{
  "id": "R46110",
  "type": "CRS Report",
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  "number": "R46110",
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      "title": "Defining Active Ingredient: The U.S. Food and Drug Administration\u2019s Legal Interpretation of Regulatory Exclusivities",
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      "source": "CRSReports.Congress.gov",
      "typeId": "R",
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      "source": "EveryCRSReport.com",
      "id": 610605,
      "date": "2019-12-10",
      "retrieved": "2019-12-13T14:59:14.348938",
      "title": "Defining Active Ingredient: The U.S. Food and Drug Administration\u2019s Legal Interpretation of Regulatory Exclusivities",
      "summary": "Whether many provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) apply to a particular drug product turns in part on the novelty of the \u201cactive ingredient\u201d of the drug in question. In particular, the Food and Drug Administration (FDA) must assess the novelty of the active ingredient in a new drug, comparing it to a previously approved drug\u2019s active ingredient to determine whether the new drug qualifies for the five-year \u201cnew chemical entity\u201d (NCE) exclusivity. FDA generally cannot accept new drug applications that refer to a drug with NCE exclusivity (i.e., rely on its clinical data and FDA\u2019s approval of the drug) for five years. Companies that receive approval for drugs with new active ingredients generally enjoy a competitive advantage in the market while the exclusivity is in effect\u2014and after, depending how long it takes for generic versions to receive approval once applications can be submitted. \nComparing active ingredients can be technically quite complicated. For instance, compounds in a final drug product may convert to other compounds through chemical reactions inside the body before arriving at the site of the therapeutic effect. In addition, related but distinct drug molecules may be clinically indistinguishable or convert into the same pharmacologically or physiologically active component inside the body. Alternatively, two drug molecules with the same core compound may have different compounds appended to them by either covalent or noncovalent bonds. For example, replacing a hydrogen atom in an acid molecule with \u201ca metal or its equivalent\u201d forms a salt, while replacing the hydrogen atom with \u201can organic radical\u201d forms an ester. These derivatives may or may not vary from each other in clinically significant ways. This raises the question of which derivative(s), if any, should be considered to be the same active ingredient as the core or base molecule. Generally, a more expansive interpretation of phrase \u201cactive ingredient,\u201d that is, one that considers more types of derivatives to be the same active ingredient, reduces the number of drugs eligible for NCE regulatory exclusivity by expanding the drug ingredients considered previously approved, which allows for earlier introduction of generic versions of those drugs. \nHistorically, for the exclusivity provisions, FDA has interpreted \u201cactive ingredient\u201d to mean \u201cactive moiety,\u201d as defined by FDA regulations. FDA generally defines active moiety as the core molecule or ion of a drug (i.e., the drug molecule without certain appendages) that is \u201cresponsible for the physiological or pharmacological action of a drug substance.\u201d FDA\u2019s interpretation has generated disputes between FDA and pharmaceutical companies, as FDA\u2019s approach tends to exclude some drugs from being afforded five-year NCE exclusivity under the FD&C Act. In 2015, a federal district court rejected FDA\u2019s interpretation as inconsistent with the statutory language, though it did not explicitly invalidate FDA\u2019s regulations. \nIn the 116th Congress, legislation has been introduced that would generally codify FDA\u2019s current approach to evaluating NCE exclusivity and extend that approach to certain other provisions under the FD&C Act. This proposed legislation would moot questions about the validity of FDA\u2019s interpretation and clarify when chemical entities are sufficiently similar to be considered identical for purposes of drug approval and exclusivity.",
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      "topics": [
        {
          "source": "IBCList",
          "id": 4880,
          "name": "FDA Product Regulation & Medical Research"
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}