Preface to FDA orange peel book

Preface of the 38th edition of FDA orange peel book Under the guidance of the federal food, drug, and Cosmetic Act (ACT), this publication, drugs approved by the evaluation of therapeutic equivalence (the well-known Orange Book), is recognized by the Federal Food and Drug Administration (FDA) on the basis of safety and effectiveness The main criterion for a drug to contain a substance is that the application for approval of the drug is valid and has never been withdrawn for safety or effectiveness Through administrative and judicial restrictions on drugs, the listed drug ingredients are not subject to any current regulations In addition, the catalogue contains an evaluation of the therapeutic equivalence of approved multi-source prescription drugs These evaluations will be used to provide public information and suggestions to state health institutions, prescription doctors and pharmacists to promote public awareness in the field of drug selection and develop awareness of health care cost control The evaluation of therapeutic equivalence in this publication is not an official FDA action that affects the legal status of a drug under the guidance of the act Background of this publication In fact, every state has laws or regulations to encourage drug substitutes to control the cost of drugs State laws require these substitutes to be either restricted (active prescription Pharmacopoeia) in a specific catalog or applicable to all drugs except those prohibited in a specific catalog (passive prescription Pharmacopoeia) Based on the number of active and passive prescription Pharmacopoeia requests for FDA assistance in the late 1970s, it is clear that FDA cannot serve each state on a single basis The authorities also believe that the provision of a single catalogue based on general principles would be beneficial for the evaluation of drugs based on different definitions and legal standards of different states Therefore, on May 31, 1978, the U.S FDA Regulatory Commission sent a letter to the chief executive of each state, stating that FDA is willing to provide a list of all prescription drugs approved by FDA based on safety and effectiveness, as well as the evaluation of the therapeutic equivalence of multi-source prescription drugs In January 1979, the orange peel book was distributed to the States as a proposal It only includes prescription drugs approved by FDA through new drug application (NDA) and simplified new drug application (anda) under the guidance of article 505 of the act The evaluation of therapeutic equivalence in the orange peel book reflects the specific standards of multi-source prescription drugs approved based on article 505 of the act These evaluations are represented in code letters that represent the basis of the evaluation For more information on these codes, see the "preface." A full discussion of the background and basis of the U.S FDA treatment equivalence evaluation policy was published in the Federal Register on January 12, 1979 (44 fr 2932) The final rule, which includes FDA feedback to the public, was also published in the Federal Register on October 31, 1980 (45 fr 72582) The first edition of the final edition of the orange peel book (October 1980) contains appropriate amendments and supplements Each subsequent edition contains new approvals and appropriate modifications to the data On September 24, 1984, the president signed the drug price competition and patent Recovery Act (hatch Waxman Amendment) The hatch Waxman amendment requires the FDA to issue a list of approved drugs to the public in a monthly supplement Orange Book monthly accumulation supplement to meet this demand This appendix identifies the exclusive right period of drugs under the guidance of the food, drug and Cosmetics Act and provides the patent information of the included drugs The appendix also provides additional information to assist companies that submit new drug applications to the FDA 1 Preamble 1.1 including and excluding contents Orange peel book is composed of four parts: (1) approved prescription drugs with therapeutic equivalence evaluation; (2) approved over-the-counter drugs (OTC), which are not included in the existing OTC monograph, so they cannot be marketed without new drug application or simplified new drug application; (3) under the guidance of article 505 of the act, approval supervised by biological evaluation and Research Center Drugs; (4) a cumulative list of approved drugs that have never been marketed, or used for export or military purposes, or have been discontinued on the market, or have been discontinued on the market due to withdrawal of an application for reasons other than safety or effectiveness This publication also contains a catalog of prescription and over-the-counter drugs in the order of trade name or established name (if the trade name does not exist) and applicant organization name (the owner of the approved application) All identified names of the active ingredients are consistent with the official Pharmacopoeia name or usan (21 CFR 299.4 (E)) The latter contains the abbreviated name of the applicant in this publication In addition, Appendix C provides a list of uniform terms The appendix contains the list of prescription drugs, over-the-counter drugs, out of use drugs, and the patent and exclusive information of drugs supervised by the biological evaluation and Research Center under the guidance of article 505 of the act This publication also contains additional information that FDA considers appropriate for publication Prior to the sixth edition, this publication did not include over-the-counter drugs and drugs approved by the center for biological evaluation and research based on section 505 of the act, because the main purpose of this publication is to provide states with information recommended by FDA, that is, when selecting drugs, generic prescription drugs are also optional items The hatch Waxman amendment requires the FDA to publish in real time the latest catalog of all marketed drugs (over-the-counter and prescription drugs), which are approved for their safety and effectiveness as well as their required new drug applications Under the guidance of the food, drug and Cosmetics Act, some drugs have been approved temporarily FDA will not include the temporarily approved drug in the orange peel book because the temporary approval is not an approved product The catalogue of temporary approval is recorded in the simplified new drug application (generic drugs), which can be viewed in the FDA drug database When an interim approval becomes a full approval through a subsequent action letter to the applicant, FDA will list the drug and the final approval period in the appropriate approved drug catalog The dealer or repacker in the orange book is uncertain 1.2 pharmaceutical equivalence is a term related to therapeutic equivalence If a drug product contains the same active ingredient, dosage form and route of administration, and the formula contains the same amount of active ingredient and meets the same pharmacopoeia or other standards (for example, dosage, quality, purity, identification, etc.), they are considered pharmaceutical equivalent They may vary in shape, scoring, release mechanism, packaging, excipients (including colorants, fragrances, preservatives), expiry date, labeling, etc Drug substitutes If the drug contains the same therapeutic ligand but different salts, ester groups or complex components, or different dosage forms or doses (such as 250mg tetracycline hydrochloride capsules vs 250mg compound tetracycline phosphonate capsules; 200mg quinidine sulfate tablets vs 200mg quinidine sulfate capsules), such drugs are considered as drug substitutes Drugs of different dosage forms and specifications of the same manufacturer in a product line are drug substitutes, for example, when slow-release drugs are compared with quick release or standard release preparations of the same active ingredient Treatment equivalence Only when the bioequivalence of the drug has been proved to be pharmaceutical equivalent, and the drug is expected to have the same clinical effect and safety when it is used in the manual to adapt to the population, it is regarded as treatment equivalent FDA determines that drugs meeting the following general standards have therapeutic equivalence: (1) approved for safety and effectiveness; (2) pharmaceutical equivalence is satisfied for the following aspects: (a) the same dosage form and route of administration, and the same active ingredients with the same dosage; (b) pharmacopoeia or other applicable standards that meet the specifications, quality, purity and drug resistance; (3) bioequivalence is due to (a) There is no known or potential bioequivalence problem, and it meets the acceptable in vitro standard (b) if there is known or potential problem, but it meets the appropriate bioequivalence standard; (4) the mark is accurate; (5) it is produced according to the current good manufacturing practice The concept of therapeutic equivalence has been used to develop the orange peel book, which is only applicable to drugs with the same active ingredients and does not include the comparison of different therapeutic products under the same conditions (for example, pethidine hydrochloride vs morphine sulfate for analgesia) Any product in the orange peel book, when repackaged or distributed by someone other than the applicant, is considered equivalent to the drug treatment of the applicant, even if the applicant's drug is a single source or coded as non equivalent (such as BN) Distributors and sub packers shall not list the products distributed or sub packed by the applicant in the orange peel book FDA believes that drugs that meet the above criteria have therapeutic equivalence, even if the drugs differ in some characteristics, such as shape, indentation consistency, mechanism of action, packaging, excipients (including color, taste, preservative), expiration date, some aspects of the instructions (such as specific pharmacokinetic information) and storage conditions When these differences are important for a particular patient, the prescribing physician can obtain this information and prescribe other products necessary for the patient However, FDA believes that drugs defined as therapeutic equivalence are likely to be replaced, because the substitute drugs have the same clinical effect and safety as the reference drugs Dosage Dose refers to the content of drugs that have been or can be transferred in the drug, which includes: (1) (a) the quantity of drugs contained in the drug unit or the total or unit in the package (for example, the weight / dose, weight / volume, weight / weight, or the unit / volume in the package, unit / weight) (b) the concentration of drugs in the total or unit drug (for example, weight / volume, Weight / weight, unit / volume) (2) Other decisions created by FDA that determine the amount of drugs that have been or can be delivered in a drug do not apply to the concept of "dose" if: (1) (a) certain drugs or drugs that are discharged per time or unit time from a drug device combination product It should be noted that the FDA will not modify the description of drug dosage in the orange peel book, but will use prospective standards for products entering the orange peel book, if the decision created by the FDA or the standard describing drug content in the drug changes over time Although the dosage in the orange peel book is generally expressed in terms of drugs (active ingredients), sometimes it is also expressed in terms of active parts For example, some drugs in the orange peel book are designated "EQ" in the column after the dose description "EQ" is used for a salt containing drug to indicate the content of the active part of the drug rather than the content of the active component Bioavailability The term refers to the ratio and degree to which (the body) absorbs active ingredients or active ligands from a drug product and produces potency For drugs that are not absorbed by the blood, bioavailability can be determined by the experiment that the active components or active ligands are reflected in the active sites Bioequivalence Bioequivalence refers to the use of molar doses of reference drugs and alternative drugs such as active ingredients or active sites in the drug action site under fully designed similar test conditions There is no significant difference in speed or degree between the two drugs Section 505 (J) (8) (b) of the act explains the conditions under which experimental and reference drugs (see Chapter 1.4) are considered bioequivalent: