Jeff Aronson

Centre for Evidence Based Medicine, Oxford

Naming biologics Relevance to medication errors

and adverse drug reactions

Emeritus Fellow, Green-Templeton College, Oxford

President Emeritus & Honorary Fellow British Pharmacological Society

Meyler’s Side Effects of Drugs

Side Effects of Drugs Annuals

Editor-in-Chief

What are biologics?

…such as Vaccines Blood and blood components Allergenics Somatic cells Gene therapy Tissues (e.g. corneas, skin, sperm) Recombinant therapeutic proteins

Structures Examples Sugars Heparin Proteins Monoclonal antibodies Nucleic acids Antisense oligonucleotides Complex combinations Fusion proteins Living entities (e.g. cells, tissues) Blood cells

Natural sources Humans Animals Micro-organisms

Naming medicines

MAH

WHO INN Programme

Secretariat INN Expert Panel

Rules and basic

principles

France, Japan,

Nigeria, Poland,

Russia, Singapore,

Spain, UK, USA,

Tunisia

National Nomenclature

Committees and

Regulatory Agencies

Principle 1

(guiding

principle)

International Nonproprietary Names (INN) should be distinctive in sound and spelling. They should not be

inconveniently long and should not be liable to confusion with names in common use.

Principle 2

(guiding

principle)

The INN for a substance belonging to a group of pharmacologically related substances should, where

appropriate, show this relationship. Names that are likely to convey to a patient an anatomical,

physiological, pathological or therapeutic suggestion should be avoided.

Principle 3 In devising the INN of the first substance in a new pharmacological group, consideration should be given

to the possibility of devising suitable INNs for related substances, belonging to the new group.

Principle 4 In devising INNs for acids, one-word names are preferred; their salts should be named without modifying

the acid name, e.g. "oxacillin" and "oxacillin sodium", "ibufenac" and "ibufenac sodium"

Principle 5

INNs for substances which are used as salts should in general apply to the active base or the active acid.

Names for different salts or esters of the same active substance should differ only in respect of the name

of the inactive acid or the inactive base.

Principle 6 The use of an isolated letter or number should be avoided; hyphenated construction is also undesirable.

Principle 7

To facilitate the translation and pronunciation of INN, "f" should be used instead of "ph", "t" instead of "th",

"e" instead of "ae" or "oe", and "i" instead of "y"; the use of the letters "h" and "k" should be avoided.

When devising an INN it is important to be aware of possible language problems. Since the name is used

worldwide, not only should certain letters be avoided, but experts need to be aware of unsuitable

connotations in the major languages spoken in the world.

Principle 8

Provided that the names suggested are in accordance with these principles, names proposed by the

person discovering or first developing and marketing a pharmaceutical preparation, or names already

officially in use in any country, should receive preferential consideration.

Principle 9 Group relationship in INNs (see Guiding Principle 2) should if possible be shown by using a common

stem.

Naming monoclonal antibodies

Penultimate syllable (substem A;

animal source)

Prepenultimate syllable (substem B;

general target)

Prepenultimate syllable (substem B;

tumour target)

-a- = rat -e- = hamster -i- = primate -o- = mouse -u- = human -axo- = rat-mouse hybrid -xi- = chimeric -zu- = humanized -xizu- = chimeric/ humanized hybrid -mu- = fully humanized

[-anibi- = angiogenesis inhibitor]

-b(a)- = bacterium -c(i)- = circulatory -f(u)- = fungus -gr(o) = growth factor -k(i) = interleukin [-le(s)- = inflammatory lesions] -li(m)- = immune system [-mul- = musculoskeletal] -ne- = nervous system -os- = bone -toxa- = toxin -tu(m)- = tumour (unspecified) -vi(r)- = virus

-co(l)- = colon -go(t)- = gonad (testis) -go(v)- = gonad (ovary) -ma(r)- = mammary -me(l)- = melanoma -pr(o)- = prostate

Final syllable (stem) = mab

Naming monoclonal antibodies

Tras — tu — zu — mab

Monoclonal

antibody

Humanized Tumour Whim

Naming monoclonal antibodies

Ab — ci — xi — mab

Monoclonal

antibody

Chimeric Circulatory Whim

Naming monoclonal antibodies

Ca— tum — axo — mab

Monoclonal

antibody

Rat/mouse

hybrid

Tumour Whim

Bispecific trifunctional antibody

Binding sites for two different antigens (CD3 and a tumour antigen) Binding site for Fc receptors

1. Isolated numbers, isolated characters, or hyphens

present in INNs (principle 6)

2. Prohibited graphs and digraphs present in INNs

(principle 7)

3. Word length statistics (principle 1c)

4. Use of stems to indicate pharmacological

relationships (principle 2a)

5. Patterns of similarity between INNs (principle 1d)

siplizumab anti CD2 psoriasis

ruplizumab anti CD40L lupus nephritis

teplizumab anti CD3 type 1 diabetes

Biosimilars (“follow-on biologics”)

Epoetins

Epoetin alfa Epoetin beta Epoetin theta Epoetin zeta

Epoetin lambda

Darbepoetin

Epoetins and red cell aplasia

Reports Total no. of red cell of papers aplasia Ratio Epoetin alfa 2124 90 4.24% Epoetin beta 537 45 8.38%

Heparins and thrombocytopenia

Reports Total no. of thrombo- of papers cytopenia Ratio Heparin 85032 5074 5.97% Enoxaparin 4227 236 5.58% Tinzaparin 399 31 7.77% Dalteparin 1159 93 8.02%

Conclusions

• Drug names can be difficult to read and learn

• They are supposed to be systematically formed, but there are many inconsistencies

• Similarities in names can lead to medication errors

• Biosimilars may be better prescribed by brand name in case of important differences in benefits and harms

Naming monoclonal antibodies

— le — xi — mab

Monoclonal

antibody

Chimeric Infection

Naming monoclonal antibodies

— le — xi — mab

Monoclonal

antibody

Chimeric Infection Whim

Sexi