Saatja: <
[email protected]>
Saadetud: 28.02.2023 17:08
Teema: WHO: C.L.5.2023 (Substitution of recommended INN)
Manused: C.L.5.23 Substitution of recommended INN (Arabic).pdf; C.L.5.23 Substitution of
recommended INN (Chinese).pdf; C.L.5.23 Substitution of recommended INN (English).pdf;
C.L.5.23 Substitution of recommended INN (French).pdf; C.L.5.23 Substitution of
recommended INN (Russian).pdf; C.L.5.23 Substitution of recommended INN (Spanish).pdf
Dear Member States of the World Health Organization,
Please find attached, in the six official languages, C.L.5.2023 regarding the substitution of a
recommended international nonproprietary name.
Best regards,
Department of Governing Bodies
World Health Organization
***DO NOT RESPOND TO THIS E-MAIL. YOU WILL NOT RECEIVE A REPLY***
20, AVENUE APPIA – CH-1211 GENEVA 27 – SWITZERLAND – TEL CENTRAL +41 22 791 2111 – FAX CENTRAL +41 22 791 3111 – WWW.WHO.INT
Ref.: C.L.5.2023
The World Health Organization (WHO) presents its compliments and would be grateful if
this communication could be forwarded to the drug regulatory authority or other appropriate
office dealing with the use on international nonproprietary names (INN) for pharmaceutical
substances.
The World Health Organization has received a proposal to substitute the recommended
INN “upifitamab” (122)(84) and “upifitamab rilsodotin” (123)(85) to upinitatug and upinitatug
rilsodotin and has referred this proposal to the members of the WHO Expert Advisory Panel on
the International Pharmacopoeia and Pharmaceutical Preparations, designated for the purpose of
selecting recommended INN (“the INN Expert Group”). “upifitamab” was published in 2020 in
List 84 of recommended INN,1 and “upifitamab rilsodotin” was published in 2021 in List 85 of
recommended INN2 in accordance with the “Procedure for the selection of Recommended
International Nonproprietary Names for Pharmaceutical substances”.3 However, the
recommended INN “upifitamab” has been considered evocative of an inappropriate and vulgar
Swedish phrase due to the presence of the prefix upifita-.
At its meeting of 18–21 November 2022, the INN Expert Group decided that, prior to
consideration of the above-mentioned proposal, Member States should be requested to provide
their comments on: (i) a possible change of the recommended INN “upifitamab” and
“upifitamab rilsodotin” and (ii) its substitution by the names upinitatug and upinitatug
rilsodotin, in accordance with the article 9 of INN Procedure. The INN Expert Group agreed that
this is an extraordinary circumstance and this offensive connotation in Sweden, Norway,
Denmark and Swedish-speaking parts of Finland should be avoided, in particular because the
substance is being evaluated as a potential treatment of ovarian cancer. Moreover, the
recommended INN “upifitamab” and “upifitamab rilsodotin” is not yet marketed and the INN
applicant developing it has agreed to this substitution. In addition to the change of the prefix, the
stem -tug for “unmodified immunoglobulins” has been selected in accordance with the new
nomenclature scheme for naming monoclonal antibodies.4
1
WHO Drug Information, Vol. 34, No. 3, 2020 Recommended INN: List 84.
2
WHO Drug Information, Vol. 35, No. 1, 2021 Recommended INN: List 85.
3
INN Revised Procedure.
4
Available at: New INN monoclonal antibody (mAb) nomenclature scheme (May 2022) (who.int).
Page 2
C.L.5.23
The chemical names and graphic formulae of the recommended INN “upifitamab” and
“upifitamab rilsodotin” are as follows:
upifitamab
immunoglobulin G1-kappa, anti-[Homo sapiens SLC34A2 (solute carrier family 34
(sodium phosphate) member 2, sodium/phosphate cotransporter 2B, NaPi2b, NaPi3b)],
monoclonal antibody;
gamma1 heavy chain (1-449) [VH (Homo sapiens IGHV1-46*01 (81.6%) -(IGHD) -IGHJ4*01
(92.9%)) [8.8.12] (1-119) -glycyl (120) -Homo sapiens IGHG1*03, G1m3, nG1m1 (CH1 R120
(217) (121-218), hinge 1-15 (219-233), CH2 (234-343), CH3 E12 (359), M14 (361) (344-448),
CHS K>del (449)) (121-449)], (223-215')-disulfide with kappa light chain (1'-215') [V-KAPPA
(Mus musculus IGKV10-94*01 (84.2%) -IGKJ5*01 (91.7%)/Homo sapiens IGKV1-16*01
(83.2%) -IGKJ2*01 (90.9%)) [6.3.9] (1'-107') -arginyl (108') -Homo sapiens IGKC*01 (100%)
Km3 A45.1 (154), V101 (192) (109'-215')];
dimer (229-229”:232-232”)-bisdisulfide, produced in Chinese hamster ovary (CHO) cells,
glycoform alfa
Page 3
C.L.5.23
upifitamab rilsodotin
immunoglobulin G1-kappa, anti-[Homo sapiens SLC34A2 (solute carrier family 34
sodium phosphate member 2, sodium/phosphate cotransporter 2B, NaPi2b, NaPi3b, NAPI-3B)],
monoclonal antibody, conjugated, via a thioether bond, to3 to 5 flexible polymers PHF-BA-EG2-
MI-AF-HPA-Ala, each comprising maleimide (MI) bioconjugation linkers and 3 to 4 auristatin
F- hydroxypropylamide-L-alanine (AF-HPA-Ala), with a drug ratio of 12:1 to 15:1;
gamma1 heavy chain (1-449) [VH (Homo sapiens IGHV1-46*01 (81.6%) -(IGHD) -IGHJ4*01
(92.9%)) CDR-IMGT [8.8.12] (26-33.51-58.97-108) (1-119) -glycinyl (120) -Homo sapiens
IGHG1*03 (100%), G1m3, nG1m1 (CH1 R120 (217) (121-218), hinge 1-15 (219-233), CH2
(234-343), CH3 E12 (359), M14 (361) (344-448), CHS K>del (449)) (121-449)], (223-215')-
disulfide with kappa light chain (1'-215') [V-KAPPA (Mus musculus IGKV10-94*01 (84.2%) -
IGKJ5*01 (91.7%)/Homo sapiens IGKV1-33*01 (83.2%) -IGKJ2*01 (90.9%)) CDR-IMGT
[6.3.9] (27-32.50-52.89-97) (1'-107') -arginyl (108') -Homo sapiens IGKC*01 (100%) Km3
A45.1 (154), V101 (192) (109''-215')]; dimer (229-229":232-232")-bisdisulfide, produced in
Chinese hamster ovary (CHO) cells, glycoform alfa; conjugated, via a thioether bond, from 3 to
5 flexible biodegradable polymers, poly(1-hydroxymethylethylene hydroxymethyl-formal)
(PHF)-BA-EG2-MI-AF-HPA-Ala, each comprising maleimide (MI) conjugation linkers and 3 to
4 cytotoxic auristatin F- hydroxypropylamide-L-alanine (AF-HPA-Ala), with a drug ratio of 12:1
to 15:1
Page 4
C.L.5.23
Page 5
C.L.5.23
In the light of the above, the World Health Organization hereby requests Member States to
provide their comments on this proposal, including with regard to any conflicts (or potential
confusion) with other names, possible implications for the safety of patients and/or any other
drug regulatory issues. The Organization should like to draw attention to the fact that this request
for comments is being made on an informal basis and should not be considered as a notice of a
proposed INN pursuant to article 3 of the above-mentioned Procedure.
The Organization would appreciate receiving any comments as aforesaid by 19 May 2023.
They should be directed to the INN Programme, c/o Health Products Policy and Standards
Department (HPS/MHP), World Health Organization, Avenue Appia 20, CH -1211
Geneva 27, Switzerland, e-mail:
[email protected].
GENEVA, 24 February 2023