Market Exclusivity Provisions Under US

Another "hot topic'' associated with product approvals is market exclusivity (statutory protection from competition in the form of generic copies). Market exclusivity terms (time period allocations) for registered drugs are linked to U.S. patent status. When a new chemical entity is first approved for marketing in the United States, its developer has the option to apply for a "term restoration'' to be granted on the basic product patent to extend its commercial life by adjusting the patent expiration date. Term extensions restore a portion of the time elapsed during the regulatory testing and review stage, but cannot exceed five years beyond the original patent expiration date. In addition to possible "restoration" days, several other factors must be taken into account when trying to determine precise dates of patent expiration. Refer to Chapter 10, "Intellectual Property,'' for further information and sources of pharmaceutical patent and trademark data.

The FDA is also empowered to grant market exclusivity, based on "novelty" criteria, independent of a product's patent status. For example, NCEs automatically earn five years of exclusivity. SNDAs for new indications or formulations of NCEs can be awarded three years of exclusivity. Officially designated "orphan" drugs, designed to treat or prevent relatively rare conditions that affect fewer than 200,000 U.S. citizens, are granted seven years of market exclusivity. New pediatric drugs earn six-month extensions to exclusivity terms. Former prescription-only drugs newly approved for OTC use (for which supplementary clinical evidence is required) can be granted three years of additional protection from generic competition. Exclusivity determinations by the FDA may exceed the patent term (i.e., extend beyond the expiration date of intellectual property protection). Original patent expiration dates and FDA market exclusivity terms are available in a source popularly known as The Orange Book.


Electronic Orange Book. 1938- . FDA. Monthly. URL: http:// The Orange Book is a cumulative list of all new drugs approved since 1938 in the United States, when the Food, Drug, Cosmetic Act set the stage for the premarket clearance process previously described in the introductory overview. Its official title, Approved Drug Products with Therapeutic Equivalence Evaluations, indicates that the primary purpose of this compilation is to provide bioequivalence data on multisourced products. The substitution of generic drugs for brand name products is governed at the state, rather than federal, level in the United States. Each of the 50 states has enacted laws governing product selection based on a state formulary. Each state's formulary identifies drugs authorized for substitution when dispensed in retail pharmacies. Typically, only those products listed in these substitution formularies are eligible for reimbursement under government-subsidized healthcare programs, such as Medicaid.

Individual hospitals, purchasing consortia, and health insurance (managed care) programs may also develop their own formularies of drugs eligible for generic substitution and/ or full or partial reimbursement. Neither state nor other private formularies can mandate generic substitutions for brand name products unless the generic drugs have an "A" (positive) bioequi-valence rating from the FDA. These ratings are listed in The Orange Book. On the other hand, states and other organizations can choose not to accept all Orange Book-rated bioequivalents as legally acceptable substitutes in their own formularies.

From a commercial standpoint, The Orange Book is significant in two ways: (1) it identifies generic competitors (if any) for branded products in the United States, and (2) it provides market exclusivity and patent expiration data associated with new drug approvals. Both of these factors are important in assessing company and product vulnerability.

The FDA web site offers only one of several versions of The Orange Book (others are cited below). The database found at the URL above is updated monthly, although the lag time in posting new drug approvals often extends beyond one month. Newly approved generic product listings are updated daily, as is new patent information. The FDA's interface enables searching by active ingredient (nonproprietary name), brand (proprietary) name, applicant (company), application number, or U.S. patent number. Search forms linked to each of these options prompt users to limit their queries to one ofthree lists: prescription drugs only, nonprescription drugs, or discontinued products. Search results, initially displayed in tabular format, identify active ingredients of products retrieved, as well as dosage form, route of administration, strength, brand name, and company.

Application numbers, also displayed in results tables, link to brief product information summaries that also indicate marketing status (Rx, OTC, or Discontinued) and approval date. A further link to patent and exclusivity data is available for NDA products. Patent information includes the United States patent number cited by the company in its original application and its original expiration date (caution: this date does not take into account possible extensions resulting from "term restoration'' decisions). The type of FDA-granted market exclusivity information (if currently applicable) is also provided (e.g., NCE, pediatric, and orphan drug), in addition to the exclusivity expiration date. Once patent or other exclusivity dates have expired, the FDA's Electronic Orange Book no longer displays these data elements.

The Electronic Orange Book home page also provides access to a separate list of approved orphan drugs and, under its Preface link, a downloadable PDF version of cumulative patent and exclusivity lists and updates.

Orange Book Companion™. URL: http://www.orangebook Using patent and market exclusivity data extracted from the FDA's Electronic Orange Book as a baseline, this publication provides subscribers with separate, precon-structed product tables organized by trade name, nonproprie-tary name, company name, drug class (per the U.S. National Drug Code system), and expiration date. The Companion also enhances The Orange Book data by adding titles of each patent cited, with hyperlinks to their full text. The database is available in CD/ROM or Web-based electronic format.

DIOGENES®: FDA Regulatory Updates. 1976- . Gaithers-burg, MD: FOI Services. Weekly. DIOGENES offers access to a huge and diverse collection of FDA regulatory documents related to human drugs and medical devices. Information published in the FDA's Orange Book is accessible in a separate subfile, providing a complete, cumulative list of drugs approved for marketing in the United States from 1938 forward, updated quarterly. Users can search drug approval records by brand or nonproprietary product names, applicant company name, and NDA application number. In addition,

DIOGENES offers many more search capabilities, enabling compilation of Orange Book entries for specified time periods, such as approval year/month date ranges, patent expiration dates, and market exclusivity dates. Other extra delimiters for retrieving Orange Book data in DIOGENES include approval type (NDA, SNDA, ANDA, and Abbreviated Biological), dosage form strength, and reason for market exclusivity. Options for searching the latter include the ability to isolate entries for NCEs, new esters or salts, new dosage forms, new route ofadministration, new strength, new patient population, and pediatric or orphan drug exclusivity. Another difference in DIOGENES' implementation of The Orange Book is that patent and exclusivity data are retained after expiration.

DIOGENES also provides access to many other FDA regulatory documents related to quality control and standards for good manufacturing or laboratory practices. These will be discussed in greater detail later in this chapter.


Drugs Under Patent. 1989- . Gaithersburg, MD: FOI Services Annual. This hardcopy reference book provides an annual, cumulative list of drugs under patent, based on NDA and SNDA patent references published in the previous year's Orange Book. Typically covering more than 2500 products, the list is conveniently cross-referenced through several separate indexes: company, brand name, nonproprietary name, dosage form, NDA number, exclusivity code, patent number, and patent expiration date.

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