L14 Generics

Question 1

Genetic Drugs must provide evidence of…

Answer 1

copies of innovator drugs, they provide evidence of:

1. safety: by demonstrating chemical comparability to innovator drug in the lab
2. efficacy: by demonstrating bioequivalence to innovator drug in a clinical trial (bioequivalence study)

Question 2

Generic drugs are cheaper because…

Answer 2

1. no preclinical studies required:
   - depend on comparability to innovator for animal studies to demonstrate safety
2. no extensive clinical trials required:
   - to prove comparability to the innovator, they need a single relatively small bioequivalence clinical study
   - depend on comparability to innovator to access multiple large scale clinical trials to prove safety and efficacy

Question 3

The basic generic strategy

Answer 3

see onenote diagram

loss of innovator IP => generic business => money (benefits for investors, economy, consumers)

• expiry/invalidation/circumvention of innovator IP is central to a generic business
• value of a company is determined by the value of its ability to gain earliest market entry for a pipeline of drugs

Question 4

Generic competition - a virtuous cycle

Answer 4

see onenote diagram

Question 5

Comparisons of strategies

Answer 5

see onenote

Question 6

Innovator drug loyalty

Answer 6

Even though IP patent expires, trademark, copyrights, registered designs still exist for that brand e.g. Design for Panadol packaging

• Allows innovator’s market to still exist
• Initial monopoly allows them to build brand loyalty and brand recognition

Question 7

What is a generic drug? - simple generic

Answer 7

• a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use

Question 8

Brand/reference drug

Answer 8

• usually innovator
• has full safety and efficacy information submitted to FDA, TGA etc.
• product registered and already marketed in country of interest

Question 9

Studies to demonstrate comparability with innovator product include

Answer 9

1. lab studies
   - chemical content and purity
   - dissolution studies for oral products
   - microbiological safety
   - stability
2. clinical bioequivalence
   - needed for most products including oral drugs
   - not needed for some products e.g. simple IV solutions

Question 10

Compared with innovator, the generic drug should have…

Answer 10

see onenote

1. same API
2. same route of admin
3. same dosage form
4. same strength
5. same conditions of use
6. same inactive ingredients approved
7. same drug profile i.e. is bioequivalent

if these conditions are fulfilled, generic is interchangeable with innovator in clinical use

Question 11

Development of a generic drug

Answer 11

see onenote diagram

Question 12

Generic vs Innovator route comparison

Answer 12

see onenote table

Question 13

Bioequivalence

Answer 13

see diagram and side notes

• look at drug concentration in blood

Question 14

Genetic drugs - comment on quality

Answer 14

see onenote

“variation between different batches of an originator product is often of the same magnitude or even greater than the statistically calculated and controlled difference between a generic and its reference product”

BUT changes in appearance can result in patients discontinuing medication and hence is of concern

Question 15

Complex generic drugs

Answer 15

see onenote

1. incomplete physico-chemical comparability
2. different admin route
3. difference usage
4. improved bioavailability or site and duration of action (“supergeneric”)
5. requires more data than simple generics to support safety and efficacy of drug
6. increased, separate regulatory requirements
7. may not be clinically interchangeable with innovator drug

Question 16

Pregabalin

Answer 16

see onenote

- simple defined molecule

Question 17

Erythropoietin

Answer 17

see onenote

- complex glycan structures of individual molecules

Question 18

Example of biosimilar - Erythropoietin

Answer 18

Eprex vs Retacrit

• both has extensive physico-chemical lab testing
• both have extensive animal studies
• both have large clinical trials involved but…Eprex had over 6000 patients involved, Retacrit only around 1600 patients

Question 19

Biosimilars - US EU comparison

Answer 19

see onenote table

• no clear definition, only that it is comparable in quality, safety and efficacy to a reference product

Question 20

Biosimilars - recent progress

Answer 20

see onenote

Question 21

Biosimilars vs simple generic drugs

Answer 21

see onenote

• biosimilar are comparable to, not necessarily substitutable for innvaotr
• generics are equivalent to, and substitutable for innovator
• biosimilars - more extensive physico-chemical comparability evidence than generics, PD/PK studies

Question 22

Biosimilars - interchangability

Answer 22

see onenote

• interchangability is required to allow substitution of a brand biological medicine with a biosimilar by a pharmacist

Question 23

Simple generics vs Complex generics vs Biosimilars

Answer 23

see onenote

Simple generics = exact copies of small molecular weight drugs
- clinically interchangeable

Complex generics = copies of small molecular weight drugs with minor modifications
- may not be clinically interchangeable

Biosimilar = copies of large molecular weight drugs (biopharmaceuticals)
- not in general clinically interchangeable

Question 24

Biopharmaceutical

Answer 24

a biological macromolecule or cellular component, such as a blood product, used as a pharmaceutical.