Regulatory Class - Sept 26 Flashcards
Focus of FDA review of NDAs
Safe and effective, when used as labeled
Manufacturing consistency - preserve identity, strength, quality, and purity
Must contain substantial evidence from adequate and well-controlled investigations
“Adequate and well-controlled” Studies
Clear statement of objectives
Summary of methods of analysis
Study design that permits valid comparison with control
Selection assures subjects have disease/condition
Methods of assignment to minimize bias
Using only foreign clinical data
Population must be applicable to US
Done by qualified clinical investigators
FDA is able to validate data
Proprietary name
Name used to market the product
Includes: Primary and secondary choices, pronunciation, where it was derived, and pharmacological meaning
Reviewed to minimize risk, and prevent overstate of efficacy or superiority claims
Reviewed as early as end of Phase II; Reviewed 90 days prior to action date (FDA gets 180 days if submitted with IND)
Establishment registration
Information used to prepare inspections
Includes listing of all drugs in commercial distribution (if company already produces drugs, just add it to the listing)
Must be done prior to the production of final drug product
Labeler code assignment
National drug code (11-digit) provided to US drugs
First 4-5 digits are assigned by FDA - identify the labeler
Remaining digits assigned by manufacturer - identify product codes
Pre-NDA meeting
Type B meeting
4-6 months prior to anticipated submission date
Submit request 60 days prior to desired meeting date
Briefing package at least 4 weeks prior to meeting
Present clinical data to be submitted
Discuss format submission
NDA Patent Information
Submit information to verify that the sponsor has all the rights necessary to legally manufacture and sell the drug
Includes drug substance, drug product, and method-of-use
Debarment certification
Sponsor did not use services of anyone debarred by FDA
Debarred investigators may not receive investigational product
NDA Index
First document that should be made in creating the NDA
Use as an outline for the final submission
FDA Form 3454
Financial Certification
FDA Form 3455
Financial Disclosure
Labeling contents
Container / carton labels
Proposed package insert, includes an annotated version (links to special info in the submission) and a final ‘clean’ draft version
Package insert includes highlights of prescribing info:
Product names Boxed warning Recent major changes Indication and usage Dosage and administration Dosage forms and strengths Contraindications Warnings and precautions Adverse reactions Drug Interactions Use in specific population
Package insert - full prescribing info:
Includes all topics in the highlights and: Drug abuse and dependence Overdosage Clinical pharmacology Nonclinical toxicology Clinical studies References How supplied/ storage and handling Patient counseling info
Boxed Warnings
put on products that have a special risk
mainly used to inform physicians
NDA: Clinical Data: Other studies and information section
Any clinical info relevant to safety and effectiveness
List of countries where drug is approved
List of countries where drug has been disapproved or withdrawn from marketing
Integrated summary of effectiveness
included for each indication
Supports dosage and dose interval recommended in product labeling
Compare and analyze all results from controlled trials; address drug-demographic, drug-drug, and drug-disease interactions; describe any evidence of longterm effectiveness, tolerance, and withdrawal effects
Integrated summary of safety
safety data from all sources - including animal data, clinical studies, and foreign marketing experience
Adverse events from all studies
Analysis of clinical lab data, evaluating abnormalities; discussion of drug-drug interactions
Safety update reports
New safety data that could affect labeling, contraindications, warnings, precautions, AEs
Submitted 4 months after the initial submission if requested by the FDA
Pediatric use information
Requires: Safety and efficacy info; for proposed indications for use; all relevant pediatric populations, dosing and administration info
May be deferred if drug ready for approval before completing pediatric studies or they are delayed until additional safety or effectiveness data are collected
Pediatric use Exceptions for requirement
No meaningful therapeutic benefit over existing treatments
Not likely to be used in a substantial number of pediatric patients
Necessary studies are impossible or highly impractical
Evidence suggests drug would be ineffective or unsafe in all pediatric age groups
Orphan drugs
Or is reasonable attempts to produce a pediatric formulation have failed
NDA: Case report form tabulations
Must be provided for each patients from all Phase 2 and Phase 3 studies; For each patient from all Phase 1 pharmacology studies, Safety data from all clinical studies
NDA: Case report forms (CRFs)
For each patient that died
For any patients that withdrew due to an AE
