Biologic Drugs

Question 1

What are biotech drugs?

Answer 1

A medication derived from a living organism or their cells

Larger and more complex than traditional pharmaceutical products

Question 2

How is the synthesis of biologics similar to small molecule pharmacueticals?

Answer 2

Biologics are is produced from genetically engineered living organisms or cells

Small molecule pharmaceuticals are formed through chemical synthesis

Question 3

Is the molecular structure of biologics fully known?

Answer 3

No, it is complex and frequently partiallly unknown

Question 4

What is the risk of contamination of biologics during manufacturing?

Answer 4

Higher compared to small molecule pharmaceuticals

Question 5

Are biologics more resistant to physical factors compared to small molcule pharmaceuticals?

Answer 5

No, biologics are less resistant to physical factors

Question 6

What are some relative ADME properties associated with biologics compared to small molecule pharmaceuticals?

Answer 6

Absorption (Slower)
Distribution (Low/Limited)
Metabolism (Catabolized to endogenous amino acids)
Excretion (target-mediated)

Question 7

What additional information do biologics manufacturers have to provide Health Canada for drug approval compared to small molecule pharmaceuticals when seeking approval?

Answer 7

Must include more detailed chemostry and manufacturing information (this done to confirm the purity and quality of the product)

Question 8

What are the six types of biologic products used in pharmacotherapy?

Answer 8

1. Blood and blood components
2. Proteins
3. Human Tissues
4. Vaccines
5. Allergenic Extracts
6. Cellular & Gene Therapies

Question 9

What are some commonly used biologics?

Answer 9

Insulin

Botox

Infliximab (Remicade)

Question 10

What is the place of monoclonal antibodies in COVID-19 treatment?

Answer 10

Used in early treatment in mild-moderate COVID-19 illness in at-risk patients

They will bind to healthy cells, preventing viral insertion into healthy cells

ex. Evusheild & Regeneron

Question 11

Is spending on biologic drugs decreasing over time?

Answer 11

No, the proportion and magnitude of drug spending on biologics is increasing.

ex. In 2020 ($278bil/year) vs. 2023 ($465bil/year)

Question 12

Do biologics make up more than 30% of new drug approvals by the FDA?

Answer 12

Yes, and the proportion increases every year

2022 (40.5% of drug approvals were for biologics)

Question 13

Are the most innovative drugs released in Canada at the same time as the United States?

Answer 13

No, only 1/3 of drugs new approved drugs (from 2016 to 2020) in the USA and Europe were approved in Canada

Question 14

What is the most common indication for biologics?

Answer 14

Neoplasms and Cancer therapies are the most common indication for biologic treatments

Question 15

What biologic product saw the greatest sales in 2022?

Answer 15

Comirnaty (BioNTech/Pfizer) was 1st, with over $40 billion in sales

COVID-19 vaccine

The Moderna vaccine was 2nd place

Question 16

Why are biologics so expensive?

Answer 16

1. Manfacturing costs
2. R&D costs
3. Competition (free market and benchmark pricing)
4. Many biologics target rare diseases, so the market for them is small (economies of scale)

Question 17

What is the function of intellectual property rights for drug manufacturers?

Answer 17

They provide market exclusivity (competing firms cannot use clinical trial data to formulate a generic version immediately)

This helps innovative firm to recuperate drug development costs and generate profit (incentivises drug manufactures to conduct difficult and expensive R&D, especially for biologics)

Question 18

What is a biosimilar?

Answer 18

A “copy” of a commercially availavle biopharmaceutical (reference product) that no longer has patent protection

This “copy” must satisfy the following requirements:
- Rigourous analytical and clinical assessment in comparison to reference product
- Approved by regulatory agency according to a biosimilar evaluation pathway

Question 19

Are biosimilars priced at significant discounts compared to their reference products?

Answer 19

Yes, but the discounts are not as significant (25-50% off compared to brand) compared to generic drugs (50-90% discount) for small molecule pharmaceutics

This is because the process of showing bioequivalence of a biosimilar to a reference product, costs a alot more compared to getting a generic drug approved

Question 20

What types of evidence needs to be given to Health Canada for approval of biosimilar?

Answer 20

Totality of evidence (final determination of similarity is based on the etire submission, including data derived from comparative structural, functional, non-clinical and clinical studies”

Quality: chemistry and maufacturing (must use the same amino acid sequence)

Non-clinical: pharmacology and toxicology

Clinical: pharmacology, safety, and efficacy

Question 21

Are biosimilars expected to be completely identical to the reference product?

Answer 21

No, minor differences between the reference product and the proposes biosimilar product in clincally inactive components are acceptable

Question 22

What are some parameters that should be the same between reference product and proposed biosimilar?

Answer 22

• Dosage form
• Strength
• Route of administration

Question 23

Is post-marketing required for biosimilars?

Answer 23

Yes, post-marketing is mandatory (looks for issues with biosimilar not caught in the clinical trials and approval process at large)

Question 24

What jurisdiction decides whether a given biosimilar is interchangeable with a reference product?

Answer 24

The provincial authorites pertaining to the regulation of pharmacy

Question 25

Does biosimilar status alone permit interchangeability?

Answer 25

No, a given biosimilar must be separately approved for interchangeability

Question 26

Are any adverse events expected when switching from a reference product to a biosimilar?

Answer 26

No differences are expected in efficacy and safety following a change in routine use between a biosimilar and its reference biologic drug in an authorized indication

Question 27

How many biosimilars have been approved in Canada?

Answer 27

As of Feb 2023, 53 authorized biosimilars for sale by Health Canada for 15 separate innovator products (some reference products have multiple biosimilars)

Question 28

What was the intake of biosimilars prior to the 2020s?

Answer 28

Very low, limited incentive to switch from reference product to biosimilar (lack of practitioner knowledge and small discounts)

Question 29

Are the cost savings from using biosimilars significant?

Answer 29

Yes, billions of dollars saved on drug costs could improve accessibility

Question 30

Is Canada ahead in the uptake of biosimilars compared to its peer nations?

Answer 30

No, it is behind countries in Europe and the USA. The uptake of biosimilars was lower in Canada vs the afforementioned nations

Question 31

What has been done to improve the uptake of biosimilars in Canada?

Answer 31

Biosimilar initiatives across Canadian provinces (including SK) have drastically increased ht proportion of patients using biosimilars

Public plans no longer pay for certain reference products, they will only pay for approved biosimilars

Biosimilar penetration has reached 65% in some jurisdictions in Canada (BC)

Question 32

What are some common questions patients ask pharmacists about biosimilars?

Answer 32

1. Is there a generic (not quite)
2. Are they safe (Yes, extensive testing and analysis)
3. Cost/reimbusement (lower cost and some provinicial plans refuse to pay for reference product)
4. Benefit risk:ratio (in most patients, benefits are more significant vs. risks)
5. Post-marketing surveillance
6. Differentiating between biosimilars
7. Counselling on these products

Question 33

What is the nocebo effect?

Answer 33

Like the placebo effect, if a patient has preconcieved negative attitudes for a biosimilar, it can impact treatment outcomes