Do you need consultation on the classification of biological active substances? Are you familiar with the documentation requirements? Do you need help in writing the documentation?

1. Biological Active Substances
3.2.2015
DRA Consulting Oy
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2. Biological Active Substance
• Substance that is produced by or extracted from a biological
source, such as
• micro-organisms, organs and tissues of either plant or animal origin,
• cells or fluids of human or animal origin,
• and biotechnological cell constructs
• and for which a combination of physico-chemical-biological
testing and the production process and its control is needed for
its characterisation and the determination of its quality
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3. Classification
1. Traditional
• Vaccines, blood components, allergenics, extracted proteins and
carbohydrates etc.
2. Biotechnological
• Proteins produced by recombinant DNA technology
3. Advanced therapy
• Cell and gene therapy, tissue engineering
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4. List of biological active substances of non-
recombinant origin
• List of biological active substances/biological medicinal
products that do not belong to one of the categories that
are already considered as biological active
substances/biological medicinal products by default in the
current legislation is published by HMA webpages
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5. Differences: chemical vs. biological
5
Revers L. & Furczon E. (2010) An introduction to biologics and biosimilars. Part I: Biologics: What are
they and where do they come from? Can. Pharm. J. 143: 134

6. 6
Chemical Biological
Small Very large
Simple Complex molecule or mixture
of molecules
Stable Unstable
Manufactured by a predictable
chemical synthesis
Manufactured in a living system
sensitive to changes in the
manufacturing process
Well-defined chemical structure Characterisation difficult
Possible to produce identical
copy
Impossible to produce identical
copy
Immunogenicity

7. EU Regulation on Biologicals
• Directives
• Regulations
• Notice to Applicants
• Scientific Guidelines
• GMP guidelines
• European Pharmacopoeia
Do not hesitate to contact us for consultation on the
requirements.
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8. Applications for biological medicinal products
• Due to complexity of biologicals
• Not possible to use the Active Substance Master File (ASMF)
procedure
• Complete applications (2001/83/EC Articla 8(3))
• For new API
• Quality, pre-clinical and clinical data
• Bibliographic applications (2001/83/EC Articla 10a)
• Normally not applicable for biological products
• Abridged applications (2001/83/EC Articla 10 (4))
• For biosimilar products
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9. Variations in EU
• CmDh Q&A: ”with regard to variations, specific conditions apply
for biological medicinal products because of their complexity”
• Classification of variations
• Biologicals typically Type IB/II vs. chemical APIs and conventional
products Type IA/IB
• Documentation requirements
• Batch data required from 3 production scale batches of biologicals vs.
2 batches for chemical APIs and conventional products

10. Biosimilar
= A biological medicinal product that contains a version of the
active substance of an already authorised original biological
medicinal product (reference medicinal product) in the EEA
• Due to the nature and manufacturing methods of biomolecules,
totally identical structure cannot be achieved
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11. MA application – specific requirements for
biosimilar products in EU
• Module 1
• Module 2
• Module 3
• In addition to full Module 3, a demonstration of comparability is
required
• The detailed location of this data within the CTD structure can be
discussed with the EMA prior to submission, but it is recommended to
make use of section 3.2.R.
• 3.2.A
• 3.2.R
• Module 4 and 5
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12. • Do you need consultation on the classification?
• Are you familiar with the documentation requirements?
• Do you need help in writing the documentation?
• Look no further, we have a team of specialists ready for
you!
www.dra.fi
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