Clinical Pharmacology Important Terms

Abbreviated New Drug Application (ANDA)

Orange Book Therapeutic Equivalence (TE) Codes

DEA Schedules of Controlled Substances

Patent and Exclusivity Information

FDA Pregnancy Risk Categories

Pharmaceutical Equivalents

Medication Guides (MedGuides)

Reference Listed Drugs

National Drug Codes (NDC)

REMS (Risk Evaluation and Mitigation Strategies)

New Drug Application (NDA)

Supplemental New Drug Application

 

Therapeutic Equivalence (TE)

 

Abbreviated New Drug Application (ANDA)

An Abbreviated New Drug Application (ANDA) contains data that, when submitted to FDA's Center for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product. Generic drug applications are called "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. Instead, a generic applicant must scientifically demonstrate that its product is bioequivalent (i.e., performs in the same manner as the innovator drug or Reference Listed Drug, RLD). For internal tracking purposes, all ANDA's are assigned an ANDA number.

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DEA Schedules of Controlled Substances

Federal Schedules of Controlled Substances are outlined as follows:

(http://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm)

Schedule I

(A) The drug or other substance has a high potential for abuse.

(B) The drug or other substance has no currently accepted medical use in treatment in the United States.  

(C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Schedule II

(A) The drug or other substance has a high potential for abuse.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions.

(C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

Schedule III

(A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

Schedule IV

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

Schedule V

(A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV.

(B) The drug or other substance has a currently accepted medical use in treatment in the United States.

(C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.

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FDA Pregnancy Risk Categories

A

Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.

B

Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women.

or

Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus.

C

Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women.

or

No animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.

D

Studies, adequate well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk.

X

Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant.

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Medication Guides (MedGuides)

Medication Guides (MedGuides) are paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. Medication Guides are separate and distinct from other sources of consumer medication information (CMI), including Patient Package Inserts.

The FDA requires that Medication Guides be issued with certain prescribed drugs and biological products when the Agency determines that:

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National Drug Codes (NDC)

Each drug product regulated under Section 510 of the Federal Food, Drug, and Cosmetic (FDA) Act is assigned a unique 10-digit, 3-segment number. This number, known as the National Drug Code (NDC), identifies the labeler/vendor, product, and trade package size.

NOTE: Both the product and package codes are assigned by the firm.

On the product labeling, the NDC is provided in one of the following configurations: 4-4-2, 5-3-2, or 5-4-1.

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New Drug Application (NDA)

When the sponsor of a new drug believes that enough evidence on the drug's safety and effectiveness has been obtained to meet FDA's requirements for marketing approval, the sponsor submits to FDA a new drug application (NDA). The application must contain data from specific technical viewpoints for review, including chemistry, pharmacology, medical, biopharmaceutics, and statistics. If the NDA is approved, the product may be marketed in the United States. For internal tracking purposes, all NDA's are assigned a NDA number.

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Orange Book Therapeutic Equivalence (TE) Codes

(http://www.fda.gov/cder/ob/default.htm)

The coding system for therapeutic equivalence evaluations allows users to determine whether FDA has evaluated a particular approved product as therapeutically equivalent to other pharmaceutically equivalent products (first letter) and to provide additional information on the basis of FDA's evaluations (second letter). Sample TE codes: AA, AB, BC.

Some drug products have more than one TE Code. Over-the-counter drugs are not assigned TE codes.

Clinical Pharmacology will indicate where a TE code does not apply.

"NR" (Not Rated) - Products listed in the Orange Book that are not multi-source (i.e., no FDA-approved generic equivalents).  

"NA" (Not Applicable)- Products that are not reviewed by the FDA such as those marketed before 1938, vitamins, and nutritional supplements.

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Patent and Exclusivity Information

(Also see Orange Book Frequently Asked Questions section: http://www.fda.gov/cder/ob/faqs.htm)

Patents are granted by the patent and trademark office anywhere along the development lifeline of a drug and can encompass a wide range of claims. However, Exclusivity is granted by the FDA upon approval of a drug and pertains to exclusive marketing rights for a drug product. Exclusivities may or may not run concurrently with a patent. Exclusivity is a statutory provision and is granted to an NDA applicant if statutory requirements are met (see 21 C.F.R. 314.108) and were designed to promote balance between new drug development and generic competition.

Common exclusivities granted by the FDA include:

Orphan Drug (ODE) - 7 years

New Chemical (NCE) - 5 years

"Other" Exclusivity - 3 years for a "change" if criteria are met

Pediatric Exclusivity (PED) - 6 months added to existing Patents/Exclusivity

Patent Challenge (PC) – 180 days (this exclusivity is for ANDAs only)

Pediatric exclusivity is unique in how this exclusivity is applied. When pediatric exclusivity is granted to a drug product, a period of 6 months exclusivity is added to all existing patents and exclusivity on all applications held by the sponsor for that active moiety.  The term "PED" is added in the exclusivity column and is linked to exclusivity formerly granted. In the patent column, the patent is shown twice; once with the original patent expiration date and a second time with the "PED" added to reflect additional the six month period of EXCLUSIVITY that links to that particular patent.

To view current patent terms see:

http://www.accessdata.fda.gov/scripts/cder/ob/docs/pattermsall.cfm

To view current exclusivity terms, see:

http://www.accessdata.fda.gov/scripts/cder/ob/docs/excltermsall.cfm

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Pharmaceutical Equivalents

FDA considers drug products to be pharmaceutical equivalents if they meet the following three criteria:

Pharmaceutically equivalent drug products may differ in characteristics, such as:

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Reference Listed Drugs

A Reference Listed Drug (RLD) is an approved drug product to which new generic versions are compared to show that they are bioequivalent. A drug company seeking approval to market a generic equivalent must refer to the Reference Listed Drug in its Abbreviated New Drug Application (ANDA). By designating a single reference listed drug as the standard to which all generic versions must be shown to be bioequivalent, FDA hopes to avoid possible significant variations among generic drugs and their brand name counterpart.

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REMS (Risk Evaluation and Mitigation Strategies)

The Food and Drug Administration (FDA) has the authority to require a Risk Evaluation and Mitigation Strategy (REMS) from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks. The components of a REMS may include one or more of the following:

To view a list of FDA-approved REMS, see:

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm

 

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Supplemental New Drug Application

Companies are allowed to make changes in a product their labels that already have an approved new drug application (NDA). To change a label, market a new dosage or strength of a drug, or change the way it manufactures a drug, a company must submit a supplemental new drug application (sNDA). CDER must approve all important NDA changes (in packaging or ingredients, for instance) to ensure the conditions originally set for the product are still met.

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Therapeutic Equivalence (TE)

Drug products classified as therapeutically equivalent can be substituted with the full expectation that the substituted product will produce the same clinical effect and safety profile as the prescribed product. Drug products are considered to be therapeutically equivalent only if they meet these criteria:

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