Biosimilars Flashcards
What are biotech drugs?
a medication derived from a living organism or their cells
How are biotech drugs produced?
biotechnology
-technology that harnesses living organisms and biomolecular processes to develop fight diseases
True or false: biotech drugs are smaller and less complex than traditional pharmaceutical products
false
biotech drugs are larger and more complex
What are the steps in manufacturing of biological products?
- host cell development
- master cell bank establishment
- protein production
- protein purification
- analysis
- formulation
- storage & handling
Differentiate biologics and small molecule pharmaceuticals based on the following:
-method of synthesis
-molecular size
-structure
-susceptibility to contamination
-molecular structures
-complexity
-sensitivity to physical factors
method of synthesis
-small molecule: chemical synthesis
-biologics: genetically engineering cells/organisms
molecular size
-small molecule: small
-biologics: large
structure
-small molecule: usually fully known
-biologics: complex, frequently partially unknown
susceptibility to contamination
-small molecule: low
-biologics: high
molecular structure
-small molecule: relatively simple
-biologics: complex spatial structures
complexity
-small molecule: relatively pure ingredients
-biologics: complex ingredients
sensitivity to physical factors
-small molecule: low
-biologics: higher
Differentiate biologics and small molecule pharmaceuticals based on the following:
-clinical behavior
-manufacturing process
-species
-immunogenicity
-ADME
-PK profile
-half life
-safety
clinical behavior
-small molecule: well understood MOA
-biologics: complicated MOA, not always understood
manufacturing process
-small molecule: straightforward
-biologics: highly complex
species
-small molecule: interdependent
-biologics: specific
immunogenicity:
-small molecule: non antigenic (generally)
-biologics: antigenic
ADME
-small molecule: faster absorption, higher distribution, metabolized to non-active and active metabolites, excretion rarely target-mediated
-biologics: slower absorption, distribution low, catabolized to endogenous amino acids, excretion often target-mediated
PK profile
-small molecule: frequently linear
-biologics: usually non-linear
half-life
-small molecule: short(er)
-biologics: long
sagety
-small molecule: toxicity (variable mechanisms)
-biologics: exaggerated pharmacology
Provide some points regarding the regulation of biologics.
before consideration for approval there must evidence to show safety, efficacy, and quality
must include more detailed chemistry and manufacturing information (differs from other drugs)
-important for purity
as part of NDS process, the manufactures must supply Product Specific Facility Information
On-Site Evaluation (OSE) assess production process and facility
if evidence supports product the product is issued a NOC and DIN
products are carefully scrutinized before they are placed in any lvl of the lot release process
Health Canada monitors AE, complaints, and reports (post approval surveillance)
What are some types of biologics?
blood and blood components
proteins
human tissues
vaccines
allergenic extracts
cellular & gene therapies
Provide a brief history of biologics.
1982: first biologic (rDNA insulin)
between 1996-2007: 136 biologics FDA approved
today: >350 commerically available
Which type of biologic accounts for a huge portion of available biologics?
monoclonal antibodies
-direct attack on site
What is the top target for monoclonal antibodies?
oncology
-PD1/PDL1
Describe monoclonal antibodies for COVID-19.
used in early treatment of mild-moderate COVID-19 illness in at risk patients
provide an immune response (act like natural antibodies)
examples:
-regeneron
-bamlanivimab
-etesevimab
-sotrovimab
-evushield
Are the estimates for cost of biologics fairly correct?
history tells us that predictions are vastly underestimated
Who is the top pharma company by revenue as of 2022?
Pfizer ($100 billion)
-vaccine is a big reason
What are the steps in the biopharmaceutical research and development process?
basic research
drug discovery
pre-clinical
clinical trials
-phase 1, phase 2, phase 3
FDA review
post-approval research & monitoring
-phase 4
What are some reasons that less new drugs are launched in Canada compared to countries like that USA and European countries?
difference in market size
didnt do well in those markets
lots of “me too” drugs
Which indication sees the largest number of biotech products?
oncology
Why are biologics so expensive?
manufacturing costs
R&D costs
competition (free market and benchmark pricing)
many target rare diseases=small market
What are intellectual property rights?
provides market exclusivity
-period of time during which competing firms may not use the innovative firms clinical trial data to obtain marketing authorization for a generic version
gives incentives to invest in the difficult and expensive R&D necessary for biologics advances
What are some future issues for biologics?
market exclusivity will erode as patents expire and competing products enter the market
revenues generated by biologics are threatened by increasing scrutiny from government health agencies and other payers
What is a biosimilar?
a “copy” of a commercially available biopharmaceutical (refence product) that no longer is protected by patent
-has undergone rigorous analytical and clinical assessment in comparison to the reference product
-approved by a regulatory agency according to a specific pathway for biosimilar evaluation
highly similar to its reference product in PC, efficacy, and safety
True or false: Health Canada approval of a biosimilar is a declaration of pharmaceutical equivalence, bioequivalence or clinical equivalence to its reference biologic drug
false
What are the potential benefits of biosimilars?
additional treatment choices at a lower cost
increased access to biologics, which may lead to improved health outcomes overall
Describe the difference in bringing a biosimilar to market compared to a generic drug.
bringing a biosimilar to market is more costly and less certain than producing a generic drug
-generic: 3yrs, $1-2 million, gain ~90% of market in 1yr
-biosimilar: 5.5-7.5yrs, $10-40 million, market share uncertain
Differentiate between generics and biosimilars based on the following criteria:
-molecular complexity/manufacturing
-immunogenicity
-approval
-same generic name
-indications
-interchangeability
-price discounts
molecular complexity/manufacturing:
-generics: simple products via chemical means, made same as brand name
-biosimilars: complex products by living cells, may vary in purification from brand
immunogenicity:
-generics: none
-biosimilars: yes
approval:
-generics: must show bioequivalence
-biosimilars: at least 1 clinical trial for toxicity, immunogenicity, PK, analytical studies
same generic name:
-generics: yes
-biosimilars: no, may have different
indications:
-generics: same as brand
-biosimilars: may or may not have same as brand
interchangeability:
-generics: yes
-biosimilars: not automatically
price discounts:
-generics: 50-90% of brand
-biosimilars: 25-50% of brand
Where does the difference lie in developmental pathways when comparing biologics to biosimilars?
biologics:
-focused on clinical studies
biosimilars: pyramid is inverted
-focused on analytical studies
Describe the approval process for biosimilars.
comparative evidence to the innovator must be provided to HC
totality of evidence:
-similarity based on entire submission, including data derived from comparative structural, functional, non-clinical and clinical studies
quality:
-chemistry and manufacturing; must use same aa sequence
non-clinical:
-pharmacology and toxicology
clinical:
-pharmacology, safety, efficacy
What does it mean to be highly similar?
minor differences between the reference product and the proposed biosimilar product in clinically inactive components are acceptable
Who decides if a biosimilar and innovator may be interchangeable?
the provinces
-authorization of a biosimilar is not declaration of interchangeability nor substitutability
What kind of monitoring occurs once a biosimilar has hit the market?
post-marketing safety programs (phase 4)
True or false: the dosage form, strength, and route of administration of the biosimilar should be the same as that of the reference biologic
true
What can be done with information about a biosimilar after it has hit the market?
information can be extrapolated to other indications where clinical studies not done
What are some key aspects that may be considered for extrapolation of a biosimilar for new indications?
MOA in each condition
PK and biodistribution
expected toxicities
any other factor
Differentiate between generics and biosimilars based on interchangeability and substitution.
generics:
-regulatory or payer agencies may designate the two as interchangeable
-pharmacists may be authorized/required to substitute a generic for the original without informing the physician
biosimilars:
-biosimilarity status by a regulator does not imply interchangeability
Which continent has the most amount of approved biosimilars?
Europe
-Canada has less than Europe and the US
What are some reasons for the low uptake of biosimilars?
lack of pharmacy awareness and not carrying them
lack of prescriber awareness
not first to market=not first to mind
patient and physician reluctancy to change
As of 2018, when a generic is available, they are used ___ of the time. When a biosimilar is available, they accounted for ___ of biologic spending.
90.3%
9.1%
Which province was the first to introduce the Biosimilars Initiative?
BC
What have the effects of the Biosimilar Initiative been in BC?
prompted private plans to copy the governments switching policy
in Dec 2021, private drug plan biosimilars share of the total eligible amount for biologics with biosimilar options was 65% in BC, compared to 12% in the rest of Canada
Are biosimilars safe and effective?
they undergo testing in clinical trials similar to innovators
some data relies on the innovator but it is a rigorous approval process
shows that the 2 medicines are highly similar
any difference between the 2 medicines should have no impact on safety or efficacy
Are biosimilars interchangeable?
no
What is the nocebo effect?
a patients negative expectations affect the treatment outcomes
How can we help combat the nocebo effect?
acknowledge it; empathy
speak face to face
be informed and provide information
promote a neutral or positive outlook
