Potential Data and Market Exclusivity Granted During the U.S. Regulatory Approval Process

There are 3 potential regulatory approval pathways that new drug products must go through in order to receive approval in the United States, including 505(B)(1) or NDA, 505(B)(2), and 505(J) or ANDA. This process is costly and arduous. As a method of compensation and motivation to develop new medications, the FDA offers multiple data and market exclusivity periods. Utilizing these strategies is essential to drug development and commercialization. Other articles cover data and market exclusivities that go along with new product applications as well as the regulatory approval pathways.


Companies looking to bring new drug products to market in the United States must go through any one of the major potential regulatory approval pathways:


● 505(b)(1) (commonly referred to as new drug application, or NDA)

● 505(b)(2)

● ANDA (abbreviated new drug application)


However, no matter what regulatory approval pathway a company decides to pursue, getting a new product to market is an arduous journey. The discovery and development process is lengthy and expensive—the entire development process can last between 10–15 years with costs approaching $2.6B—and the clinical success rate (percentage of products approved by the FDA) for all products sits between just 9% and 14%.


As a way to compensate innovator companies facing these challenges, the FDA provides various drug exclusivity periods during which an innovator company has a certain time frame of exclusivity on the market. These data and market exclusivities include:


Data and Marketing Exclusivities

New Chemical Entity (NCE) Exclusivity and Patent Term Extensions


Eligibility

The NDA must be for a drug that includes an active moiety that has never been approved in the United States.


Exclusivity

Under NCE exclusivity, an ANDA or 505(b)(2) new drug application cannot be filed by anyone until 4 years after the NDA’s approval, and the FDA cannot approve an ANDA or 505(b)(2) application until 5 years after the NDA’s approval.


When a company files an NDA seeking approval of a drug that includes an active ingredient that has never been approved in the United States, usually it is entitled to a Patent Term Extension (PTE). Companies usually have more than one patent covering their drug product.


The PTE can only be applied to 1 of these patents. PTEs can extend the term (the time until expiration) of the patent up to 5 years, but there is a limit to this. PTEs may not extend the term of a patent beyond 14 years after an NDA’s approval.


New Product (NP)/Clinical Study Exclusivity


Eligibility

The application must be for a drug product that contains an active ingredient that has been previously approved but contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the applicant that were essential to approval of the application.


For example, changes in an approved drug product that affect its active ingredient(s), strength, dosage form, route of administration, or conditions of use may be granted exclusivity if clinical investigations were essential to approval of the application containing those changes. It is important to note that NP exclusivity only protects the changes, it does not protect the drug product for the original chemical entity.


Exclusivity

Under NP exclusivity, a product has 3 years of market exclusivity.


NP exclusivity does not prevent the filing of ANDA or 505(b)(2) applications, but the FDA cannot grant effective approval to an ANDA or 505(b)(2) until after the expiration of the NP exclusivity.


Orphan Drug Exclusivity (ODE)


Eligibility

The application must be for a drug product developed for treatment, diagnosis, or prevention of rare disease/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 people but is not expected to recover the costs of drug development and marketing.


Exclusivity

Under ODE, a product has 7 years of market exclusivity.

For a drug product with multiple approved indications, the exclusivity protects only the orphan drug indication. Accordingly, a drug approved for an additional non-orphan indication may be subject to a generic drug label “carve out" of the protected orphan indication in an ANDA’s label.


For example, Abilify is an atypical antipsychotic indicated for multiple conditions, including the treatment of schizophrenia and Tourette’s Disorder. In December 2014, the FDA granted ODE for the Tourette’s Disorder indication, which means that the FDA cannot approve generic versions of Abilify labelled for Tourette’s Disorder until after the ODE expires in December 2021. In the meantime, however, the FDA has approved generic versions of Abilify that omit (or “carve out”) the protected orphan indication for Tourette’s Disorder in the label.


Pediatric Exclusivity


Eligibility

In some instances, the FDA may issue a written request for the brand company to conduct pediatric studies of a drug. If the brand company performs the pediatric studies in accordance with FDA’s request, then patents covering the branded drug may be eligible to receive pediatric exclusivity. If an applicant wants to become eligible for pediatric exclusivity, the applicant may submit a proposal asking FDA to issue a written request. FDA will review the proposal and determine whether to issue a written request.


Exclusivity

If the brand company performs the pediatric studies in accordance with the FDA’s request, then patents covering the branded drugs may be eligible to receive an additional 6 months of pediatric exclusivity. A 6‐month pediatric exclusivity that attaches after a patent term is not a patent extension; it is an FDA‐enforced exclusivity period that begins at the termination of the patent.


Qualifying Infectious Disease Products


Eligibility

Under the 2012 Generating Antibiotics Incentives Now (GAIN) Act, a company may qualify for this exclusivity if it develops an antibiotic intended for a “qualified infectious disease.” The GAIN Act fails to describe which diseases are “qualified,” but the FDA released a list of pathogens that, if targeted by a product, would qualify the product for the additional marketing exclusivity.


Exclusivity

A qualifying infectious disease product gains an additional five years of marketing exclusivity.


Automatic 30-Month Stay


Eligibility

An ANDA or 505(b)(2) filer may seek effective approval of its application before the expiration of Orange Book‐listed patents by submitting an ANDA Paragraph IV certification stating that the patents are invalid, unenforceable, or would not be infringed by its proposed generic product.


Exclusivity

If an NDA holder sues an ANDA or 505(b)(2) filer for patent infringement within 45 days after receiving formal notification of the Paragraph IV certification, then the lawsuit triggers a 30‐month stay on FDA’s authority to grant effective approval to the ANDA or 505(b)(2).

In situations where the branded drug enjoys NCE exclusivity, the 30‐month stay attaches to the end of the NCE exclusivity, such that FDA cannot grant effective approval to the ANDA or 505(b)(2) until 30 months after the expiration of the NCE exclusivity (in total, 7.5 years after the branded drug gained approval).


In situations where the branded drug does not enjoy NCE exclusivity, the 30‐month stay begins to run from the date on which formal notification was received. Certain court decisions may result in an early termination of the 30‐month stay, including for example, a district court decision that the patent is invalid or not infringed.


180-Day Exclusivity


Eligibility

180-day exclusivity is available in the ANDA pathway only; a 505(b)(2) filer does not qualify for 180‐day market exclusivity.


Exclusivity

The first applicant that submits and maintains an ANDA with a Paragraph IV certification against an Orange Book‐listed patent may receive 180‐day marketing exclusivity that begins upon marketing by any first applicant. The 180‐day exclusivity prevents FDA from granting effective approval to subsequent ANDAs. Exclusivity is available on a product‐by‐product basis. There can be more than one “first applicant” if multiple ANDAs are filed on the same day, or if different ANDAs are filed on different days for different dosage forms or different strengths.


The 180‐day exclusivity can be forfeited by the first applicant in six distinct ways: