2009-12-30-世界卫生组织-INN_Bio_Review_2010_60页_350kb

Summary of International Nonproprietary Names (INN) for Biological and Biotechnological Substances

Core Content

The World Health Organization (WHO) established the International Nonproprietary Name (INN) system in the 1950s to provide a unique, non-proprietary name for medicinal substances. This system has been extended to biological and biotechnological substances to ensure global recognition and clarity in naming. The document provides a review of the current INN naming conventions, policies, and assigned names for various categories of biological and biotechnological products.

Main Viewpoints

• INN Purpose: To ensure a unique, globally recognized name for biological and biotechnological substances, without proprietary rights.
• Pharmacological Classification: Substances are grouped based on their pharmacological function and biological origin.
• Naming Systems: A systematic approach is used with stems, pre-stems, and schemes to distinguish between different types of products.
• Flexibility and Updates: The INN system is adaptable to new developments and will be regularly updated to reflect new products and naming policies.

Key Information

1. Pharmacological Classification

• Alimentary tract and metabolism: Insulins
• Anti-infectives: Antimicrobial polypeptides, human papilloma virus
• Antineoplastics: Peptide vaccines, toxins
• Blood and agents acting on the haemopoietic system: Antithrombins, blood coagulation cascade inhibitors, blood coagulation factors, erythropoietin type blood factors
• Immunomodulators and immunostimulants: Colony stimulating factors, interferons, interleukin receptor antagonists, interleukin type substances, monoclonal antibodies, receptor molecules
• Hormones, hormone antagonists, hormone-release peptides: Growth hormone derivatives, oxytocin derivatives, etc.
• Various: Antisense oligonucleotides, enzymes, gene therapy products, growth factors, skin substitutes, transgenic products, vaccines

2. Current Status of Stems and Systems

Groups with respective stems:

• Antisense oligonucleotides: -ryn
• Blood coagulation cascade inhibitors: -cogin
• Blood coagulation factors: -cog
• Colony stimulating factors: -stim
• Enzymes: -ase
• Erythropoietin type blood factors: -poetin
• Growth factors: -ermin
• Heparin derivatives: -parin
• Hirudin derivatives: -irudin
• Pituitary hormone-release inhibiting peptides: -relix
• Interleukin receptor antagonists: -kinra
• Interleukin type substances: -kin
• Monoclonal antibodies: -mab
• Oxytocin derivatives: -tocin
• Peptides and glycopeptides: -tide
• Pituitary hormone-release stimulating peptides: -relin
• Receptor molecules: -cept
• Synthetic polypeptides with corticotropin-like action: -actide
• Vasoconstrictors, vasopressin derivatives: -pressin

Groups with respective pre-stems:

• Antimicrobial, bactericidal permeability increasing polypeptides: -ganan

Groups with INN schemes:

• Antithrombins
• Gene therapy products
• Insulins
• Interferons
• Pituitary / placental glycoprotein hormones

Groups without stems or INN schemes:

• Growth hormone antagonists
• Human papilloma virus
• Peptide vaccines / recombinant vaccines
• Thrombomodulins
• Toxins

3. General Policies

Blood Products:

• Natural human blood products do not have INNs.
• Recombinant versions should have distinctive names reflecting established names.
• "Activated" should be included in names for activated forms.

Fusion Proteins:

• If a stem exists for either part of the fusion, it should be included in the name.
• Indication of being a fusion product is not necessary in the name at present.

Gene Therapy Products:

• A two-word naming scheme is used, with a prefix (gene component), infix (gene function), and suffix (vector type).
• For naked DNA, only one word is needed.

Glycosylated Compounds:

• Glycoproteins / glycopeptides: Identified with a stem and Greek letters for glycosylation differences.
• Subgroups are identified with Greek letters and Arabic numbers for amino acid sequence differences.
• Small letters are used to distinguish different compounds with similar sequences.

Immunoglobulins:

• No INN is assigned for each immunoglobulin.
• Systematic or descriptive names are used instead.

Monoclonal Antibodies:

• INNs are composed of a prefix, substem A (target class), substem B (species origin), and a suffix.
• Substem B includes: a (rat), e (hamster), i (primate), o (mouse), u (human), xi (chimeric), zu (humanized).
• Substem A includes: -b (bacterial), -c (cardiovascular), -f (fungal), -k (interleukin), -l (immunomodulating), -n (neural), -s (bone), -t (toxin), -v (viral).
• If substem B starts with a consonant, a vowel is added to avoid pronunciation issues.

Non-glycosylated Compounds:

• Identified with a stem or a word, with a random prefix to denote differences.
• Examples include hirudin analogues and insulin variants.

Skin Substitutes:

• Considered engineered tissue, so they fall outside the INN system.

Transgenic Products:

• If an INN already exists, it should be used with a qualifier to indicate transgenic origin.
• The source of the substance should be included in the INN definition.

Vaccines:

• Not included in the INN system but named by the Expert Committee on Biological Standardization.
• Recombinant vaccines require detailed information for INN application.
• Live viruses are not named; instead, peptide vaccines are used, which are chemically well-defined and easier to name.

4. Summary of Assigned INNs

• Antimicrobial, bactericidal permeability increasing polypeptides: iseganan, omiganan, pexiganan
• Antisense oligonucleotides: afovirsen, aganirsen, alicaforsen, etc.
• Antithrombins: antithrombin III, antithrombin alfa
• Blood coagulation cascade inhibitors: drotrecogin alfa (activated), taneptacogin alfa, tifacogin
• Blood coagulation factors: eptacog alfa (activated), octocog alfa, nonacog alfa, tridecagog, vonicog alfa
• Colony stimulating factors: ancesstim, garnocestim, romiplostim, lerdistim, milodistim, filgrastim, lenograstim, etc.
• Enzymes: brinase, kallidinogenase, ocrase, pegaspargase, rasburicase, etc.
• Erythropoietin type blood factors: darbepoetin alfa, epoetin alfa, beta, gamma, etc.
• Gene therapy products: alferminogene tadenovec, alipogene tiparvovec, amolimogene bepiplasmid, etc.
• Growth factors: ancesstim, telbermin, murodermin, ersofermin, etc.

5. Current Challenges

• The increasing complexity and diversity of biological and biotechnological substances require continuous review and updates to the INN system.
• The need to differentiate between similar products, such as recombinant glycosylated proteins and their variants, remains a challenge.
• New technologies, such as gene therapy and peptide vaccines, are introducing products that may not fit into existing naming schemes.

6. Conclusion

This document serves as a living review of the INN system for biological and biotechnological substances, summarizing the naming policies and assigned names. It is regularly updated to reflect new scientific developments and ensure that the naming system remains relevant and effective for global pharmaceutical communication and regulatory purposes.