Biologics/Biosimilars Flashcards
What are biotech drugs?
A medication derived from a living organism or their cells
What size are biologics?
Large and complex
What is the manufacturing process of biologics?
Host cell development
Master cell bank establishment
Protein production
Protein Purification
Analysis
Formulation
Storage and handling
How do biologics differ from small molecule pharmaceutics based on synthesis?
small molecules are chemically synthesized whereas biologics are genetically engineered from living organisms/cells
How do biologics differ from small molecule pharmaceutics based on size?
Biologics are large wherease traditional pharmaceutics are small
How do biologics differ from small molecule pharmaceutics based on structure?
Biologics are complex, and frequently partially unknown whereas small molecules are usually fully known
Biologics complex, spatial structures and difficult to determine and small molecules vice versa
How do biologics differ from small molecule pharmaceutics based on susceptibility to contamine during manufacturing?
Low in small molecules, high in biologics
How do biologics differ from small molecule pharmaceutics based on sensitivity to physical factors?
low and higher respectively
How do biologics differ from small molecule pharmaceutics based on clinical behaviour?
Well understood mode of action vs complicated mode of action/not well understood
How do biologics differ from small molecule pharmaceutics based on species?
interdependant vs specific
How do biologics differ from small molecule pharmaceutics based on immunogenicity
non antigenic vs antigenic
How do biologics differ from small molecule pharmaceutics based on ADME?
Faster, high, metabolized to non-active, rarely target mediated vs slower, low/limited, catabolized to endogenous amino acids, often target-mediated
How do biologics differ from small molecule pharmaceutics based on PK profile?
linear vs non-linear
How do biologics differ from small molecule pharmaceutics based on haf-life
short(er) vs long
How do biologics differ from small molecule pharmaceutics based on saftey?
toxcicity vs exaggerated pharmacology
How are biologics regulated in Canada?
Health Canada mximize saftey and efficacy,
trials,
must include more detailed chemistry and manufacturing information compared to other drugs to ensure purity and quality of product,
In NDS must have product specific facility info,
Inspection of manufacturing facility (On-site evaluation OSE) must be done to assess production process and facility
IF NDS good then given a Notice of compliance (NOC) and a DIN to then be approved to be sold in Canada
Monitored by using a lot release schedule
products are heavily scrutinized before proceeding to release process
Health Canada and Public agency of Canada monitor biologics for and adverse events, complaints, problems.
How has the overally spending of biologics changed in Canada?
Trending up; 6.4% increase in last 4 years but, predicted to go from 278b/yr to 465b/yr (2020-2023 globally)
What are some of the major Biotech company’s?
Pfizer
J & J
Roche
Merck & Co
AbbVie
Novartis
Bristol Myers Squibb
Sanofi
AstraZeneca
GlaxoSmithKline
Explain the research and development process of biologics (PHAR 122)
Basic research –> drug discovery –> pre-clinical –> phase I –>phase II –> phase III –> FDA review –> FDA approved –> Post-approval research and monitoring (phase IV)
What is the major biotech product by indication?
Top 3:
Neoplasms/cancer/oncology
Infectious and parasitic disease
Nervous system diseases
What products were the leading pharmaceutical biotech company’s by sale world wide?
Comirnaty (BioNTech/Pfizer)
Spikevax (moderna)
Humira (AbbVie)
What are biotech stocks like?
Very volatile
What is still the market leader for biotech?
Oncology; Keytruda may hit 26b/yr by 2025
Why are biologics so expensive?
manufacturing costs
R&D costs
competition
small market of use (most biologics target rare diseases)
What are Intellectual property rights?
Provide Market exclusivity
A period of time following marketing approval when competing firms may not use the clinical trail data of parent company in order to obtain marketing authorization for a generic version (essentially like patton)
Data exclusivity grants inoovator a period of protection for their investment in clinical trials and data collection regardless of the length of time it takes to bring drug to market
What are some future issues a biotech company may run into?
Market exclusivity stops, competing products enter market
REvenue threatened by increased scrutiny from government health agencies
What is a biosimilar?
A highly similar product to an innovator product; very similar physiochemical characteristics, efficacy, and saftey.
Is Health Canada’s approval of a biosimilar a stamp of bioequivalance?
No,
WHat are some parameters of biosimilar approval?
undergone rigorous analytical and clinical assessment in comparison to refernce product
Been approved by regulatory agency according to a specific pathway for biosimilar evaluation
Is creating a biosimialr as effective as a generic drug development?
No, market shar uncertain, more costly and time consuming than a generic drug creation.
Compare Biosimilars vs Generics in molecular complexity/manufacturing
Generics: simple, made exact same way as brand name
Biosimilar: Complex, may vary in purification from brand
Compare Biosimilars vs Generics in immunogenecity
Generic: None
Biosimilar: Yes
Compare Biosimilars vs Generics in Approval
Generic: must show bioequivalence
Biosimialr: conduct atleast 1 clinical trial for toxicity, immunogenecity, PK, analytical studies
Compare Biosimilars vs Generics in same generic name
Generics: yes
Biosimialrs: No, may be different
Compare Biosimilars vs Generics in indications
Generic: same as brand
biosimialr: may not have same as brand
Compare Biosimilars vs Generics in interchangeability
Generic: yes
biosimilar: not automatically
Compare Biosimilars vs Generics in price dicount
Generic: 50-90% of brand
Biosimilar: 25-50% of brand
How do biosimlar developmental pathways differ from standard biologics?
Essentially flip-flopped;
Comparitive clinical studies –>comaprative clincial PK/PD –> nonclinical –> analytical
whereas biolgic is flipped
What is the approval process of Biosimilars?
Comparitive evidence to innovator provided to Health Canada
Totality of evidence; final determination of similarity based on entire submission including data derived from comparative structural, functional, non-clinical, and clincal studies
Quality: chemistry and manufacturing must use the same AA sequence
Non-clinical: pharmacology and Toxicity
Clinical: Pharmacology, safety, efficacy
What is meant by highly similar?
minor differences between the reference product and the proposed biosimilar product in clinically INACTIVE components are acceptable
Is authorization of a biosimilar a declaration of interchangeability?
NO
What is the most common type of biologic?
Monoclonal Antibodies
Many biologics enter research. How many make it through?
1
Who decides if a biosimilar can be interchangeable with its innovator product?
Provinces decide (I.E Sask decides for us)
What condition is biologics used most for?
Cancer
How can biosimilars approved for other indications?
Extrapolation from othe data, new clinical studies do not need to be preformed
What is required for extrapolation of biosimilar data for new indications?
Scientific justification;
MOA in each condition
Expected toxicicty
PK and biodistribution
other factors such as comorbitities
What is the comparison if a generic being used vs a biosimilar being used (interchangeing w/ innovator)
Generic used 90.3% of time
Biosimilar: account for 9.1% of biologics spending
Who decides if the biosimilar is interchangeable?
provinces
For a new indication for a biosimilar do you need a new clinical study revolving around it?
No-can extrapolate
In order to extrapolate data from other studies of reference what is considered?
MOA, toxicity, PK,PD
In relation to cost, how has uptake of biosimilars been implemented?
HIgh unrealized savings= not always used
How are biosimilars differently utilized in Europe?
competition is more fierce, as biosimilars get 50% penetration of market share in 1 year for newer molecules
What is the biosimilar initiative?
in BC
mandatory switching of infliximab, glargine in 6 months
to include more
Pharmacist gets money if they aid in switching
What effect has the biosimilar initiative had?
private plans are copying the reimbursment of only biosimilars
use of biosimilars has skyrocketed
What has Sask done to improve biosimilar use?
copied BC
new patients starting biologics will only get coverage for biosimilars
What is nocebo effect?
negative expectations with non brand name
If patient refuses to switch with no words of reason to convince them (cost, work the same) what do you do?
respect decision and give them it but they may have to POP
