Introduction

Innovator (brand-name) drug companies spend millions of dollars to develop a single, new innovator drug. It is therefore understandable that they would want competing drugs to remain off the market as long as possible. Many innovator drug companies have thus developed strategies to delay the appearance of generic drugs on the market. One of these strategies is to obtain a patent for an innovator drug’s elements to assure safe use (ETASU) program.

Background

The FDAAA, REMS, and ETASU

The Food and Drug Administration Amendments Act (FDAAA) of 2007 gave the FDA the authority to require drug companies to develop a risk evaluation and mitigation strategy (REMS) for certain drugs. A REMS is a set of actions designed to “manage a known or potential serious risk associated with a drug” and thus improve the safety of the drug. The FDA can require a REMS for any drug for which it feels that a REMS is “necessary to ensure that the benefits of the drug outweigh [its] risks.”

The components of a REMS are outlined in the FDAAA of 2007. They include a mandatory assessment plan to evaluate the REMS’s effectiveness, plus at least one of the following: medication guides, plans for communications with healthcare providers, and elements to assure safe use (ETASU). The ETASU consist of six actions, which may be used alone or in combination. They include such requirements as special training for prescribers or dispensers of the drug and specific monitoring of patients receiving the drug.

ETASU and Generic Drugs

According to the FDAAA of 2007 , if the FDA decides that an innovator drug requires a REMS, then its generic counterpart must also have a REMS. Furthermore, if the innovator drug’s REMS includes any ETASU, then the generic drug company will generally be expected to use the same ETASU, so that all similar drugs use a “single, shared [ETASU] system.”

ETASU and Patents

An innovator drug company can obtain a patent for its ETASU program if the ETASU meets three criteria: new, useful, and non-obvious. The “new” and “useful” criteria are easy to meet, as ETASU programs originated only a few years ago and their goal of improving drug safety is certainly useful. “Non-obvious” is more challenging, as it means that the ETASU program cannot be a simple variation or combination of existing ETASU programs. By obtaining a patent for its ETASU program, an innovator drug company prevents a generic drug company from using its ETASU program without permission for 20 years after the date the patent application was submitted.

Issue

Do patented ETASU programs have the potential to delay generic drugs from coming onto the market?

Rules

Patented ETASU programs have the potential to delay generic drugs from coming onto the market if they cause a delay in either of the following:

1. The generic drug company’s application for marketing being submitted to the FDA

2. The generic drug company’s application for marketing being approved by the FDA

Analysis

Delay in the generic drug company’s application for marketing being submitted to the FDA

When applying to the FDA for marketing approval of a generic version of a previously FDA-approved innovator drug, the generic drug company submits an abbreviated new drug application (ANDA). The FDAAA of 2007 states that an ANDA must include the same ETASU as the innovator drug, unless these exceptions exist: 1.) the FDA decides that the disadvantages of having a single system shared by both the innovator and generic drug outweigh the advantages; or 2.) the ETASU program is patented and the generic drug company is unable to obtain a license from the innovator drug company to share its ETASU program.

Therefore, when an innovator drug company has a patented ETASU program, the generic drug company must negotiate with the innovator drug company to obtain a license to use its ETASU program. These negotiations can be a lengthy process, especially since the innovator drug company benefits by prolonging the negotiations as long as possible. If the innovator drug company finally agrees to share its ETASU program, the license can be very expensive. The high cost can cause a further delay in the generic drug company submitting an ANDA if it needs to acquire additional funds for the license. An expensive license may even cause the company to decide to abandon its plans to submit an ANDA.

If the generic and innovator drug companies fail to reach an agreement about a license during their negotiations, the FDAAA of 2007 states that the FDA may attempt to negotiate with the innovator drug company to allow the generic drug company to obtain a license; however, the FDA has no legal authority to require an innovator drug company to provide one. Negotiations between the FDA and innovator drug company would add to the delay in the generic drug company’s ANDA being submitted to the FDA. An even greater delay would occur if the innovator drug company ultimately refused to allow the generic drug company to share its ETASU program. In this situation, the generic drug company would be required to develop its own ETASU program, which the FDAAA of 2007 indicates must be “comparable” to the innovator drug’s ETASU program. This would certainly be time-consuming and it would also likely be expensive, which (like expensive licenses) may delay or even prevent the submission of an ANDA. Indeed, the time and expense may be particularly large because in order to meet the criteria for a patent, the innovator drug’s ETASU program will likely be at least moderately complicated. The patented ETASU program for ThalomidR known as the S.T.E.P.S.R program, for example, requires 175 workers to run it. Thus, a patented innovator drug ETASU program can lead to situations that delay the submission of a generic drug’s ANDA to the FDA.

Delay in the generic drug company’s application for marketing being approved by the FDA

Once an ANDA is finally submitted to the FDA, delays can also arise during the approval process if the ETASU program of the corresponding innovator drug is patented. For example, if the generic drug company develops its own ETASU program, the FDA must perform an evaluation to determine whether it is sufficiently similar to the innovator drug ETASU program to be considered “comparable,” but also sufficiently different so that it does not violate the patent. This evaluation will be a complicated process, which will likely be prolonged and involve multiple groups at the FDA.

As well, the innovator drug company may take direct action to try to prevent the FDA from approving the ANDA. For example, Celgene Corporation submitted a citizen’s petition to the FDA in September 2007 urging that no generic version of its innovator drug ThalomidR be approved. Celgene claimed that the safety of ThalomidR was critically dependent on its patented ETASU program (the S.T.E.P.S.R program), which contains elements to severely restrict the distribution of ThalomidR so the drug is used under only certain circumstances. Celgene stated that without an ETASU program equivalent to the S.T.E.P.S.R program (which it would not share), a generic version of ThalomidR would not be safe. Celgene further argued that if a generic drug company did develop its own ETASU program that the FDA considered to be adequate, then the existence of multiple ETASU programs would increase the likelihood of “confusion and medication errors,” such as those previously reported for isotretinoin when there used to be multiple versions of its risk management plan (the precursor to REMS). At the time of Celgene’s citizen’s petition, only one generic drug company, Barr Laboratories, had submitted an ANDA. The FDA delayed approving the ANDA and Barr eventually withdrew its ANDA in 2010. Therefore, a patented innovator drug ETASU program can lead to situations that delay approval of a generic drug’s ANDA by the FDA.

Conclusion

Patented ETASU programs have the potential to delay generic drugs from coming onto the market because they can delay the generic drug company’s application for marketing (ANDA) being submitted to the FDA and/or delay the generic drug company’s ANDA being approved by the FDA.

For more information about this issue, contact the Kulkarni Law Firm.