FDA ORANGE BOOK
Additional information and resources for the Orange Book. We've updated our mobile app! Download Orange Book Express The publication Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book) identifies drug products approved. The publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book), identifies drug products.
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The electronic availability of the Orange Book brings this valuable tool to the web for healthcare professionals. FDA Drug Info Rounds pharmacists discuss how. Orange Book may refer to: Trusted Computer System Evaluation Criteria, a computer security standard; The Orange Book: Reclaiming Liberalism, by members of the British Liberal Democrat party; Approved Drug Products with Therapeutic Equivalence Evaluations, published by the FDA's Center for. The Drug Price and Competition Act (Hatch-Waxman Act) requires FDA to publish Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. The Orange Book identifies drug products approved on the basis of safety.
In addition, the Orange Book contains therapeutic equivalence evaluations for approved multisource prescription drug products. These evaluations have been prepared to serve as public information and advice to state health agencies, prescribers, and pharmacists to promote public education in the area of drug product selection and to foster containment of health care costs. Background of the Publication. These state laws generally require either that substitution be limited to drugs on a specific list the positive formulary approach or that it be permitted for all drugs except those prohibited by a particular list the negative formulary approach.
Because of the number of requests in the late s for FDA assistance in preparing both positive and negative formularies, it became apparent that FDA could not serve the needs of each state on an individual basis.
The Agency also recognized that providing a single list based on common criteria would be preferable to evaluating drug products on the basis of differing definitions and criteria in various state laws.
The Orange Book was distributed as a proposal in January These evaluations are presented in the form of code letters that indicate the basis for the evaluation made. An explanation of the codes appears in the Introduction.
The final rule, which includes FDA's responses to the public comments on the proposal, was published in the Federal Register on October 31, 45 FR The first publication of the Orange Book in October , concurrent with finalization of the rule, incorporated appropriate corrections and additions.
Each subsequent edition has included new approvals and made appropriate changes in data. The Hatch-Waxman Amendments require that FDA, among other things, make publicly available a list of approved drug products with monthly supplements. The Orange Book and its monthly Cumulative Supplements satisfy this requirement. The Agency intends to use this publication to further its objective of obtaining input and comment on the publication itself and related Agency procedures.
Comments received are publicly available to the extent allowable under the Freedom of Information Act and FDA regulations. A list of uniform terms is provided in Appendix C. The publication may include additional information that the Agency deems appropriate to disseminate.
FDA Orange Book
The Agency will not include drug products with tentative approvals in the Orange Book because a drug product that is granted tentative approval is not an approved drug product.
When the tentative approval becomes a final approval through a subsequent action letter to the applicant, the Agency will list the drug product and the date of approval in the appropriate approved drug product list. The Agency will list the drug product in the Orange Book and the date of approval as determined under Section x. The Orange Book identifies the application holder of a drug product and does not identify distributors or repackagers.
Pharmaceutical equivalents are drug products in identical dosage forms and route s of administration that contain identical amounts of the identical active drug ingredient, i. Pharmaceutical Alternatives. Pharmaceutical alternatives are drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form, or the same salt or ester e.
Therapeutic Equivalents. Approved drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents for which bioequivalence has been demonstrated, and they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.
The concept of therapeutic equivalence applies only to drug products containing the identical active ingredient s and does not encompass a comparison of different therapeutic agents used for the same condition e.
When such differences are important in the care of a particular patient, it may be appropriate for the prescribing physician to require that a specific product be dispensed as a medical necessity. With this limitation, however, FDA believes that products classified as therapeutically equivalent can be substituted with the full expectation that the substituted product can be expected to have the same clinical effect and safety profile as the prescribed product when administered to patients under the conditions specified in the labeling.
Strength refers to the amount of drug substance contained in, delivered, or deliverable from a drug product, which includes: 1 a the total quantity of drug substance in mass or units of activity in a dosage unit or container closure e. Although the strength of drug products in the Orange Book is generally expressed in terms of the amount of drug substance active ingredient in the drug product, it is sometimes expressed in terms of the amount of the active moiety.
Bioavailability is the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by scientifically valid measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of drug action.
Bioequivalence is the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. Where these above methods are not applicable e. For example, bioequivalence may sometimes be demonstrated using an in vitro bioequivalence standard, especially when such an in vitro test has been correlated with human in vivo bioavailability data.
In other situations, bioequivalence may sometimes be demonstrated through comparative clinical trials or pharmacodynamic studies. For an ANDA based on an approved suitability petition a petitioned ANDA , the reference listed drug generally is the listed drug referenced in the approved suitability petition. Ordinarily, FDA will select the reference listed drug as the reference standard.
However, in some instances, the reference listed drug and the reference standard may be different. For example, where the reference listed drug has been withdrawn from sale and FDA has determined it was not withdrawn for reasons of safety or effectiveness, FDA may select an ANDA as the reference standard.
Listed drugs identified as reference listed drugs represent drug products upon which an applicant can rely in seeking approval of an ANDA.
In some instances when FDA has not designated a listed drug as a reference listed drug, such listed drug may be shielded from generic competition. If FDA has not designated a reference listed drug for a drug product the applicant intends to duplicate, the potential applicant may submit a controlled correspondence to the Office of Generic Drugs to ask FDA to designate a reference listed drug for that drug product.
Section 1. A potential applicant should consult Agency guidance related to referencing approved drug products in ANDA submissions for information on submitting a request for selection of a reference standard. FDA may, on its own initiative, select a new reference standard when doing so will help to ensure that applications for generic drugs may be submitted and evaluated, e.
If an applicant has a question related to the appropriate reference standard, it is recommended that an applicant planning to conduct an in vivo bioequivalence study submit a controlled correspondence to the Office of Generic Drugs.
It does not mandate the drug products that are purchased, prescribed, dispensed, or substituted for one another, nor does it, conversely, mandate the products that should be avoided. To the extent that the Orange Book sets forth FDA's evaluations of the therapeutic equivalence of drug products that have been approved, it contains FDA's advice to the public, to practitioners, and to the states regarding drug product selection.
Therapeutic equivalence evaluations are a scientific judgment based upon evidence, while generic substitution may involve social and economic policy administered by the states, e.
Rather, the exclusion may be based on the fact that FDA has not evaluated the safety, effectiveness, and quality of the drug product. Evaluations of therapeutic equivalence for prescription drugs are based on scientific and medical evaluations by FDA. Products evaluated as therapeutically equivalent can be expected, in the judgment of FDA, to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.
If products with such differences are substituted for each other, there is a potential for patient confusion, e. There may also be patient-specific allergic reactions in rare cases due to a coloring or a preservative ingredient.
FDA evaluation of therapeutic equivalence in no way relieves practitioners of their professional responsibilities in prescribing and dispensing such products with due care and with appropriate information to individual patients. In those circumstances where the characteristics of a specific product, other than its active ingredient, are important in the therapy of a particular patient, the practitioner's prescribing of that product may be appropriate.
Pharmacists must also be familiar with the different characteristics of therapeutically equivalent products, e. For such products, a therapeutic equivalence code is included and product information is highlighted in bold face and underlined. Those products with approved applications that are single-source i. The details of therapeutic equivalence codes and the policies underlying them are discussed in Section 1. Products in the Orange Book are identified by the names of the holders of approved applications applicants who may not necessarily be the manufacturer of the product.
The applicant may or may not be the manufacturer and may simply be distributing the product for which it has obtained approval. In many instances, however, the manufacturer of the product is also the applicant. The name of the manufacturer is permitted by regulation to appear on the label, even when the manufacturer is not the applicant or marketer. Although the products in the Orange Book are identified by the names of the applicants, circumstances, such as changing corporate ownership, have sometimes made identification of the applicant difficult.
U.S. Food and Drug Administration
The Agency believes, based on continuing document review and communication with firms, that the applicant designations in the Orange Book are, in most cases, correct. However, the applicant's name may not always appear on the label of the product.
If the applicant is the marketer, its name appears in the Orange Book and on the label; if the applicant is not the marketer, and the Agency is aware of a corporate relationship e. Firms with known corporate relationships are displayed in Appendix B. If there is no known corporate relationship between the applicant and the marketer, the applicant's name appears in the Orange Book; however, unless the applicant is the manufacturer, packager, or distributor, the applicant's name may not appear on the label.
In this case, the practitioner, from labeling alone, will not be able to relate the marketed product to an applicant cited in the Orange Book, and hence to a specific approved drug product. In such cases, to assure that the product in question is the subject of an approved application, the firm named on the label should be contacted.
If a corporate relationship exists between an applicant and a marketer and both firms are distributing the drug product, the FDA reserves the right to select the trade name of either the marketer or the applicant to appear in the Orange Book. If there is no known corporate relationship between the applicant and the marketer, the established drug name i. Every product in the Orange Book is subject at all times to regulatory action. In such circumstances, the Agency may commence appropriate enforcement action to correct the violation, if necessary, by securing removal of the product from the market by voluntary recall, seizure, or other enforcement actions.
Such regulatory actions are, however, independent of the inclusion of a product in the Orange Book.
Working Papers & Publications
The main criterion for inclusion of a product is that it has an application that has been approved and that has not been withdrawn for safety or efficacy reasons. FDA believes that retention of a violative product in the Orange Book will not have any significant adverse health consequences, because other legal mechanisms are available to the Agency to prevent the product's actual marketing. FDA may, however, change a product's therapeutic equivalence rating if the circumstances giving rise to the violation change or otherwise call into question the Agency's assessment of whether a product meets the criteria for therapeutic equivalence.
The coding system for therapeutic equivalence evaluations is designed to allow users to determine quickly whether the Agency has evaluated a particular approved product e. With some exceptions e. These are designated AB. Often the problem is with specific dosage forms rather than with the active ingredients.How often is the Orange Book updated? These statutorily-required notifications are intended to help the Agency understand which products are actively marketed and where there is a need for more generic competition.
U.S. Food and Drug Administration
Exclusivity Date The date the exclusivity expires. The business intelligence platform is revised daily and enables complex searches, email updates, and information in litigation, drug prices, and more. Donald Hare, a pharmacist who previously worked at the FDA is commonly referred to as 'the father of the Orange Book' and helped to select the book color. Accessed March 10,