introduction to biological active substances
TRANSCRIPT
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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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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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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Differences: chemical vs. biological
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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
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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
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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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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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
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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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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• 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!
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