What Is a 505(b)(2)?

Brian Bollwage, JD

Vice President, Regulatory Affairs

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IntroductionIn the U.S., Congress created the generic drug industry with passage of the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman) in 1984. This piece of legislation changed the face of the pharmaceutical marketplace in the U.S. forever, resulting in a market today where more than 80 percent of new prescriptions are fulfilled with generic versions of the prescribed drug product. Congress’ simple intent in drafting Hatch-Waxman, signed into law by President Reagan, was to reduce the cost of prescription drugs to consumers — an objective that has certainly been realized.

However, Congress also intended with this legislation to encourage further innovation for drugs that have already received approval from the U.S. Food and Drug Administration (FDA). Section 505(b)(2) of the Food, Drug and Cosmetic Act, as created under Hatch-Waxman, permits submission of a new drug application (NDA) containing one or more investigations necessary to approval that were not conducted by the applicant and for which the applicant has no right of reference.

Does this mean that a new sponsor can rely upon work done by a prior sponsor in submitting a new NDA application? Yes, that is exactly what it means. The new or improved version of the drug must be different in some respect from the innovator version in order to qualify under 505(b)(2). If the new drug is merely a bioequivalent version of the originator’s drug, then this would be considered a generic drug and would not fall under the provisions of 505(b)(2).

Innovations that may qualify for 505(b)(2) treatment include modifications to the dosage form, formulation, strength, route of administration, dosing regimen, indication for use, active ingredient and others. Reliance on the predecessor’s data may include both nonclinical and clinical studies; even the scientific literature may be used. Section 505(b)(2) also provides for potential approval exclusivity of three to five years if clinical trial data is a requirement for approval. If a 505(b)(2) qualifies for orphan drug designation, the award of exclusivity may be as much as seven years.

How Does 505(b)(2) Work?The standard for approval of a 505(b)(2) NDA application is the same as a traditional NDA. Both applications require inclusion of data demonstrating substantial evidence of safety and effectiveness. However, the source of the data may be very different. In a traditional NDA, you own all the data. In a 505(b)(2) NDA, you rely upon data that you don’t own or have a right of reference to, including published literature. For example, you can rely on general, non-product-specific published literature or the FDA’s previous finding of safety and effectiveness (i.e., previous NDA approval).

In order to leverage this data, the 505(b)(2) sponsor needs to build a bridge back to the approved product, which may require bioavailability, bioequivalence or efficacy trials, for example. The requirements for this bridge will be different depending upon the unique circumstances of the product being developed; therefore, each bridge will need to be designed in a customized fashion. No “bridge in the box” approach would be expected to satisfy each and every project.

Contents

2 Introduction

2 How Does 505(b)(2) Work?

3 The Pre-IND Meeting

3 Conclusion

This piece of legislation changed the face of the pharmaceutical marketplace in the U.S. forever, resulting in a market today where more than 80 percent of new prescriptions are fulfilled with generic versions of the prescribed drug product.

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Sponsors can begin to navigate the 505(b)(2) process by researching available FDA guidances and performing a thorough literature search on the active ingredient. While data leveraging should be considered an opportunity, it needs to be realistically balanced against the data gaps that are identified after performing an NDA suitability review. It pays to be optimistic but optimism should be tempered with a realistic assessment of the probability of success. This is best accomplished by developing a realistic plan to support the usefulness of your product innovation and convening a meeting with the relevant FDA review division to validate your 505(b)(2) development plan.

The Pre-IND Meeting Establishing a dialogue with the FDA is critical to the success of any 505(b)(2) development plan. In a mere 10 weeks’ time, a sponsor can build the necessary foundation to ensure a successful development pathway. First and most important is the need to confirm that 505(b)(2) is a suitable path. The FDA can and will refuse to file an NDA for a drug that is a duplicate and therefore eligible for approval as an abbreviated new drug application (505(j) or ANDA).

During pre-IND discussions, sponsors can also establish the product’s value and define the target label. FDA buy-in to the proposed development strategy or FDA input into the plan can save time and money and significantly accelerate the development process. Additionally, any significant objections can be identified and addressed, thereby facilitating development or making any no-go decisions much more apparent.

Conclusion The 505(b)(2) NDA provides a potentially streamlined path for sponsors that have developed improvements to drug products that have previously received FDA approval. Successful navigation of the process requires close communication with the FDA but the potential benefits can be significant.

About ChilternChiltern is the leading, global mid-sized contract research organization that listens to client needs to deliver customized clinical development solutions. Chiltern’s team of more than 4,000 works across 47 countries to provide comprehensive, yet flexible and responsive, services with specialties in Biopharma, Medical Device & Diagnostics, Oncology, Clinical Analytics and Source. Visit Chiltern.com to learn more about solutions that are Designed Around You®.

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