[exclusive] interpretation of us new drug application classification code (translation)

Objective this paper introduces the NDA classification code based on product characteristics signed by CDER This code was previously considered as a chemical classification code Background NDA classification code provides a method to summarize new drug applications The code derives from the management and specification of drug application based on product characteristics Application classification based on product characteristics helps to manage the working load of CDER, promote the continuity of evaluation, and make it possible to review and analyze the trend, staff plan and policy development NDA classification codes are not determined by exclusivity The code does not indicate the novelty or therapeutic value of a specific product 3 Policy FDA shall specify the NDA classification code and reevaluate it when approving the application through the application date The evaluation is based on products that have been approved or marketed in the United States at that time After the application is approved, FDA will still reevaluate the classification code FDA can temporarily determine the classification code for the clinical application (ind) before the product is put on the market This approach is useful for considering whether a product in a clinical trial contains a new substance entity (NME) At the clinical stage, any decision on the chemical type will become part of the review, and can be revised after the application, approval and approval of listing When the same applicant submits and approves two or more NME type NDA applications for the same active ingredient at the same time, only one NDA application is retained In this case, the NDA determines the classification based on the factors rather than the time of submission For example, a fully detailed NDA application will be given code type 1, and other NDA will be given code type 3 or type 5 4 NDA classification code tpye 1 new molecular entity (NME) type 1 NDA application is suitable for drugs containing new molecular entity NME is an active ingredient that does not contain active entities of drugs that have been filed under the food, drug, and cosmetic act or have been marketed in the United States Pure optical isomers or racemic mixtures are NME only when neither has been approved or marketed An NDA application should be considered as type 7 rather than type 1 if it contains an active ingredient that is listed but not approved In the NDA application of compound products, if the active ingredient contains an NME and other approved active parts, FDA will classify it as a new compound drug containing NME with the classification code of type 1,4 Radioactive drugs not approved by FDA or listed in the United States are NME In addition, if the active part caused by changing element isotopes (for example, 131I becomes 123I, 12C becomes 13C) is not approved by FDA or not listed in the United States, its active component is NME Type 2 new active ingredient type 2 NDA application product contains new active ingredient, but not NME The new active ingredient contains the approved or listed active entity in the United States, and is a specific ester, salt or noncovalent bond derivative of the active entity without approval or listing Similarly, if its ester, salt or noncovalent bond derivative has been listed, the unmodified molecular entity can only be used as a new active component, rather than NME The indications of the drug do not need to be the same as the same active entity already on the market If the active ingredient is an enantiomer and the racemic mixture contains an FDA approved or US listed enantiomer, or the active ingredient is a racemic mixture and contains an FDA approved or US listed enantiomer, the NDA application will be classified as type 2 Type 3 new dosage form NDA application of type 3 is applicable to a new dosage form whose active ingredient is not approved or is not listed in the United States The indications applied for such products do not need to be the same as the products already on the market Once a new dosage form of an active ingredient is approved, subsequent applications for the same dosage form of the same active ingredient should be classified as type 5 New combination of type 4 NDA application of type 4 is applicable to two or more new compounds with active ingredients If there is a new molecular entity or active ingredient, there may be more than one NDA application category for the new compound The new product can be a physical combination of two or more active parts or a chemical mixture A physical combination of two or more active ingredients may be combined in a single agent or packaged together using a combined label If there is a new molecular entity, the NDA application of the compound is classified as type 1,4 If there are new active ingredients, the NDA application of the compound preparation is classified as type 2,4 If the NDA application for an active ingredient is two or more approved or listed active parts connected by ester bond through chemical combination, and the application for physical combination of the above-mentioned active parts has not been approved before, in this case, the application is classified as type 2,4 If the NDA application of physical association has been approved, the application will not be regarded as a new compound, and its NDA application classification will be classified as type 2 Type 5 new format or other different (new indication, new applicant, new manufacturer) type 5 NDA application is for products rather than for new dosage forms, which is different from products that have been approved or have been launched in the United States due to the following reasons: 1 For the change of auxiliary materials of products, bioequivalence study or clinical study is required for approval and the original application for NDA is submitted instead of the supplementary application for approved products 2 The product is a generic drug (the same API, the same dosage form, the same or different indications, the same compound) applied by another applicant, and (a) requires bioequivalence (be) test, but is not qualified to submit the application as the applicant; or (b) requires safety and effectiveness test due to the use of new excipients; or (c) All safety and effectiveness tests are required for the following reasons: (I) encountering other applicants' exclusive rights, or (II) biotechnology products whose safety and effectiveness cannot be achieved through be test, or (III) unprocessed natural products, or (IV) not eligible for application due to different bioavailability (BA) (for example, different drug release characteristics of the product), or 3 The active ingredient or active entity of the product is included in the corresponding active ingredient or entity of the approved or marketed compound preparation in the United States This applies when the active ingredient has been approved or marketed as part of a compound preparation, or as part of a recombinant DNA technology or a mixture from a natural source 4 The compound product contains at least one active ingredient less than the listed compound preparation or replaces the original active ingredient with ester, salt and non covalent bond The latter's NDA application should be classified as type 2,5 5 The active ingredients in the compound product are the same as those of the approved or marketed compound preparation, but the dosage is different Type 5 NDA applications are generally submitted by new applicants rather than holders of approved products Similar applications submitted by holders of approved products shall be submitted as supplementary applications 6 Due to different bioavailability (BA), the product does not meet the Anda application 7 Products that use new plastic packaging containers and need to do safety research outside the confirmation test For new indication application or declaration submitted by the same applicant of type 6, the classification code of such NDA application is no longer used, instead of type 9 and type 10 This category code is reserved for historical reasons The NDA application classification code of type 6 is used before July 27, 2009 It is applicable to the applicant to copy the approved or listed products in the United States held by him / her, only when the indication and declaration are different from the imitated products Type 7 listed but unapproved NDA application type 7 NDA application classification is applicable to products that are listed but contain active parts that have not been applied for or approved These classification codes are only applicable to products containing the following active ingredients The NDA application of type 7 includes but is not limited to the following situations: (1) the first application after 1962 for the active part which was listed before 1938; (2) the first application for the active part which was listed between 1938 and 1962 for the first time is the same, related or similar (IRS) product of the drug efficacy research implementation notice (DESI) (3) First applied IRS product launched after 1962 (4) After 1962, it was the first application for the products without NDA application for the listed active ingredients The NDA application of type 8 prescription drug transferred to OTC type 8 is applicable to the previously approved or marketed drugs containing active ingredients circulated by prescription, and now it is intended to change to OTC drugs (OTC switch) The NDA application of type 8 provides different dosage forms, doses, administration forms or indications compared with the previously approved prescription drugs If OTC switch wants to transfer all indications, usage and dosage of prescription drugs to over-the-counter, the original holder needs to submit a supplementary application If a new applicant wants to transfer only part of the indications, usage and dosage to over-the-counter, the new NDA application to be submitted is classified as type 8 Application for new indications or declaration of products that type 9 does not intend to market In general, type 9 NDA applications are submitted as a separate NDA application When an NDA application of type 9 is submitted, it will get the same classification as the NDA application to be evaluated When one of them is approved, the other, whether the first or the second application, will also be classified as type 9 After the type 9 NDA application is approved, FDA will administratively close it and then only accept its "parent NDA" Type 10 will be applied to pending or approved products according to new indications of type 10 NDA or declared product type 10 NDA application after being launched, and the applicant intends to apply for products listed as independent type 10 NDA after approval Type 10 NDA applications are generally suitable for products with new indications or claims, and the labels and proprietary names of these products will be different from the original NDA Note: when the type 10 NDA application is submitted, it will obtain the same NDA classification code as the original NDA application, unless the original NDA application has been approved When one of the NDA applications is approved, regardless of the time of submission, the other NDA application will be classified as type 10 Appendix (definition of some terms) act: the federal food, drug, and Cosmetic Act Active ingredient: pharmaceutical ingredients that provide pharmacological activity or other ingredients that play a direct role in the diagnosis, cure, treatment, alleviation and prevention of diseases, or can affect the structure and function of human or animal body The component may be a separate chemical or its noncovalent bond derivative or ester The ingredient can also be a mixture obtained from nature Active moiety: a pharmaceutical substance that produces physiological or pharmacological activity after the elimination of the ester group, salt or other noncovalent derivatives added to the exciton or ion New chemical entity (NCE): as defined in 21 CFR 314.108 (a), an nce is a drug that contains an active part that is not contained in a drug approved by the FDA under section 505 (b) of the act New molecular entity (NME): an NME is an active ingredient that contains an active part of a drug approved by the FDA under section 505 (b) of the act or that has been marketed in the United States NDA classification code: FDA evaluates the current submission