Market Authorization of Biological Products in USA

Definition of Biological Products:

According to USFDA, a biological product means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings. Biological products can be composed of sugars, proteins, or nucleic acids, or a combination of these substances; or living entities, such as cells and tissues. Biological products are made from a variety of natural resources—human, animal, and micro- organism—and may be produced by biotechnology methods.

List of Therapeutic Biological Products:

Regulated by CBER


Allergenic extracts (e.g. for allergy shots and tests)



Blood, blood components, plasma derived products



Gene therapy products



Antitoxins, antivenins, and venoms



Human tissue and cellular products used in transplantation





Regulated by CDER


Monoclonal antibodies



Proteins (derived/recombinant) like Cytokines (e.g. Interferons), Enzymes (e.g. thrombolytics) etc.



Growth factors (proteins that affect the growth of a cell)



Immunomodulators (non-vaccine and non-allergenic products intended to treat disease by inhibiting or modifying a pre-existing immune response)



Proteins intended for therapeutic use that are extracted from animals or microorganisms, including recombinant versions of these products (except clotting factors)




Regulatory Pathway for Biological Products:


Overview of Contents of IND Application:

1.     IND Form FDA 1571

2.     Table of Contents

3.     Introductory Statement

4.     General Investigational Plan

5.     Investigator’s Brochure and Form 1572

6.     Protocol

a.      Study Protocol and Design

b.     Investigator Data

c.      Facilities Data

d.     IRS Data

e.      CRO Statement and Details of person responsible for evaluating drug safety

7.     Chemistry, Manufacture and Control (CMC) Data

a.      General Drug Information (Nomenclature, Structure and Properties)

b.     Manufacturer Details (Name and Address, Process, Control of Materials, Critical Process, Process validation, Manufacturing Process Development)

c.      Characterization (Proof of Structure, Impurities)

d.     Controls (Specification, Analytical Methods, Validation, Batch Analysis)

e.      Reference Standards

f.       Container Closure System

g.      Stability Data

8.     Pharmacology and Toxicology Studies Data

9.     Previous Human Experience

10.  Additional Information



[1]  Pre-IND Meeting

a.      Formal Meetings Between the FDA and Sponsors or Applicants

b.     IND Meeting for Human Drugs and Biologics

[2]  IND Application

a.      Form 1571 – IND Application

b.     Form 1572 – Statement of Investigator

c.      Exploratory IND Studies

d.     Fast Track Drug Development Program

e.      Contents and Format of IND for Phase I Studies

f.       INDs for Phase 2 & 3 Studies

[3]  Clinical Trials

a.      Early Clinical Trials with Live Biotherapeutic Products

b.     FDA acceptance of Foreign Clinical Studies not conducted under an IND

[4]  Chemistry, Manufacturing & Controls

a.      Comparability Protocol - Protein Drug Products and Biological Products

b.     Analytical Procedure & Method Validation

[5]  Product Specific Guidance:

a.      Cellular and Gene Therapy

b.     Monoclonal Antibodies

c.      Tissue based Products

d.     Vaccines

[6]  Biosimilar Products

a.      Scientific Considerations in Demonstrating Biosimilarity to a Reference Product

b.     Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product

c.      Implementation of BPCI Act 2009

[7]  BLA/351(K) Application

a.      BLA Process

b.     Form 365h – Application to Market

c.      Form 3674 – Certification of Compliance

[8]  Post-Marketing Safety Surveillance -

[9]  Changes to Approved BLA Application