Compendial Nomenclature

Andrzej Wilk, Ph.D. Senior Scientific Liaison Nomenclature, Safety and Labeling Expert Committee

Drug Substances/Excipients

Drug Products

Dietary Supplements

Biologics

Food Ingredients

Outline

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Drug Substances/Excipients

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Drug Substance Nomenclature Overview and

Initiatives

– United States Adopted Names (USAN)

– International Nonproprietary Names

– Japanese Accepted Names

– Drug Substance Pronunciation

Drug Substances

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Purpose:

– To serve the health professions in the U.S. by selecting

simple, informative, and unique nonproprietary names

for drugs by establishing logical nomenclature

classifications based on pharmacological and/or chemical

relationships.

United States Adopted Names (USAN) Council

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USAN

STEM DEFINITION EXAMPLES

-abine (see -arabine, -citabine)

-acetam anti-inflammatory agents (acetic acid

derivatives)

bromfenac

dexpemedolac

-adol or

-adol-

antibacterials (quinoline dioxide

derivatives)

tazadolene

spiradolene

levonantradol

-adox antiarrhythmics (propafenone

derivatives)

carbadox

-afenone PDE5 inhibitors alprafenone

diprafenonex

-afil antiarrhythmics (ajmaline derivatives) tadalafil

-aj- antacid aluminum salts lorajmine

USAN Stem Names

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STEM DEFINITION EXAMPLES

Subgroup:

-amivir neuraminidase inhibitors zanamivir

-asvir NS5A inhibitors daclatasvir

-buvir RNA polymerase (NS5B) inhibitor nesbuvir

-cavir carbocyclic nucleosides lobucavir

-cyclovir/

-ciclovir

antivirals (acyclovir type) desciclovir

famciclovir

penciclovir

-gosivir glucosidase inhibitor celgosivir

-navir HIV protease inhibitors (saquinavir

type)

droxinavir

indinavir

ritonavir

-previr serine protease inhibitors boceprevir

telaprevir

USAN Stem Names (cont.)

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USAN

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International Nonproprietary Names for Pharmaceutical Substances (INN)

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INN

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Chemical identity

Peridotaxel (Spanish)

Sukataxel (Russian)

Bakataxel (Japanese)

International considerations

Simotaxel (sim‖ oh tax’ el)

Drug Products

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The USP (or NF) titles for monograph articles are

legally recognized under the Federal Food, Drug,

and Cosmetic Act as the designations for use in

labeling the articles to which they apply.

General Chapter <1121> Nomenclature

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General Nomenclature Forms

– Some monograph titles do not conform to the formats outlined in this

chapter.

• Monograph titles adopted before the chapter establishment

• May be subject to subsequent revision and should not be

interpreted as precedents

General Chapter <1121> Nomenclature

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For a variety of dosage forms, titles are in the following

general form:

[DRUG] [ROUTE OF ADMINISTRATION] [DOSAGE FORM]

– List of specific drug products, with extensive examples can be found

in the USP Nomenclature Guidelines document (www.usp.org)

General Chapter <1121> Nomenclature

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Route of administration term omitted for dosage forms

where the route is understood

[DRUG] [DOSAGE FORM]

Examples:

– Acetaminophen and Caffeine Tablets {ORAL}

– Diazepam Capsules {ORAL}

– Benzoyl Peroxide Lotion {TOPICAL}

General Chapter <1121> Nomenclature

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Available online at:

– http://www.usp.org/usp-nf/development-process/compendial-nomenclature

Example:

Nomenclature Guidelines

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Ointments

Ointments are semisolid preparations usually containing less than 20%

water and volatiles, and more than 50% hydrocarbons, waxes, or

polyols as the vehicle. Ointments are generally intended to be applied

topically to the skin or to a mucous membrane. Any other administration

route shall typically be reflected in the compendial name. However,

rectally administered ointments can often be applied topically as well,

and would not include the rectal route in the name even if labeling is

targeted for rectal use.

Examples:

Nomenclature Guidelines

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Ointments Nomenclature

[DRUG] [ROUTE OF ADMINISTRATION] Ointment

[DRUG] Ointment (Bacitracin Ointment, Fluocinolone Acetonide Ointment)

[DRUG] Nasal Ointment (Mupirocin Nasal Ointment)

[DRUG] Ophthalmic Ointment (Neomycin and Polymyxin B Sulfates and

Bacitracin Ophthalmic Ointment, Vidarabine Ophthalmic Ointment)

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Monograph Naming Policy

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Monograph Naming Policy

Molecular Weight: 194.19

Molecular Weight: 386.31

Monograph Naming Policy

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MONOGRAPH NAMING POLICY FOR SALT DRUG SUBSTANCES IN

DRUG PRODUCTS AND COMPOUNDED PREPARATIONS

The titles of USP monographs for drug products and compounded

preparations with a salt of an acid or base use the name of the active

moiety

Strength expressed in terms of the active moiety.

– For example, the active moiety of a hydrochloride salt of a base will be the free base

and not the protonated form of the base. The active moiety of a metal salt of an acid

will be the free acid.

This Policy is followed for drug products and compounded preparations

newly recognized in the USP.

Revising existing monographs to conform to this Policy is not intended,

except for reasons such as safety, a nomenclature change is warranted.

MONOGRAPH NAMING POLICY FOR SALT DRUG SUBSTANCES IN

DRUG PRODUCTS AND COMPOUNDED PREPARATIONS (cont.)

Labeling

– Clearly states the specific salt form of the active moiety that is present in the

product/preparation

– Names and strengths of both the active moiety and specific salt form are provided

Exceptions

– May be considered in those rare cases in which the use of the specific salt form of the

active moiety in the title provides vital information from a clinical perspective

– In such cases, the monograph title contains the specific salt form of the active moiety,

the strength of the product or preparation also is expressed in terms of the specific salt

form.

Monograph Naming Policy

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21 CFR

314.108 New drug product exclusivity

(a) Definitions

– The following definitions of terms apply to this section:

– Active moiety means the molecule or ion, excluding those appended

portions of the molecule that cause the drug to be an ester, salt

(including a salt with hydrogen or coordination bonds), or other

noncovalent derivative (such as a complex, chelate, or

clathrate) of the molecule, responsible for the physiological or

pharmacological action of the drug substance.

Active Moiety

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Monograph Naming Policy

Dietary Supplements

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Dietary Supplements

Dosage forms

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Dietary Supplements

Identification of the source

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Dietary Supplements

Identification of the source

Biologics

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Biologics

Epoetin USAN INN BAN JAN

Alpha

Beta

Delta

Epsilon

Gamma

Kappa

Omega

Theta

Zeta

Well characterized biologics – examples

Protein and peptide hormones

Biologics

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Biologics

Grandfathered biologics - examples

Antivenins

Guidance for Industry on Biosimilars:

Q & As Regarding Implementation of the BPCI Act of 2009

Questions and Answers Part II

…….

A.II.1. (Proposed Answer): The BPCI Act amends the definition of “biological product” in

section 351(i) of the PHS Act to include a “protein (except any chemically synthesized

polypeptide)” and provides that an application for a biological product must be

submitted under section 351 of the PHS Act, subject to certain exceptions during the

10-year transition period ending on March 23, 2020, described in section 7002(e) of

the Affordable Care Act.

FDA has developed the following regulatory definitions of “protein” and “chemically

synthesized polypeptide” to implement the amended definition of “biological product”

and provide clarity to prospective applicants regarding the statutory authority under

which products will be regulated.

Protein — The term “protein” means any alpha amino acid polymer with a specific

defined sequence that is greater than 40 amino acids in size.

Compounds greater than 40 amino acids in size will be scrutinized to determine whether

they are related to a natural peptide of shorter length and, if so, whether the additional

amino acids raise any concerns about the risk/benefit profile of the product.

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BIOSIMILARS in the US (FDA)

Chemically synthesized polypeptide — The term ―chemically synthesized

polypeptide‖ means any alpha amino acid polymer that (1) is made entirely by

chemical synthesis; and (2) is less than 100 amino acids in size.

A chemically synthesized polypeptide, as defined, is not a ―biological product‖

and will be regulated as a drug under the FD&C Act unless the polypeptide

otherwise meets the statutory definition of a ―biological product.‖

Chemically synthesized compounds greater than 99 amino acids in size will be

scrutinized to determine whether they are related to a natural peptide of shorter

length and, if so, whether the additional amino acids raise any concerns about

the risk/benefit profile of the product.

Biosimilars in the US (cont.)

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Biosimilars in Europe (source EMA)

Name Active substance Therapeutic area Status

Abseamed epoetin alfa Anemia Cancer Kidney Failure, Chronic Authorised

Alpheon recombinant human interferon alfa-2a Hepatitis C, Chronic Refused

Binocrit epoetin alfa Anemia Kidney Failure, Chronic Authorised

Biograstim filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Authorised

Epoetin Alfa Hexal epoetin alfa Anemia Cancer Kidney Failure, Chronic Authorised

Filgrastim Hexal filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Authorised

Filgrastim ratiopharm filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Withdrawn

Nivestim filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Authorised

Omnitrope somatropin Dwarfism, Pituitary Prader-Willi Syndrome Turner Syndrome Authorised

Ratiograstim filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Authorised

Retacrit epoetin zeta Anemia Blood Transfusion, Autologous Cancer Kidney Failure, Chronic Authorised

Silapo epoetin zeta Anemia Blood Transfusion, Autologous Cancer Kidney Failure, Chronic Authorised

Tevagrastim filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Authorised

Valtropin somatropin Dwarfism, Pituitary Turner Syndrome Withdrawn

Zarzio filgrastim Cancer Hematopoietic Stem Cell Transplantation Neutropenia Authorised

Food Ingredients

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PURE FINEST FOOD

GRADE COCONUT OIL

– Virgin

– Cold-pressed

– Unrefined

– Unbleached

– Unhydrogenated

– Undeodorized

Food and Food Ingredients

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USP Dictionary of USAN

and International Drug Names

Andrzej Wilk, Ph. D. Senior Scientific Liaison Nomenclature, Safety and Labeling Expert Committee

Sources of Drug Substance Names

o United States Adopted Names (USAN)

o International Nonproprietary Names (INN)

o USP-NF

o Japanese Accepted Names (JAN)

o British Approved Names (BAN)

o French Approved Nonproprietary Names (DCF)

o Merck Index (MI)

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USP Dictionary

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USAN

The purpose of the United

States Adopted Names (USAN)

Council is to serve the health

professions in the United

States by selecting simple,

informative, and unique

nonproprietary names for drugs

by establishing logical

nomenclature classifications

based on pharmacological

and/or chemical relationships.

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USAN

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INN

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INN

USAN process (source – USANC/AMA)

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http://www.ama-assn.org/ama/pub/physician-resources/

medical-science/united-states-adopted-names-council.page?

USP Dictionary

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Highlights & Features

The 2013 edition, available April 1, 2013, features the latest drug name

updates and information, including:

11,304 nonproprietary drug name entries—more than 1,400 are new or

revised!

5,152 United States Adopted Names

3,470 brand names

9,501 graphics—more than 600 are new

571 new code designations

586 new CAS registry numbers

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