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

Versus

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 HistoryA. Basic timeline: 1848-1968B. Events and Legislation Underlying

the Evolution and Scope of the FDADrug Importation Act (1848)>>>> Bioterrorism Act (2002)

CHAPTER 2 - CONTINUED

II.What the FDA RegulatesA. Food

CHAPTER 2 - CONTINUED

II. What the FDA Regulates – Continued

B. Drugs

CHAPTER 2 - CONTINUED

II.What the FDA Regulates – Continued

C.Medical DevicesE.g. Contact Lenses

CHAPTER 2 - CONTINUEDII. What the FDA Regulates –

ContinuedD. 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. BackgroundFDA is a federal science-based law

enforcement agency within the US Department of Health and Human Services (HHS)

II. OrganizationFDA consists of six centers and several

offices

CHAPTER 4 - PROCESS OF DRUG DEVELOPMENT

I. Introduction Definition of new drugII. Requirements

a.Preclinical Investigationb.INDc.Phase I clinical trialsd.Phase II clinical trialse.Phase III clinical trialsf.NDA

CHAPTER 4 - CONTINUEDIII.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. anti-thrombin 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. IntroductionA submission to the FDA that requests

permission to initiate a clinical study of a new drug in the United States

II. Requirement for an INDNew drug or change in use of old drug

CHAPTER 5 - CONTINUEDIII. Pre-IND MeetingBetween sponsor and FDAIV. Format of an INDV. Assembly and Submission of an

INDVI.Overview of Review Process

CHAPTER 6 - FORMATTING, ASSEMBLING AND

SUBMITTING THE NEW DRUG APPLICATION (NDA)

I. IntroductionApproval of NDA (BLA for biologics)

required for marketing and sale of drug

II. Format, Assembly and Submission of NDA

CHAPTER 6 - CONTINUEDIII. 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 – CONTINUEDI. IntroductionII. Classification of a Medical

DeviceIII. Regulatory Requirements for

Medical Devices

CHAPTER 8 - MEETING WITH FDA

I. IntroductionII. Types of FDA MeetingsIII.Categories of FDA Meetings

Type A, Type B and Type CIV.Preparing for FDA MeetingsV. Conduct at FDA Meetings

CHAPTER 9 - GOOD CLINICAL PRACTICES

I. IntroductionII. Regulations and Guidance for

GCPs

CHAPTER 10 - THE ROLE OF GOOD MANUFACTURING PRACTICES

I. IntroductionA. Regulations for Good Manufacturing

Practices (GMP)B. Current Good Manufacturing

Practices (cGMP)

II. RegulationsA. BasisB. Code of Federal Regulations (CFR)

CHAPTER 11 - POST-MARKETING 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 post-marketing surveillance

• Inspection: investigators look for evidence of non-compliance with

• Various types of inspections• Documentation: 482, 483, 484, EIR• Warning Letters

cGMP

CHAPTER 12 - FDA INSPECTION AND 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 PatentII.How an Invention is PatentableIII.The Role of Patents

CHAPTER 15 - APPLICATION OF CURRENT GOOD

MANUFACTURING PRACTICES

I. IntroductionII. 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. PlumbingV. LightingVI. Sewage and RefuseVII. SanitationVIII. Maintenance 

CHAPTER 17 - RECEIVING AND QUARANTINE

OPERATIONS

I. IntroductionII. General RequirementsIII.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. IntroductionII. Design

CHAPTER 19 - EQUIPMENT PREPARATION AND ASSEMBLY

I. IntroductionII. Equipment CleaningIII.Sanitary Versus Non-Sanitary

FittingsIV.Notes on Selected Equipment

CHAPTER 20 - CLEANING, DECONTAMINATION AND

SANITATION (CDS)

I. IntroductionII. CDS of the General

Manufacturing AreaIII.CDS of Process

Equipment

CHAPTER 20 - CONTINUED

CHAPTER 21-STERILIZATION OF PROCESS EQUIPMENT

I. IntroductionII. Methods of Sterilization

CHAPTER 21- CONTINUED

III. Validationa) Introductionb) Qualification and Validationc) Equipment Controls and

Instrument Calibration

CHAPTER 22 - PRODUCT FORMULATION AND FILLING

OPERATIONS

I. IntroductionII. Bulk Freeze-ThawingIII.Formulation ProcessIV.Sterile Filtration

CHAPTER 22 - CONTINUED

V. FillingLiquid Filling Machine with 40 to 55 Bottles/Minute Capacities and 90 to 520mL Filling Range

CHAPTER 23 - HOLDING AND DISTRIBUTION

I. IntroductionII. Warehousing ProceduresIII.Distribution Procedures

THE ENDTHANK YOU!