Biosimilars Flashcards
define what a biologic drug is
a drug coming from a biological origin
what are some features of biologic drugs
big size, significant microheterogeniety, very specific (have a specific biological target), complex structure
what is a biosimilar
it is a product that is similar to the original biologic drug. Some can be used interchangeably. similar but not identical
define microheterogeneity
Slight differences in structure between essentially identical molecules, e.g., in the saccharide portion of a glycoprotein.
are biosimilars bioequivalent in the same way as generic drugs?
No. They have minor differences but are highly similar. This means studies must take place to decide which biological drugs are interchangeable based upon the similarities in the structure, function, pharmacokinetics, pharmacodynamics, efficacy and safety.
what are the development stages of a biosimilar
development, pre-clinical, Phase 1, Phase 3
discovery has already taken place - the discovery of biologic
phase 2 can be skipped as this assesses efficacy and safety
name 4 advantages of biosimilars
Lower cost: Biosimilars help reduce healthcare costs.
Increased access and choice: More patients can access biologic treatments.
Encourages innovation: Competition drives further development.
Market growth: Biotechnology medications are expected to dominate the pharmaceutical industry
name 3 disadvantages of biosimilars
Complexity and process specificity: Biosimilars are more complex to manufacture than small-molecule generics.
Regulatory challenges: Strict requirements for demonstrating similarity to the reference biologic, including safety, efficacy, and immunogenicity (risk of immune response).
Bioanalytic and comparability challenges: Defining biological activity and ensuring global standards for approval and commercialization.
What needs to be established for a drug to be considered a biosimilar?
Similarity to reference product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise.
Why can biosimilars not be considered identical?
Minor natural variations due to the way biologics are produced in living cells.
Why does the cost of biologics and biosimilars remain high?
New indication requires new patent, changes in manufacturing process- prove equivalence.
Describe the 6 steps taken to develop a biologic
- Choice of Sequence (Green)
This is the selection of the gene encoding the desired protein (e.g., human erythropoietin (EPO)).
The correct sequence ensures proper protein folding and function. - Cloning (Green)
The selected gene is inserted into a vector (e.g., a plasmid).
This vector is introduced into a host cell for protein production. - Expression in Host Cell (Red)
The host cell (e.g., Chinese Hamster Ovary (CHO) cells or E. coli) expresses the protein.
CHO cells produce glycosylated EPO (required for function).
E. coli produces a non-glycosylated version, which may not be fully functional. - Fermentation (Red)
The host cells are grown in large bioreactors (fermentation tanks).
Tank size affects glycosylation, impacting protein structure and activity. - Purification (Red)
The produced protein is extracted and purified.
Eprex Example: Originally, human serum albumin was used as a stabilizer.
In 1998, the EU required its removal due to concerns about disease transmission.
Changes in formulation led to purely recombinant EPO, but this also resulted in reports of antibody-mediated pure red cell aplasia (PRCA) in some patients. - Formulation (Red)
The final product is prepared for storage and administration.
It includes stabilizers and preservatives to ensure shelf-life.
For Eprex, changes in formulation (removal of albumin) were linked to increased immunogenicity, causing unexpected side effects.
Why does the whole production process of biosimilars and biologics need to be accurately described
A change in a tiny thing may have severe consequences for the patient
what is erythropoietin
EPO (erythropoietin) is a glycoprotein hormone that stimulates the production of red blood cells (erythropoiesis) in the bone marrow. It is naturally produced by the kidneys in response to low oxygen levels in the blood.
3 MAIN FUNTIONS
how dies erythropoietin (EPO) work
1. Oxygen Sensing in the Kidneys
Specialized peritubular cells in the kidneys detect low oxygen levels.
In response, these cells increase EPO production.
EPO is released into the bloodstream and travels to the bone marrow.
2. Stimulation of Red Blood Cell Production
EPO binds to erythropoietin receptors (EPOR) on erythroid progenitor cells in the bone marrow.
This triggers cell survival and proliferation signals, preventing these cells from dying.
The progenitor cells mature into red blood cells (erythrocytes).
3. Increased Oxygen Delivery
As more red blood cells are produced, oxygen-carrying capacity improves.
The kidneys reduce EPO production once oxygen levels return to normal.
what are some uses of recombinant EPO
Recombinant EPO is a biological drug used:
- anaemia in CKD
- chemotherapy-induced anaemia
- drug-related anaemia in HIV
- Pre-blood transfusion was used to boost RBC levels.
Why was Eprex removed from use
The small modification in the structure led to aplasia (red blood cell death), leading to anaemia in patients. Patients developed antibodies to the drug due to it being given subcutaneously. The immune system produced antibodies that targeted endogenous EPO leading to PRBA (pure red blood cell aplasia) anaemia. However, this was not the case with IV administration.
The risks outweighed the benefits, and so it was removed.
What is eprex
synthetic EPO is used to treat anemia
what are some of the challenges associated with the manufacture and formulation of EPO
Post-translational modifications such as glycosylation can result in loss of efficacy or have negative impacts on pharmacokinetic properties
what is a generic
a copy of a chemical drug. There is no difference in the structure. They are identical
why is there a price difference between insulin in the US and UK
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Price Regulation:
- UK: NHS negotiates lower drug prices.
- US: No single-payer system; companies set prices.
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Patent Tactics:
- US: Evergreening extends patents and keeps prices high.
- UK: Faster adoption of biosimilar insulins.
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Insurance Costs:
- US: Prices vary; uninsured pay full price (hundreds per vial).
- UK: Insulin-free or fixed charge (£9.65 in 2024) under NHS.
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Pricing Strategies:
- US: No price controls; profit maximization.
- UK: Controlled pricing via Voluntary Scheme for Branded Medicines Pricing and Access (VPAS) to prevent hikes.
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Middlemen:
- US: PBMs inflate costs through negotiations and fees.
- UK: No PBMs, fewer cost layers.
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US Reforms:
- Inflation Reduction Act (2022): Caps insulin at $35/month for Medicare.
- Major manufacturers announced price cuts.
