Overview of RA
Investigational New Drug (IND)
application
• An Investigational New Drug (IND) application is submitted to the FDA
to request permission to begin human clinical trials for a new drug. The
application includes detailed information to ensure the drug is safe for
human testing.
Preclinical Data (Animal and Laboratory
Studies)
Pharmacology and Toxicology Studies:
Data on the pharmacokinetics of drug
Toxicity and safety studies in animals
Study Reports: Summaries of all preclinical study findings
Chemistry, Manufacturing, and Controls
(CMC) Data
Drug Substance Information:
Chemical structure and properties
Manufacturing process
Stability studies
Drug Product Information:
Formulation details (e.g., tablet, injection, etc.)
Packaging and labeling
Quality control tests and specifications
Clinical Trial Protocol and Investigator
Information
•Clinical Protocol (for Phase 1 studies)
•Study design, objectives, inclusion/exclusion criteria
•Dosing plan and safety monitoring procedures
•Data collection and statistical analysis plan
•Investigator’s Brochure (IB)
•Summary of available data
Clinical Trial Protocol and Investigator
Information
Investigator Information:
•Experience and qualifications of the principal investigator
•Facilities where the study will be conducted
New Drug Application (NDA)
• A New Drug Application (NDA) is submitted to the FDA to request
approval for marketing a new drug in the U.S. It includes extensive data
demonstrating the drug's safety, efficacy, and manufacturing quality.
Administrative & Product Information
Application form for NDA submission
Proposed Drug Labeling – Package insert, prescribing information, and
patient information
Patent and Exclusivity Information – Details on patent protection and market
exclusivity claims
Summary Section
Overall Summary – Brief overview of the drug's safety, efficacy, and
benefits
Technical Summary – High-level summary of pharmacology, clinical, and
CMC data
Chemistry, Manufacturing, and Controls
(CMC) Data
Drug Substance (Active Ingredient):
Chemical structure, properties, and synthesis process
Analytical methods and stability data
Drug Product (Final Formulation):
Composition, formulation, and manufacturing process
Packaging, labeling, and storage conditions
Quality control and batch release testing
Nonclinical (Preclinical) Data
Pharmacology Studies – Mechanism of action, efficacy in animal models
Toxicology Studies – Safety data in animals
Carcinogenicity, Reproductive Toxicity
Clinical Data (Human Trials) – Efficacy &
Safety
Summary of Clinical Studies – Overview of Phase I, II, and III trial results
Study Reports:
Study design, methods, statistical analysis, and results
Adverse events and safety findings
Comparison with existing treatments (if applicable)
Integrated Analysis of Efficacy and Safety
Risk-Benefit Assessment
Clinical Pharmacology Data
Pharmacokinetics (PK)
Pharmacodynamics (PD)
Drug-Drug Interaction Studies
Other Important Sections
Risk Evaluation and Mitigation Strategies (REMS) – If special safety
measures are needed
Post-Marketing Study Commitments – If additional strategies are planned
after approval
Abbreviated New Drug Application (ANDA)
• An Abbreviated New Drug Application (ANDA) is submitted to the FDA
to gain approval for a generic drug. Unlike an NDA, an ANDA does not
require clinical trials to demonstrate safety and efficacy. Instead, it must
prove bioequivalence to an already approved brand-name drug (reference
listed drug, or RLD).
Administrative & Product Information
Application cover form
Proposed Drug Labeling – Should be identical to the reference listed drug (RLD)
Patent Certification & Exclusivity Information:
Paragraph I – No patents listed for RLD
Paragraph II – All patents expired
Paragraph III – Applicant will wait for patent expiry before marketing
Paragraph IV – Patent challenge (may lead to 180-day market exclusivity for the first filer)
Chemistry, Manufacturing, and Controls
(CMC) Data
Drug Substance Information:
Active pharmaceutical ingredient (API) details
Source, manufacturing process, and analytical methods
Drug Product Information:
Formulation and composition
Manufacturing process, quality control tests, and batch records
Stability studies and storage conditions
Bioequivalence (BE) Studies
Pharmacokinetic (PK) Studies
Cmax, Tmax, AUC (Area Under the Curve) comparison
In Vitro Dissolution Studies:
Inactive Ingredients & Quality Compliance
Comparison with RLD ingredients
Impurities and Stability Data
Drug Master File (DMF)
• A Drug Master File (DMF) is a confidential document submitted to the
FDA that provides detailed information about the manufacturing, quality,
and safety of a drug substance, excipient, packaging material, or drug
product. It allows manufacturers to protect proprietary data while still
permitting regulatory agencies to review it for drug approvals.
Types of DMFs:
Type I – Manufacturing Site, Facilities, and Operating Procedures
Type II – Drug Substance, and Drug Product
Type III – Packaging Materials
Type IV – Excipients, Colorants, Flavors, and Extracts
Type V – FDA-accepted Reference Information
Note
DMF is not mandatory but is often used to support NDAs, and INDs etc.
The holder of a DMF does not get FDA approval; it is referenced by applicants
for regulatory submissions.
Active Substance Master File (ASMF)
• An Active Substance Master File (ASMF) is the European equivalent of a
DMF, submitted to the European Medicines Agency (EMA). It contains
detailed information about the active pharmaceutical ingredient (API).
Structure of an ASMF
Applicant’s Part (AP, Open Part) – Contains non-confidential information
needed by the marketing authorization holder (MAH).
Restricted Part (RP, Closed Part) – Contains proprietary manufacturing
details that only regulatory authorities can review.
Clinical Trial Application (CTA) in the EU
• A Clinical Trial Application (CTA) is the European equivalent of an
Investigational New Drug (IND) application in the U.S. It is submitted to
regulatory authorities in EU member states and requires approval before
starting human clinical trials.
• Clinical Trials Information System (CTIS) is the single portal for submitting
CTAs in the EU.
Administrative Information
Application form with trial details
Sponsor and investigator contact details
Investigational Medicinal Product (IMP)
Data
Investigational Medicinal Product Dossier (IMPD), including:
Drug substance and drug product information
Manufacturing and quality control (CMC data)
Stability studies
Pharmaceutical details, including formulation, packaging, and labeling
Comparator information
Nonclinical (Preclinical) Data
Pharmacology studies
Toxicology studies
Genotoxicity and carcinogenicity studies
Clinical Trial Protocol
Objectives, study design, and methodology
Dosing regimen and administration details
Patient inclusion/exclusion criteria
Safety monitoring plan and adverse event reporting
Statistical analysis methods
Investigator’s Brochure (IB)
Summary of data
Safety profile and known risks of the drug
Dosage and administration guidelines
Risk Assessment and Ethics Compliance
Risk-benefit assessment
Compliance with Regulatory guidelines
Informed Consent Documents (ICD) for trial participants
Good Manufacturing Practice (GMP)
Certificate
• Document that shows product is manufactured in compliance with GMP
Marketing Authorization Application (MAA)
Submission for New Drug Approval
• A Marketing Authorization Application (MAA) is submitted to the
European Medicines Agency (EMA) or national regulatory authorities to
gain approval for a new drug in the European Union (EU). It is the EU
equivalent of the New Drug Application (NDA) in the U.S.
Administrative & Product Information
Application form
Proposed Summary of Product Characteristics
Patient Information Leaflet (PIL) and Packaging Label
Risk Management Plan (RMP)
Good Manufacturing Practice (GMP) certificates
Patent and exclusivity information
Summaries
Overall Summary of quality, nonclinical, and clinical data
Quality (CMC) Summary
Nonclinical Summary (pharmacology, toxicology, safety studies)
Clinical Summary (efficacy, safety, risk-benefit analysis)
Quality (Chemistry, Manufacturing, and
Controls – CMC)
Drug Substance Information
Active Pharmaceutical Ingredient (API) details
Manufacturing process and controls
Stability data
Drug Product Information
Composition and formulation
Manufacturing process and batch records
Packaging and labeling
In-process and finished product quality controls
Nonclinical (Preclinical) Data
Pharmacology Studies
Mechanism of action (MOA)
Pharmacodynamics
Toxicology Studies
Genotoxicity, carcinogenicity, reproductive toxicity
Pharmacokinetic Studies
Clinical Data (Efficacy & Safety)
Clinical Study Reports (Phase I, II, III trials)
Pharmacokinetics (PK) and Pharmacodynamics (PD) Data
Efficacy Results
Safety Data Benefit-Risk Analysis
Generic drug product approval
Article 10 of Directive 2001/83/EC is part of the Marketing Authorization
Application (MAA) framework in the EU. It defines the abbreviated
pathways for the approval of generic
While new active substances require a full MAA, generic drugs can be
approved through a simplified MAA under Article 10, which reduces the
need for extensive clinical and nonclinical studies.
Details to be submitted
Application form
Reference medicinal product details
PIL (Patient Information Leaflet), and labeling
Bioequivalence study summary
Drug substance and drug product details
Manufacturing and stability data
Bioequivalence study report (main requirement for generics)
Clinical Trial Application (CTA) – Form CT-04
Required for obtaining permission to initiate clinical trials in India.
Mandatory for new chemical entities (NCEs), vaccines, and new
indications.
Pharmaceutical companies, research organizations, academic institutions,
or investigators conducting clinical trials in India.
Key Requirements for Submission:
1. Form CT-04 (Application for Clinical Trial Permission).
2. Investigational New Drug (IND) Dossier, including:
o Preclinical (animal study) data and Investigator qualifications and site details.
o Chemistry, Manufacturing & Controls (CMC) data.
o Investigators Brochure (IB).
o Proposed clinical trial protocol.
3. Ethics Committee (EC) Approval.
• Risk-benefit assessment report
New Drug Application (NDA) – Form 44
Required for marketing authorization of new drugs in India.
Covers new chemical entities (NCEs), vaccines, and new indications of
approved drugs.
Pharmaceutical companies seeking to introduce a new drug to the Indian
market.
Key Requirements for Submission
Form 44 (Application for New Drug Approval).
Preclinical Data: Animal studies, toxicity studies.
Clinical Trial Data: Phase I-III clinical trial results.
Chemistry, Manufacturing & Controls (CMC) Data:
Drug formulation details.
Stability studies.
Impurity profiles.
Key Requirements for Submission
Labelling & Packaging Details.
Proposed Prescribing Information (Package Insert, Dosage, Warnings).
Pharmacovigilance Plan (PVP) for post-marketing surveillance.
Generic Drug Approval – Form 44 with Bioequivalence (BE)
Data
Required for approval of generic drugs (lower-cost alternatives to brand-
name drugs).
Unlike NDA, clinical trials are not needed, only bioequivalence (BE)
studies.
Pharmaceutical companies producing generic drugs of an already
approved reference product (innovator drug).
Key Requirements for Submission:
Form 44 (Application for Generic Drug Approval).
Bioequivalence (BE) Study Data:
BE studies compare the generic drug to the Reference Listed Drug (RLD).
Conducted in healthy volunteers.
Parameters measured: Maximum plasma concentration (Cmax), Time to reach Cmax
(Tmax), and Area Under the Curve (AUC).
CMC Data (Manufacturing, Stability, Impurities Analysis).
Labeling & Packaging Information (must be identical to the reference drug).
