W7 Biologicals and Biosimilars (GP) Flashcards
What are biological drugs?
What are examples? (6)
Applications? (4)
- Biologics are any pharmaceutical drug product manufactured in, extracted
from, or semisynthesized from biological sources. - The first biologic drug approved in 1982 (humanised insulin)
- Different types of biologicals:
o peptides
o proteins
o antibodies (e.g. DPT vaccines)
o nucleic acids (e.g. RNA-vaccines)
o cell-based therapies
o carbohydrates - Applications: cancer, rheumatoid arthritis
inflammatory bowel disease, infectious disease
Chemical vs Biological drug:
Weight, structure, source?
Stability, Immunogenicity?
- Low Molecular weight (180 Dalton)
- Simple, well defined
- By Chemical synthesis (1st, 2nd, 3rd structure)
- Usually stable
- Usually unexpected
- High Molecular weight (150k Dalton)
- Complex
- Made or derived from a biological source
- Sensitive to handling and storage conditions
- Higher potential
What are the Various expression systems for producing Biologicals? (4)
- Prokaryotes - Escherichia coli
- Yeast strains - Saccharomyces cerevisiae, Hansenulla polymorpha and Pichia pastoris
- Transgenic plants (tobacco, cereals, legumes, fruits, and vegetables)
- Mammalian cells- best option
In order of complexity, cost, time, high quality:
From biologicals to biosimilars
- Manufacturing process of these products are often covered by Intellectual Property (IP)
- After this is expired, other companies can use the same process to prepare a version of the product
- These are called biosimilars or follow-up proteins (mainly in US)
- Compared to the reference or originator product
What is the defintion of a biosimilar?
A new biological product that has been developed to be similar to an existing biological product (“reference” or “originator”)
A biosimilar medicine is a biological medicine which has been shown not to have any clinically meaningful differences from the originator medicine in terms of quality,
safety and efficacy.
Concept of similarity: (3)
- The nature of biological drugs and their manufacturing process leads to unique attributes in the product being produced
- Manufacturing conditions (e.g., medium batch, manufacturing sites, pH)
-
Post-translational modifications (e.g., glycosylation)
(Example: Bacterial cells do not have the ability to perform complex posttranslational modifications including glycosylation which will affect the folding of the protein.) -
Amino acid sequence e.g. Plant derived products
-In eukaryotic cells, there are 20 a.a both essential and nonessential, some essential a.a are missing in plant-derived products
Biosimilars nomenclature:
- ‘Core name’ + suffix
rituximab
rituximab-pvvr
rituximab-abbs - Suffix: 4 letter, lower case, no recognizable
meaning - Totally different names from reference
product (pharmaceutical companies) - Identify reference/biosimilar relationship
oTherapeutic category
o Dosing - Differentiate products
o Accurate product identification
o Prevent inadvertent substitution - Trackability of adverse reactions
Biosimilars approval
Who are the 2 regulatory bodies?
- Different regulatory bodies (EMA-European Medicines Agency, FDA-Food and Drug Administration)
- First approved biosimilar - Somatropin (Omnitrope® - 2006), in Germany (EU)
Approval process:
What must a manufacturer demonstrate for a medicine to be approved?
- The MHRA (Medicines and Healthcare products Regulatory Agency) outlines guidance on the licensing of biosimilar products in the UK
- MHRA is closely working with EMA (European Medicines Agency)
- Same standards of pharmaceutical quality, safety and efficacy that apply to all biologics.
-
For a biosimilar medicine to be approved, the manufacturer must demonstrate that the biosimilar has no clinically meaningful differences in safety and efficacy from the
reference medicine (abbreviated pathways)
Approval process:
Biosimilar products must present a complete characterisation of the molecules as compared to the innovator.
This includes:
* Primary structures (amino acid composition)
* Higher order structures (secondary,
tertiary and quaternary structures)
* Post-translational modifications
* Intentional chemical modifications (e.g.,
* PEGylation sites, protein deamination and oxidation
Biosimilars market (for info)
- Number of Biosimilar medicines is increasing over the years
- Growing global market (10% of sales)
What are the Impact of biosimilars? (benefits)
- Reduced time drug development
- Reduced costs of drug development
- Final cost of the final product
- More options available
o for affordability (chronic diseases)
o loss of clinical efficacy over time
(e.g., antibody biosimilars)
Biosimilar applications? (6)
When are they used:
- Auto-immune diseases
- Blood disorders
- Diabetes
- Oncology
- Growth Deficiency
- Female infertility
Insulin as a biological:
- Insulin is produced by the pancreas
- Insulin injections are needed for Type 1 diabetes therapy
- Initially purified from bovine or porcine pancreas
- Biosynthetic human insulin
- Produced by recombinant DNA technology
- Humulin, the first ever biological (1982)
- Insulin is a small globular protein containing two chains, A (21 residues) and B (30 residues)
- Disulfide bonds between cysteine residues help stabilising the structure of the protein
Ways to produce/obtain insulin?
- Recombinant DNA technology via individual chains (A) or proinsulin (B)
- Mostly E. coli (bacteria) and Saccharomyces cerevisiae (yeast)
- Plant-based approach (oilseeds of plant Arabidopsis thaliana)
