RAC- chapter 3 Questions and Answers
Decision Tree - Answer-1.Drug,Device or Some Combination - For human use -drug -
new drug = New NDA Route 505(b)(1)
2.Drug,Device or Some Combination- For human use -drug- NOT new drug- same
formulation as RLD=ANDA Route
3. Drug,Device or Some Combination- For human use -drug- not new drug- NOT same
formulation as RLD- Right of reference to original NDA=NDA Supplement ( same
formulation, new indication, new route)
4. Drug,Device or Some Combination- For human use -drug- not new drug- NOT same
formulation as RLD- NO Right of reference to original NDA= NDA Route 505(b)(2)
( indication expansion approaches and bridging strategies)
5. Drug,Device or Some Combination- For human use -drug- not new drug- NOT same
formulation as RLD- Permutation of RLD formulation ,but same label being pursued=
Submit Suitability Petition - if Accepted ANDA Route ; if Not accepted NDA Route
505(b)(2)
6.Drug,Device or Some Combination- For human use -drug- not new drug- Same
formulation as RLD-ANDA Route
7. Drug,Device or Some Combination - Not For human use - New Animal Drug
Application (NADA)
SPA Draft Guidance for Industry : Special Protocol Assessment - PUDUFA II - Answer-
FDA needs to evaluate certain protocols and related issues within 45 days of receipt , 3
types of protocols eligible for an SPA
1) animal carcinogenicity protocols 2) finial products stability protocols 3) human clinical
trial protocols when the data will form the basis for an efficacy claim for example for
phase 3 or pivotal trial to be discussed at an End-of- Phase 2/ Pre-Phase 3 meeting)
NDA 505(b)(1) -definition - Answer-Drug is defined as a product used in diagnosing,
curing, mitigating, treating or preventing a disease or affecting a structure or function of
the body - from 21 CFR 310.3
New drug is : a new use of a drug substance or component such as active ingredient,
excipient, carrier, coating etc; or a new use of combination of approved drugs ; change
in proportion of ingredients in a combination drug. new intended use for the drug,
change in dosage, method or duration of administration or application
NDA 505(b)(1)- scope - Answer-a drug containing a novel chemical compound as its
active ingredient ;
a drug containing an existing active ingredient approved for use as a medicine in the US
;
a drug previously approved by FDA but now proposed for a new use or indication;
a drug previously approved by FDA but in a different dosage form, route of
administration or other key condition of use than that approved originally
surrogate endpoint - Answer-"a biomarker intended to substitute for a clinical endpoint".
, a surrogate endpoint (or marker) is a measure of effect of a specific treatment that may
correlate with a real clinical endpoint but does not necessarily have a guaranteed
relationship.
New Chemical Entities( NCEs) and the NDA 505(b)(1) - key questions in DDP - Answer-
Safety - what is known safety profile of other similar drugs and the class of drugs ;
toxicity for target organs/systems ; toxicity in acute vs chronic condition; can toxicities
be monitored; are toxicities reversible; MTD and risk of overdose; safety findings and
adverse events
PK pharmacokinetics - compared to competitor products, time course of the effect
related to the time-concentration curve ;potential or actual interactions with other drugs;
is PK profile linear; drug concentrations intra-and inter-subject.
pharmacodynamics/efficacy/Benefit - endpoints;potential breadth of target indication;
target organs/systems; how to measure the benefits; time course and duration; what
happen to effects if stop dosing;minimal effective dose and duration; endpoint
measures.
New Chemical Entities( NCEs) and the NDA 505(b)(1)- PHS Act- Biologics and
Biologics License Application (BLA) - Answer-1. definition- Biologics are medical
products made from natural sources( human, animal or microorganism),such as
vaccines,blood and blood products for transfusion and or manufacturing into other
products, allergenic extracts,huaman cells and tissues used for transplantation, gene
therapies, cellular therapies, tests to screen potential blood donors for infectious agents
such as HIV
2. BLA regulations in 21 CFR 601.2 similar in content to NDA, within the charge of
CBER who focus on therapeutic proteins , but more complex biological products such
as gene therapy, monoclonal antibodies, peptides and well-characterized proteins lie on
CDER after 2003.
New Chemical Entities( NCEs) and the NDA 505(b)(1)- Generic Biologics and
Biosimilars - Answer-Biologics Price Competition and Innovation Act(BPCI Act)
Biosimilar products are allowed to have only minor differences in clinically inactive
components and must hot have any clinically meaningful differences in terms of safety
and effectiveness from the reference product.
Interchangeable biological product must meet additional standards to allow a
pharmacist to substitute the new biological for the reference product.
New Chemical Entities( NCEs) and the NDA 505(b)(1)- User Fee -Biosimilar
Investigational New Drug application - Answer-FDA can collect user fee for biosimilar
biological products during IND phase
New Chemical Entities( NCEs) and the NDA 505(b)(1)- Orphan Drug Designation -
Answer-1983 Orphan Drug Act several times amendment: 1. 1984 redefined 'rare
disease or condition' as affecting fewer than 200,000 persons in the US'.2. 1985
extended the marketing exclusivity to all drugs and allowed federal grants for the clinical
evaluation 3. 1988 required industry sponsors to apply for orphan designation prior to
Decision Tree - Answer-1.Drug,Device or Some Combination - For human use -drug -
new drug = New NDA Route 505(b)(1)
2.Drug,Device or Some Combination- For human use -drug- NOT new drug- same
formulation as RLD=ANDA Route
3. Drug,Device or Some Combination- For human use -drug- not new drug- NOT same
formulation as RLD- Right of reference to original NDA=NDA Supplement ( same
formulation, new indication, new route)
4. Drug,Device or Some Combination- For human use -drug- not new drug- NOT same
formulation as RLD- NO Right of reference to original NDA= NDA Route 505(b)(2)
( indication expansion approaches and bridging strategies)
5. Drug,Device or Some Combination- For human use -drug- not new drug- NOT same
formulation as RLD- Permutation of RLD formulation ,but same label being pursued=
Submit Suitability Petition - if Accepted ANDA Route ; if Not accepted NDA Route
505(b)(2)
6.Drug,Device or Some Combination- For human use -drug- not new drug- Same
formulation as RLD-ANDA Route
7. Drug,Device or Some Combination - Not For human use - New Animal Drug
Application (NADA)
SPA Draft Guidance for Industry : Special Protocol Assessment - PUDUFA II - Answer-
FDA needs to evaluate certain protocols and related issues within 45 days of receipt , 3
types of protocols eligible for an SPA
1) animal carcinogenicity protocols 2) finial products stability protocols 3) human clinical
trial protocols when the data will form the basis for an efficacy claim for example for
phase 3 or pivotal trial to be discussed at an End-of- Phase 2/ Pre-Phase 3 meeting)
NDA 505(b)(1) -definition - Answer-Drug is defined as a product used in diagnosing,
curing, mitigating, treating or preventing a disease or affecting a structure or function of
the body - from 21 CFR 310.3
New drug is : a new use of a drug substance or component such as active ingredient,
excipient, carrier, coating etc; or a new use of combination of approved drugs ; change
in proportion of ingredients in a combination drug. new intended use for the drug,
change in dosage, method or duration of administration or application
NDA 505(b)(1)- scope - Answer-a drug containing a novel chemical compound as its
active ingredient ;
a drug containing an existing active ingredient approved for use as a medicine in the US
;
a drug previously approved by FDA but now proposed for a new use or indication;
a drug previously approved by FDA but in a different dosage form, route of
administration or other key condition of use than that approved originally
surrogate endpoint - Answer-"a biomarker intended to substitute for a clinical endpoint".
, a surrogate endpoint (or marker) is a measure of effect of a specific treatment that may
correlate with a real clinical endpoint but does not necessarily have a guaranteed
relationship.
New Chemical Entities( NCEs) and the NDA 505(b)(1) - key questions in DDP - Answer-
Safety - what is known safety profile of other similar drugs and the class of drugs ;
toxicity for target organs/systems ; toxicity in acute vs chronic condition; can toxicities
be monitored; are toxicities reversible; MTD and risk of overdose; safety findings and
adverse events
PK pharmacokinetics - compared to competitor products, time course of the effect
related to the time-concentration curve ;potential or actual interactions with other drugs;
is PK profile linear; drug concentrations intra-and inter-subject.
pharmacodynamics/efficacy/Benefit - endpoints;potential breadth of target indication;
target organs/systems; how to measure the benefits; time course and duration; what
happen to effects if stop dosing;minimal effective dose and duration; endpoint
measures.
New Chemical Entities( NCEs) and the NDA 505(b)(1)- PHS Act- Biologics and
Biologics License Application (BLA) - Answer-1. definition- Biologics are medical
products made from natural sources( human, animal or microorganism),such as
vaccines,blood and blood products for transfusion and or manufacturing into other
products, allergenic extracts,huaman cells and tissues used for transplantation, gene
therapies, cellular therapies, tests to screen potential blood donors for infectious agents
such as HIV
2. BLA regulations in 21 CFR 601.2 similar in content to NDA, within the charge of
CBER who focus on therapeutic proteins , but more complex biological products such
as gene therapy, monoclonal antibodies, peptides and well-characterized proteins lie on
CDER after 2003.
New Chemical Entities( NCEs) and the NDA 505(b)(1)- Generic Biologics and
Biosimilars - Answer-Biologics Price Competition and Innovation Act(BPCI Act)
Biosimilar products are allowed to have only minor differences in clinically inactive
components and must hot have any clinically meaningful differences in terms of safety
and effectiveness from the reference product.
Interchangeable biological product must meet additional standards to allow a
pharmacist to substitute the new biological for the reference product.
New Chemical Entities( NCEs) and the NDA 505(b)(1)- User Fee -Biosimilar
Investigational New Drug application - Answer-FDA can collect user fee for biosimilar
biological products during IND phase
New Chemical Entities( NCEs) and the NDA 505(b)(1)- Orphan Drug Designation -
Answer-1983 Orphan Drug Act several times amendment: 1. 1984 redefined 'rare
disease or condition' as affecting fewer than 200,000 persons in the US'.2. 1985
extended the marketing exclusivity to all drugs and allowed federal grants for the clinical
evaluation 3. 1988 required industry sponsors to apply for orphan designation prior to
