years	1-3 years
Clinical Studies	2-5 years	5-8 years

 
Regardless of the regulatory pathway one chooses for an NDA, the FDA standards for the demonstration of efficacy and safety are the same; it is only the source of information that differs. Because drugs approved under 505(b)(2) can rely in part on data from existing reference drugs, products can be developed and achieve FDA approval in as little as 30 months with only a fraction the number of required clinical trials. However, successful use of this pathway requires working with an industry expert that understands what constitutes sufficient evidence and therefore which specific studies can be replaced by existing data.
 
In 2012, approximately 50 percent more products were approved through 505(b)(2) development as 505(b)(1); within the next few years, that percentage is expected to reach more than 80 percent. This increase is due in part to the fact that the 505(b)(2) pathway can be applied to pharmaceuticals in a wide range of development scenarios, including:

• New indications
• Changes in dosage form, strength, formulation, dosing regimen or route of administration
• New molecular entities (new active ingredients)
• Prodrugs of approved drugs
• DESI drugs
• Branded generics
• Orphan drugs
• Drug-device combination products

 
“Super Generics,” “Branded Generics,” “New Therapeutic Entities” and “Hybrids” are names used to describe products approved under the 505(b)(2) pathway or Europe’s hybrid procedure. (While similar, the hybrid procedure encompasses some situations that would require an abbreviated new drug application (ANDA) in the U.S. as well as a clinical endpoint study.)
 
However, it would be wrong to conclude that the 505(b)(2) pathway is only for changes in U.S. approved new drugs that are off patent. The 505(b)(2) pathway can and has been used to gain approval of drugs that have never been approved in the U.S., such as DESI drugs, new molecular entities and drugs either approved or in development in other countries.
 
Bringing a modified version of an existing drug to market through 505(b)(2), although potentially much faster and less costly than starting with a new compound, is still a demanding process requiring a thorough understanding of the FDA’s requirements. For many, 505(b)(2) offers a clear path to approval, a differentiated product, and at least some period of market exclusivity. The rising tide of drugs approved under this strategy is testament to its growing importance in the drug development market.