Discuss –
Orphan drug designation
Fast-track procedures,
Accelerated approval,
Emergency use authorization
Breakthrough Therapy
Priority review
Bioavailability, bioequivalence, therapeutic equivalence, and their clinical significance
Regulatory requirements of bioequivalence studies.
Precision medicine
Structure-Activity Relationships
principles of drug use in pregnancy
Pharmacovigilance, different methods of Causality assessment
,Q. Discuss the significance of fast-track procedures, accelerated approval, and
emergency use authorization. Dec 2023
Q. Discuss the significance of Breakthrough Therapy, and Emergency Use
Authorization. MOCK 2024
Orphan designation
The ODA comprised a bundle of push and pull policies to increase the number of
drugs developed for rare diseases.
Push policies offer
tax credit (25% of clinical R&D costs),
research grants for orphan R&D projects, and
no NDA/BLA submission fee (which may amount to over $3 million),
while a prolonged market exclusivity of 7 years pulls drug developments toward
indications with a low prevalence.
The ODA also bridges the period between IND and NDA approval by instituting that
orphan drugs are eligible for closer collaboration with the FDA and permitting
disease-tailored clinical trial designs. The FDA even encourages the use of
“innovative clinical trial methods such as adaptive and seamless trial designs,
modelling and simulations, and basket and umbrella trials.
, FAST-TRACK
In light of this emerging threat, the US, therefore, introduced the fast-track program in
1988 to “facilitate the development, and expedite the review of drugs to treat serious
conditions and fill an unmet medical need”.
Under this definition, serious conditions include AIDS, dementia, cancer, and heart
failure, but also epilepsy, depression, and diabetes.
In this context, the FDA interprets drugs treating a disease without other alternative
treatments to fill an unmet medical need. In the case of available treatment
alternatives, the unmet medical need could be filled with a new drug that is better
than the existing therapy.
Under the new fast track process, the pharmaceutical company meets and closely
collaborates with the FDA after a successful phase 1 trial to design a phase 2 trial
which can build the basis for approval.
If successful, this phase 2, instead of phase 3, trial would, therefore, be sufficient to
prove a drug’s safety and efficacy.
Under this program, the FDA can continually review evidence generated from clinical
trials (rolling review).
program also permits the FDA to demand a post-marketing trial in case of uncertain
side effects, toxicity, or treatment outcomes.
Accelerated approval
Similar to the fast-track program, accelerated approval can be obtained for drugs
treating a serious condition and hence fill an unmet clinical need.
Accelerated approval enables the FDA to judge a drug’s efficacy based on surrogate
rather than clinical endpoints.
Measuring a drug’s effect on patient survival may require a long trial duration and
follow-up with many enrolled patients, especially for cancer types with high 5- and
10-year survival rates, e.g., prostate or breast cancer. In contrast, surrogate
endpoints, such as tumor shrinkage or progression, can be more quickly observed
and occur in most patients. Therefore, the accelerated approval program expedited
drug development by shortening clinical trial durations and enabling trial designs with
fewer enrolled patients to measure surrogate endpoints.
Similar to drugs approved under the fast-track program, the FDA may require post-
marketing trials for drugs approved under the accelerated approval program
However, shorter and smaller trials pose a challenge to correctly evaluate a
drug’s risks and benefits. Drugs with fast-track or accelerated approval are
associated with more unrecognized adverse events and post-marketing safety
revisions, e.g., withdrawals or warnings.
Orphan drug designation
Fast-track procedures,
Accelerated approval,
Emergency use authorization
Breakthrough Therapy
Priority review
Bioavailability, bioequivalence, therapeutic equivalence, and their clinical significance
Regulatory requirements of bioequivalence studies.
Precision medicine
Structure-Activity Relationships
principles of drug use in pregnancy
Pharmacovigilance, different methods of Causality assessment
,Q. Discuss the significance of fast-track procedures, accelerated approval, and
emergency use authorization. Dec 2023
Q. Discuss the significance of Breakthrough Therapy, and Emergency Use
Authorization. MOCK 2024
Orphan designation
The ODA comprised a bundle of push and pull policies to increase the number of
drugs developed for rare diseases.
Push policies offer
tax credit (25% of clinical R&D costs),
research grants for orphan R&D projects, and
no NDA/BLA submission fee (which may amount to over $3 million),
while a prolonged market exclusivity of 7 years pulls drug developments toward
indications with a low prevalence.
The ODA also bridges the period between IND and NDA approval by instituting that
orphan drugs are eligible for closer collaboration with the FDA and permitting
disease-tailored clinical trial designs. The FDA even encourages the use of
“innovative clinical trial methods such as adaptive and seamless trial designs,
modelling and simulations, and basket and umbrella trials.
, FAST-TRACK
In light of this emerging threat, the US, therefore, introduced the fast-track program in
1988 to “facilitate the development, and expedite the review of drugs to treat serious
conditions and fill an unmet medical need”.
Under this definition, serious conditions include AIDS, dementia, cancer, and heart
failure, but also epilepsy, depression, and diabetes.
In this context, the FDA interprets drugs treating a disease without other alternative
treatments to fill an unmet medical need. In the case of available treatment
alternatives, the unmet medical need could be filled with a new drug that is better
than the existing therapy.
Under the new fast track process, the pharmaceutical company meets and closely
collaborates with the FDA after a successful phase 1 trial to design a phase 2 trial
which can build the basis for approval.
If successful, this phase 2, instead of phase 3, trial would, therefore, be sufficient to
prove a drug’s safety and efficacy.
Under this program, the FDA can continually review evidence generated from clinical
trials (rolling review).
program also permits the FDA to demand a post-marketing trial in case of uncertain
side effects, toxicity, or treatment outcomes.
Accelerated approval
Similar to the fast-track program, accelerated approval can be obtained for drugs
treating a serious condition and hence fill an unmet clinical need.
Accelerated approval enables the FDA to judge a drug’s efficacy based on surrogate
rather than clinical endpoints.
Measuring a drug’s effect on patient survival may require a long trial duration and
follow-up with many enrolled patients, especially for cancer types with high 5- and
10-year survival rates, e.g., prostate or breast cancer. In contrast, surrogate
endpoints, such as tumor shrinkage or progression, can be more quickly observed
and occur in most patients. Therefore, the accelerated approval program expedited
drug development by shortening clinical trial durations and enabling trial designs with
fewer enrolled patients to measure surrogate endpoints.
Similar to drugs approved under the fast-track program, the FDA may require post-
marketing trials for drugs approved under the accelerated approval program
However, shorter and smaller trials pose a challenge to correctly evaluate a
drug’s risks and benefits. Drugs with fast-track or accelerated approval are
associated with more unrecognized adverse events and post-marketing safety
revisions, e.g., withdrawals or warnings.
