The 505(b)(2) pathway is one of the regulatory routes to approval under the FDA’s New Drug Application (NDA). The 505(b)(2) pathway can often lead to a faster route to approval when compared to traditional development pathways such as the 505(b)(1), which is a full NDA application for innovator drugs.
The 505(b)(2) is a streamlined process that enables investigators and/or manufacturers to apply for approval in the US without having to repeat all the drug development work done for the original, innovator drug. The 505(b)(2) is reserved for situations in which a modification (often an improvement) is being made to the innovator drug resulting in the creation of a whole new and differentiated “drug product” – with its own commercial value and exclusivity.
The 505(b)(2) can incorporate elements of an ANDA (505)(j) and a NDA 505(b)(1) and can be utilized for a variety of different marketing applications, including:
- Branded generics
- Drug Efficacy Study Implementation (DESI) Drugs
- Drug-device combinations
- Orphan Drugs
Advantages of the 505(b)(2) Regulatory Pathway
The 505(b)(2) strategy can be valuable to pharmaceutical companies for a variety of reasons. This pathway can alleviate some of the cost and time associated with the traditional full NDA. In addition, utilization of the 505(b)(2) pathway can eliminate the need for most nonclinical studies and extensive safety and efficacy tests.
A well-defined 505(b)(2) program can often save 1-2 years of pre-clinical research and 5-10 years of clinical research. Some programs can proceed directly from Phase 1 to Phase 3 if the PK/PD profile of the existing drug is already known. Major benefits may include:
- Potential of lower risk due to previous drug approval
- Faster development and lower cost due to fewer studies needed
- Potential to qualify for 3-7 years of market exclusivity
505(b)(2) Marketing Exclusivity
Once approved, 505(b)(2) applications are typically granted 3 years of Clinical Investigation Exclusivity (CIE), rather than the typical 5 years of exclusivity for an innovator product. This type of exclusivity is the most common type for 505(b)(2). However, it is important to understand that market exclusivity is not tied to the development pathway, which is a common misconception.
In fact, 505(b)(2) drugs can have longer or shorter exclusivity durations. There are examples where 505(b)(2) drugs have been granted new chemical entity (NCE) exclusivity, which provides 5 years of market exclusivity, or even orphan drug exclusivity, which provides 7 years of exclusivity.
505(b)(2) Development Strategies
When creating a 505(b)(2) development program, it is important to determine how the new drug product is different (and similar) to the innovator drug, especially in relation to its pharmacokinetics (PK) characteristics. From there, you can leverage all information relevant to the new drug product by creating a “PK bridge” linking the in vivo performance of the new drug product to that of the original/innovator drug product. Understanding how to best link the two products is an essential step in maximizing the full streamlining capability of the 505(b)(2) approach.
For 505(b)(2) oral products, the minimum PK requirements can often be met by conducting studies to address issues related to food effect, bioequivalence, bioavailability, and multiple-dose PK (for modified-release formulations). Nuventra can help develop your 505(b)(2) strategy by creating the strongest PK development plan possible for your program.
Nuventra’s 505(b)(2) Consulting Experience
Nuventra’s senior scientific staff has extensive experience supporting 505(b)(2) development programs from both a strategic and operational perspective. Our approach is to match regulatory knowledge with scientific, clinical, nonclinical, and overall drug development expertise to find the right path for each 505(b)(2) program.
Nuventra has been involved with dozens of 505(b)(2) programs. Some examples of 505(b)(2) services we have provided are listed below:
- Comparative BA with RLD
- Comprehensive strategic consulting
- FDA meetings
- Formulation performance studies
- New formulations, new indications, & new route of administrations
- Replacement for oral administration
- Support for IND and NDA
Contact Nuventra for 505(b)(2) Application Support
The 505(b)(2) development pathway provides far more efficient drug development for follow-on products and non-innovator drugs by allowing reliance on external data and previous investigations for the NDA application. Understanding how to “bridge” your new drug product to an approved drug and knowing what types of information are appropriate to use is critical to getting your drug approved through the 505(b)(2) regulatory pathway.
Contact one of our 505(b)(2) experts today for help with your development program.