Generics:

Conceptions and
Misconceptions
Anand Srinivasan
Department of PHARMACOLOGY, AIIMS-BBSR

Types of drugs based on the

Originality
Original or Innovator product
Cost of development is very high

Generic
Cost of development is negligible compared against the
original product

Regulatory agencies
India
CDSCO
DCGI Head of CDSCO

USA
FDA

Innovator Molecule
Development time 5 years on average
Cost of development 2.5 billion USD
Number of participants In thousands

Drug Development Process Original

IND
IND
applicati
applicati
on
on

NDA
NDA
applicati
applicati
on
on

Drug Development Process Original

Patent period after filing IND 20 years

Generics - Dictionary
Not protected by trademark registration
Non-proprietary or any product, as a food, drug,
or cosmetic that can be sold without a brand
name

Generics - WHO
A generic drug is a pharmaceutical product,
usually intended to be interchangeable with an
innovator product that is manufactured without
a license from the innovator company and
marketed after the expiry date of the patent or
other exclusive rights

Bioequivalence - FDA
A generic drug is bioequivalent (BE) if
The rate and extent of absorption of the
drug do not show a significant difference
from the rate and extent of absorption of
the listed drug when administered at the
same molar dose of the therapeutic
ingredient under similar experimental
conditions in either a single dose or
multiple doses

Generics - Development

Preclinical
studies

Bioequivalent
studies

ANDA Abbreviated New Drug Application

Generics
Period of development Months
Cost of development Very less
Number of participants 100s

Generics - Development
Preclinical BE studies
Dispersion
Chemical Analysis

Principles of BE studies
Cross over trial
To accommodate intra-individual variability

Randomised to
O THEN G or
G THEN O

Principles of BE studies
Parameters measured
Cmax, Tmax, AUC

BE studies Statistical
considerations
Equivalence studies
90% confidence interval
Ratio of geometric means
Acceptance criteria: 80 125%
Log transformed AUCT & Cmax

Nomenclature of drugs
Chemical name
5-({4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}methyl)1,3-thiazolidine-2,4-dione

Drug name
Pioglitazone

Brand name
Actos

Branded Generics
Not a recognized term legally
Practiced in India and a few other countries
Not used in USA or Europe
Braded generics - Pioz

Branded Vs Generic
Quality
The 2014 episode of death of 13 women and
illness of 138 following tubectomy and
prescription of poor quality ciprofloxacin

Branded Vs Generic
Cost
Generic is cheaper

Branded Vs Generic
Efficacy and Safety
Comparing Tolerability and Efficacy of Generic
versusBrand Alendronate: A Randomized Clinical
Study inPostmenopausal Women with a Recent
Fracture
PLoS ONE 8(10): e78153.
doi:10.1371/journal.pone.0078153

Problems in India
Almost all are generics
Variable cost of branded generics
??Shift of health care from doctors to pharmacists

Problems in India
Understaffed CDSCO and regional labs

Private study

Problems in India
Recognition of product patent

Biosimilars
Generic equivalent of biologicals
Drugs are almost similar and not exactly similar
Additional studies needed
Additional regulatory authorities involved
DBT - Review Committee on Genetic Manipulation
Ministry of Environment

Biosimilars - Development
Preclinical
Studies

Structur
e
Toxicity

Kinetics

Dynamics

Suggestions
Prescription of generic drugs who have displayed
the data publicly and from companies who
export to western nations
Avoid unnecessary switching of brands
Avoid brand switching for narrow therapeutic
drugs
Avoid switching brands for biologicals and
biosimilars

References
FDA
CDSCO
Only generics (drugs/names): Is India ready?
Dhamija P et al. Indian Journal of Endocrinology and
Metabolism / Sep-Oct 2015 / Vol 19 | Issue 5

Substandard drugs
Johnston et al. Br J Clin Pharmacol / 78:2 / 218243