BIO 221 REGULATORY
COMPLIANCE IN
BIOMANUFACTURING
CHAPTER SUMMARIES
DRUGS
MEDICAL
DEVICES
BIOLOGICS
CHAPTER 1 - THE HISTORY OF THE
DEVELOPMENT OF REGULATORY
AGENCIES
I. State versus Federal Powers
and the Regulation of
Commerce
Georgia State
Capitol
The United States
Capitol
CHAPTER 1 - CONTINUED
• The United States is a federal system of
government with powers divided
between the states and the federal
government.
• The United States Constitution grants
to the federal government the power to
regulate international and interstate
commerce. Hence food and drug laws
require that the product, or at least one
of its ingredients, travel in interstate
commerce.
CHAPTER 1-CONTINUED
II.Separation of Powers
CHAPTER 1-CONTINUED
III. History of Key Regulatory
Agencies and Legislation
Underpinning Regulation
•
USDA (formed in 1862), FDA
(formed in 1931) & EPA (formed in
1970).
CHAPTER 2 - EVOLUTION AND
SCOPE OF THE FDA
I. FDA History
A. Basic timeline: 1848-1968
B. Events and Legislation Underlying
the Evolution and Scope of the FDA
Drug
Importation Act
(1848)>>>>
Bioterrorism Act
(2002)
CHAPTER 2 - CONTINUED
II.What the FDA Regulates
A. Food
CHAPTER 2 - CONTINUED
II.What the FDA Regulates –
Continued
B. Drugs
CHAPTER 2 - CONTINUED
II.What the FDA Regulates –
Continued
C. Medical Devices
E.g. Contact
Lenses
CHAPTER 2 - CONTINUED
II.What the FDA Regulates –
Continued
D. Biologics
E. Veterinary Products
CHAPTER 2 - CONTINUED
II.What the FDA Regulates –
Continued
F. Cosmetics
CHAPTER 2 - CONTINUED
II.What the FDA Regulates –
Continued
G. Radiation-Emitting Products
III.What the FDA Does Not
Regulate
CHAPTER 2 - CONTINUED
IV.Summary of the Mission and
Fundamental Activities of the
FDA
FDA Website:
http://www.fda.gov/
CHAPTER 3 ORGANIZATION OF THE
FDA
I. Background
FDA is a federal science-based law
enforcement agency within the US
Department of Health and Human
Services (HHS)
II.Organization
FDA consists of six centers and several
offices
CHAPTER 4 - PROCESS OF
DRUG DEVELOPMENT
I. Introduction
Definition of new drug
II.Requirements
a.Preclinical Investigation
b.IND
c.Phase I clinical trials
d.Phase II clinical trials
e.Phase III clinical trials
f.NDA
CHAPTER 4 - CONTINUED
III.Notes
• Biologics (BLA vs NDA; CDER or CBER):
i. Vaccines, antitoxins, sera, blood and
blood products.
ii. Therapeutic protein drugs derived
from natural sources, e.g. antithrombin III, or biotechnology, e.g.
proteins derived using recombinant
DNA technology.
iii. Gene or somatic cell therapies.
CHAPTER 5 - FORMAT,
ASSEMBLY AND
SUBMISSION OF IND
I. Introduction
A submission to the FDA that requests
permission to initiate a clinical study
of a new drug in the United States
II.Requirement for an IND
New drug or change in use of old drug
CHAPTER 5 - CONTINUED
III. Pre-IND Meeting
Between sponsor and FDA
IV. Format of an IND
V. Assembly and Submission of an
IND
VI.Overview of Review Process
CHAPTER 6 - FORMATTING,
ASSEMBLING AND
SUBMITTING THE NEW
DRUG APPLICATION (NDA)
I. Introduction
Approval of NDA (BLA for biologics)
required for marketing and sale of
drug
II.Format, Assembly and
Submission of NDA
III.
CHAPTER 6 - CONTINUED
Overview of Review Process
NDA Review Chart
The New Drug
Development
Process:
Steps from Test
Tube to New Drug
Application Review
CHAPTER 7 – MEDICAL
DEVICES
CHAPTER 7 – CONTINUED
I. Introduction
II.Classification of a Medical
Device
III. Regulatory Requirements for
Medical Devices
CHAPTER 8 - MEETING
WITH FDA
I. Introduction
II.Types of FDA Meetings
III.Categories of FDA Meetings
Type A, Type B and Type C
IV.Preparing for FDA Meetings
V. Conduct at FDA Meetings
CHAPTER 9 - GOOD
CLINICAL PRACTICES
I. Introduction
II.Regulations and Guidance for
GCPs
CHAPTER 10 - THE ROLE OF
GOOD MANUFACTURING
PRACTICES
I. Introduction
A. Regulations for Good Manufacturing
Practices (GMP)
B. Current Good Manufacturing
Practices (cGMP)
II.Regulations
A. Basis
B. Code of Federal Regulations (CFR)
CHAPTER 11 - POSTMARKETING REGULATION
• Adverse drug reports are required to
be reported to FDA
• Post-Marketing Surveillance is an
ongoing process by FDA for
monitoring the safety of medical
products
• MedWatch, the FDA Medical
Products Reporting Program, was
established to facilitate postmarketing surveillance
CHAPTER 12 - FDA
INSPECTION AND WARNING
LETTERS
•
Inspection: investigators look for
evidence of non-compliance with
c
•
•
•
Various types of inspections
Documentation: 482, 483, 484, EIR
Warning Letters
CHAPTER 13 - RISK-BASED
APPROACH TO FDA
REGULATION OF GMP
•
•
•
GMP regulations broad and open to
some interpretation
Risk-based approach
Initiative: Pharmaceutical Quality
for the 21st Century: A Risk-Based
Approach
CHAPTER 14 – PATENTS AND
THEIR ROLE IN DISCOVERY
AND MARKETING
I. The Patent
II.How an Invention is Patentable
III.The Role of Patents
CHAPTER 15 - APPLICATION
OF CURRENT GOOD
MANUFACTURING
PRACTICES
I. Introduction
II.CGMP Procedures
CHAPTER 16 - BUILDINGS
AND FACILITIES FOR GMP
I. Design and Construction
CHAPTER 16 - CONTINUED
II. Plant Materials
CHAPTER 16 - CONTINUED
III. Ventilation, Air Filtration; Air
Heating and Cooling
CHAPTER 16 - CONTINUED
IV. Plumbing
V. Lighting
VI. Sewage and Refuse
VII. Sanitation
VIII. Maintenance
CHAPTER 17 - RECEIVING
AND QUARANTINE
OPERATIONS
I. Introduction
II. General Requirements
III.Receipt and Storage of Untested
Components, Drug Product
Containers and Closures
IV.Testing and Approval or Rejection
of Components, Drug Product
Containers and Closures
CHAPTER 17 - CONTINUED
V. Use of Approved Components,
Drug Product Containers, and
Closures
CHAPTER 17 - CONTINUED
VI.Retesting of Approved
Components, Drug Product
Containers, and Closures
VII.Rejected Components, Drug
Product Containers, and
Closures
VIII.Drug Product Containers and
Closures
CHAPTER 18 - CLEAN
ROOMS
I. Introduction
II.Design
CHAPTER 19 - EQUIPMENT
PREPARATION AND
ASSEMBLY
I. Introduction
II.Equipment Cleaning
III.Sanitary Versus Non-Sanitary
Fittings
IV.Notes on Selected Equipment
CHAPTER 20 - CLEANING,
DECONTAMINATION AND
SANITATION (CDS)
I. Introduction
II.CDS of the General
Manufacturing Area
III.CDS of Process
Equipment
CHAPTER 20 - CONTINUED
CHAPTER 21STERILIZATION OF
PROCESS EQUIPMENT
I. Introduction
II.Methods of Sterilization
CHAPTER 21- CONTINUED
III. Validation
a) Introduction
b) Qualification and Validation
c) Equipment Controls and
Instrument Calibration
CHAPTER 22 - PRODUCT
FORMULATION AND
FILLING OPERATIONS
I. Introduction
II.Bulk Freeze-Thawing
III.Formulation Process
IV.Sterile Filtration
CHAPTER 22 - CONTINUED
V. Filling
Liquid Filling Machine with 40 to
55 Bottles/Minute Capacities and
90 to 520mL Filling Range
CHAPTER 23 - HOLDING
AND DISTRIBUTION
I. Introduction
II.Warehousing Procedures
III.Distribution Procedures