FDA Issues Draft Guidance to Improve the Orange Book

By Patricia Van Arnum - DCAT Editorial Director

February 1, 2019

The US Food and Drug Administration (FDA) has issued draft guidance and outlined future guidances to improve the so-called Orange Book, officially known as the Approved Drug Products with Therapeutic Equivalence Evaluations Publication, which provides a list of drug products approved by the FDA under the Federal Food, Drug, and Cosmetic Act that includes patent and exclusivity information and identifies whether a drug is currently being marketed or has been discontinued.

"Given the important benefits of a modern, up-to-date Orange Book, today [January 30, 2019], we’re announcing several new steps the agency will be taking to ensure that the Orange Book provides the greatest benefit to patients and providers and generic-drug developers,” said FDA Commissioner Scott Gottlieb in a January 30, 2019 agency statement. “We want to make sure it provides as much utility as possible to aid manufacturers as they allocate resources towards the development of new generic drug products.”

The first of these actions is a new draft guidance, Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and Cosmetic Act; Content and Format. The draft guidance provides approved drug-application holders with clarity on the specific categories and descriptions of the information they’re required to share with FDA on the marketing status for their brand and generic drugs and how to provide it in a timely and consistent manner.

”Having timely, accurate information about what drugs are being actively marketed helps provide transparency around circumstances where generic competition is lacking,” said Gottlieb in the agency statement. “It helps us also better understand circumstances where generic medicines are being approved, but not marketed, so that we can better consider any policy reasons why this may be occurring."

The draft guidance stems from the FDA Reauthorization Act of 2017, which imposed additional reporting requirements on holders of new drug applications and abbreviated new drug applications regarding the marketing status of approved drug products, including: notification of a withdrawal from sale; notification of a drug not available for sale; and a one-time report on marketing status for actively marketed drugs. The draft guidance identifies the required content for marketing status notifications, the recommended format for submitting these notifications to the agency, and the required timelines for their submission. Gottlieb said that the agency will be taking other actions in the coming year to enhance the Orange Book and its processes. Specifically, he said the agency intends to issue draft guidance describing how the FDA evaluates therapeutic equivalence (TE) and assigns therapeutic equivalence codes, which are published in the Orange Book.

“We believe this guidance will increase transparency around the FDA’s policies and procedures related to evaluation and assignment of TE codes to support applicants submitting requests for therapeutic equivalence and help advance pathways for achieving pharmacy-level substitution of therapeutically equivalent drug products, including products approved under the 505(b)(2) pathway,” he said in the agency statement. A 505 (b)(2) new drug application is a pathway created by the Hatch-Waxman Amendments of 1984, with 505(b)(2) referring to a section of the Federal Food, Drug, and Cosmetic Act. It applies to various uses, including changes in dosage form, strength, route of administration, formulation, dosing regimen, or indication.

"We believe this will be particularly beneficial for those seeking to develop generic products for harder-to-copy complex drugs that often face greater scientific and regulatory challenges and thus often have less competition,” said Gottlieb in the agency statement. “For some of these drugs, the 505(b)(2) pathway may provide a more efficient development path, and the agency is developing policy for how manufacturers can acquire a therapeutic equivalence rating to allow for full substitutability for products developed by this route.”

Gottlieb also said that the agency plans to issue a draft guidance to assist drug-product applicants and approved application holders in using the Orange Book. “The guidance will provide answers to commonly asked questions that we have received from these interested parties regarding the Orange Book,” he said.

Separately, the agency will be soliciting public comment on Orange Book use and potential enhancements, including a re-examination of what pharmaceutical patents should be listed in the Orange Book. “For example, if a product has been approved for use in conjunction with a digital application, we plan to consider whether the drug-application holder should be required to list any patents associated with this digital application,” explained Gottlieb. “We want to hear from the public on the pros and cons of requiring patent listings in these and other circumstances. To take the case of the digital application, listing such patents could help generic developers to assess all intellectual property assertions related to the product that could potentially block generic entry and determine its approach to these patents. This could allow generic competitors to better assess which products they choose to develop and provide greater clarity as to the path to market."

Gottlieb said these measures to improve the utility of the Orange Book are part of a larger policy goal to facilitate generic-drug development, review, and approval as a means to increase drug competition, lower costs, and improve market access. “This is why, in addition to taking action to enhance generic competition, the FDA must work to make generic-drug development more efficient and predictable,” he said in the agency statement. “In addition to our work to reduce approval times and to enhance the efficiency of certain aspects of the submission process for generic-drug applicants, we are striving to provide the industry with increased transparency to provide greater certainty around timing of market entry and enable more informed decisions on how to prioritize their resources. The steps we’re taking in relation to the Orange Book are only one component of these transparency initiatives, and we look forward to continuing to provide updates on additional steps in the coming year."

Source: US Food and Drug Administration