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Strong PK Development Plan with 505(b)(2) Strategy

Many pharmaceutical scientists involved in drug development understand the challenges and opportunities associated with the 505(b)(2) regulatory approval process. However, in an effort to advance a 505(b)(2) technology rapidly and at minimal cost, even the most seasoned researcher can be left wondering at the end of the registration process:

“What could we have done differently to better differentiate our product? Or worse. What went wrong?”

The answer to both parts of this lingering question often resides in having a strong Pharmacokinetic (PK) Development Plan – one that minimizes risk, maximizes value, and is both understandable and agreeable to FDA at program initiation. While there are numerous examples of changes to existing drugs for which the 505(b)(2) pathway would apply, specific examples that often benefit from a strong PK development plan include:

  • Altering the release kinetics of the existing formulation
  • Changing the route of administration
  • Finding a new indication
  • Altering the dose on the basis of the existing drug’s pharmacokinetic (PK) and pharmacodynamics (PD) profile
  • Combining drugs to enhance efficacy and/or improve safety
  •  Imparting a different characteristic to an existing product, such as abuse deterrence.

For many oral products utilizing the 505(b)(2) approval process, the minimum PK requirements can be met by conducting studies to address issues related to bioequivalence/bioavailability, food effect, and multiple-dose PK (for modified-release formulations).

However, with a complete understanding of the PK disposition of the existing drug and the new approach being investigated, any 505(b)(2) program can become strengthened by optimizing the formulation and dosing strategy as early as possible in the program, predicting the results of differentiating studies, and communicating the strategy more effectively to regulatory authorities at every phase in development.

Often this can be accomplished through effective PK/PD modeling and simulation and applying basic biopharmaceutics principles as part of a model-based approach to drug development. Or, as many PK researchers with 505(b)(2) experience have come to realize when there is a wealth of PK data on the existing drug: “Six hours in front of the computer can often save a company six months of trial and error!”

No doubt, the 505(b)(2) approval pathway can provide a pharmaceutical company with an opportunity to empower their pipeline by reducing cost, risk, and time by not having to establish the safety and efficacy for a New Chemical Entity (NCE).

In fact, a well-defined 505(b)(2) program can often save 1-2 years of preclinical research and 5-10 years of clinical research, with some programs often proceeding directly from Phase 1 to Phase 3 if the PK/PD profile of the existing drug is already known. In addition, the 505(b)(2) product can have even greater commercial potential than the existing drug if the new product can be differentiated in a favorable way, including a patent.

Experience has shown that a 505(b)(2) application that has no meaningful differentiating qualities between itself and the existing drug, other than its increased complexity, has the potential to become weighed down with as many regulatory obstacles as an NCE. At Nuventra, we are committed to applying all of our PK/PD/TK and Biopharmaceutical skills to the successful development of both new drug entities (e.g., NCEs) and 505(b)(2) drugs in the US and Europe.


Contact one of Nuventra’s consultants to better understand how Nuventra can help empower your 505(b)(2) pipeline a with strong PK development plan.

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