Dr R. Balocco Mattavelli, INN/TSN/RHT WHO Technical Briefing Seminar on Essential Medicines and Health Products Geneva, 3-7 November 2014 International

Dr R. Balocco Mattavelli, INN/TSN/RHTWHO Technical Briefing Seminar on Essential Medicines and Health ProductsGeneva, 3-7 November 2014

International Nonproprietary NamesInternational Nonproprietary Names


What's in a name?What's in a name?Safety

Quality

Information

RegulationRational use use

Procurement

Efficacy


Verba volant scripta manentVerba volant scripta manent

"By assigning a single international name to drugs, WHO helps ensure that a prescription filled abroad is what doctor ordered back home."

Dr Margaret Chan, Director General


The WHO International Nonproprietary Name (INN) Programme

The WHO International Nonproprietary Name (INN) Programme

To provide one single name worldwide for active pharmaceutical substances

Initiated in 1950 by resolution WHA3.11

Operational since 1953

Based on WHO Constitution


INN ProgrammeINN Programme

Mandated by the Member States in 1953

One of the oldest WHO programmes

To devise a single name for a substance

INNs are recognized in almost all Member States

INNs can be used freely and cannot be registered as trade names

Not concerned with formulations


Interested parties outside WHOInterested parties outside WHO

USAN Program

Pharmacopoeias(BP, FP, USP, JP….)

European Commission, WCO, WIPO, …

Research based industry

National trade-mark authorities

DRAs(EMEA, US-FDA….)

INN Programme


Various trade names ® for one substance, ex. paracetamol

Various trade names ® for one substance, ex. paracetamol


Various generic names for one substance, ex. paracetamol

Various generic names for one substance, ex. paracetamol


One International Nonproprietary Name for one substance, ex. paracetamol

One International Nonproprietary Name for one substance, ex. paracetamol


INNs…INNs…

Unique name

Distinctive in sound and spelling

Not liable to confusion with other names in common use

Formally placed by WHO in the public domain

Can be used without any restriction to identify pharmaceutical substances


The INN SystemThe INN System

WHO Secretariat

INN Expert Group

INN Advisory Group on Biological

Publications


The Business Process ModelThe Business Process Model

Broad consultation

Lot of correspondence

2 INN meetings/year

"Ad hoc" meetings

……


INN On Line ApplicationINN On Line Application

• Automatic Data Entry

• Data Validation

• Confidential Communication

• Electronic format for structures


Reaching the worldReaching the world

INNs Lists are published in WHO Drug Information

All INNs are published in a Cumulative List

On-line INN information: Mednet - INN Extranet

Global Data Hub


INN List in practiceINN List in practice

peginterferonum beta-1a # (108)

peginterferon beta-1a N2.1-{(2RS)-2-methyl-3-[ω-methoxypoly(oxyethylene)]propyl}human interferon beta (fibroblast interferon, IFN-beta) glycosylated expressed in mammalian cellsimmunomodulator

péginterféron bêta-1a N2.1-{(2RS)-2-méthyl-3-[ω-méthoxypoly(oxyéthylène)]propyl}interféron bêta humain (interféron fibroblastoïde, IFN-bêta) glycosylé produit par les cellules de mammifèresimmunomodulateur

peginterferón beta-1a N2.1-{(2RS)-2-metil-3-[ω-metoxipoli(oxietileno)]propil}interferón beta humano (interferón fibroblastoide, IFN-beta) glicosilado producido por las células de mamíferoinmunomodulador

C913H1417N246O256PS7 [C2H4O]n 1211327-92-2

H3CO

O NH

CO2H

H

S

CH3

nH CH3

*

and epimer at C*et l'épimère en C*y el epímero al C*

H2N CO2H

H

O P

O

OHOH

Sequence / Séquence / SecuenciaMSYNLLGFLQ RSSNFQCQKL LWQLNGRLEY CLKDRMNFDI PEEIKQLQQF 50QKEDAALTIY EMLQNIFAIF RQDSSSTGWN ETIVENLLAN VYHQINHLKT 100VLEEKLEKED FTRGKLMSSL HLKRYYGRIL HYLKAKEYSH CAWTIVRVEI 150LRNFYFINRL TGYLRN 166

Disulfide bridge location / Position du pont disulfure / Posicion del puente disulfuro31-141

Modified residues / Résidus modifiés / Restos modificados

M1

N-pegMet

S119

O-phosphonoSer

Glycosylation site (N) / Site de glycosylation (N) / Posicion de glicosilación (N)Asn-80


MedNetMedNet

https://mednet-communities.net/inn/


INN for a global data hubINN for a global data hub

Software Company Pharmaceutical Industry

BPh

IMGT

SIB-University of

Geneva

DRAs

ANSM

WIPO FDA

VIDAL

USP

National Authorities and various organizations

INN


Use of stemsUse of stems

To indicate chemical and /or pharmacological group relationship

Published for 'established series of related compounds'

INN and stems have protection within trade mark arena

WHO publication "The use of stems in the selection of INN " Stem book 2013

pre-stems list

Names of "pharmacologically/chemically -related" substances have a common stem


How long…? How long…?

59 names

30% biologicals

12.5 months as an average

Nearly 95% pub. after 1 or 2 rounds of discussion


Biologicals are more complexBiologicals are more complex

Interferon beta

MW 19'000D

Aspirin

MW 180D


Naming Biosimilars?Naming Biosimilars?

As Biosimilars are Biologicals, they should be named as Biologicals

But if Biosimilars & Innovator biologicals are given the same INN, a mean to distinguish/ identify is needed (e.g trade name)


Some Problems with BiosimilarsSome Problems with Biosimilars

A regulatory route may or may not exist

The same substance (product) may be viewed as biosimilar in some jurisdictions but not others

Separate national solutions have been adopted

No INN specific policy for biosimilars currently exists

Some DRAs have requested WHO to develop an identification system applicable to biosimilars


INN a global name?INN a global name?

epoetin alfa (2x)epoetin zeta epoetin kappa

)generic recombination(epoetin alfa biosimilar 1

epoetin lambda


…………

This is an issue that does need to be

addressed globally, and soon

The WHO INN Programme has a clear

mandate

The need for a harmonized (global) system is crucial


Biological Qualifier scheme Biological Qualifier scheme

All biological substances that are assigned INN should:

1.Be clearly identified

2.Have the INN of the reference product as the first part

of the name

3.Have parallel nomenclature scheme (Biological

Qualifier) that uniquely identifies the substance


Biological Qualifier DatabaseBiological Qualifier Database

INN Secretariat manages a secure databaseApplicant for a code submits online and follow

progressDRAs: validate data and have unrestricted

access to information in databaseManufacturers/applicants/industry: what

restrictions if any?‘Public’: INN website lists codes and INN (and

products?



INN is simpleINN is simple

"Simplicity is the ultimate sophistication"

Leonardo Da Vinci


Thank youThank you

Grazie! Merci! Obrigado ! Gracias 谢谢！ありがう！ ARIGATOU ！ Danke! Dziękuję! Dank je / u! Mulţumesc! Teşekkür ederim! Tack!Tack så mycket Grazie!

Kiitos! תודה לך! Takk! ďakujem, ďakujem vám ; Hvala! Dشكرًا!shokran Ευχαριστώ! 감사합니다 Děkuji! Tak skal du have! Dankon! Hvala, Hvala lepa, Najlepša hvala

Gràcies! Faleminderit Hvala! Ačiū, De’koju, Labai ačiū ขอบคุ�ณ ; ขอบคุ�ณมาก(khàwp khun) ; (khàwp khun mâak) shukrīya (بہت) شكريه (bahut) Cảm ơn cô ; Cảm ơn cô nhiều;

Благодаря!Благодаря! Obrigado!” Gracias Þakka þér! baie dankie ; Takk fyri! Sipas dekem متشکرم! Благодарам! Hvala Vam! V Təşəkkür Paldies!Pateicos! /

Tencinu! Terima kasih Дуже дякую ;Дякую ; Спасибі! Баярлалаа ; Гялайлаа ; Танд их баярлалаа Terima kasih ধন্য�বা�দ (dhonyobād) Salamat! Trugarez ! Mersi !

Trugarez Danke!

Documents

Dr R. Balocco Mattavelli, INN/TSN/RHT WHO Technical Briefing Seminar on Essential Medicines and Health Products Geneva, 3-7 November 2014 International