2 Day "Regulation of Biologics" Training Course II

The following is an overview of the 2 day Training Course II:

Day 1

Here are the subjects covered on Day 1 ...

• Definition of a Biologic
• Method of preparation of a biologic
• Differences between biologics and conventional pharmaceutics
• Schedule D Drugs
• Food and Drugs Act & Regulations
• Part C Drugs
• Division 1 - General
• Division 2 - GMP
• Division 4 - Schedule D Drugs
  • General
  • Bacterial
  • Viral
  • Toxins, toxoids
• Division 5 - Drugs for Clinical Trials Involving Human Subjects
• Division 8 - New Drugs and New Drug Submission
• World Health Organization (WHO)
• WHO Requirements for a National Regulatory Authority
• Canadian Regulatory Authority for Biologics
  • Organization - BGTD
  • CBE and CERB
• Activities of CBE and CERB
• Regulatory life cycle of a Biologic
  • Drug development phases
  • Submission phases
• Review Process for biologics
• Key Review Outcomes
• BGTD Submissions in 2000
• Lot Release/Definition
• Essentials of a Lot Release System
• Factors considered in lot release
• Product Indication
• Well Characterized Products
• Other factors determining lot release
• Characterization of Products for Lot Release
  • Category 1, 1A, 2, 3 and 4
• BGTD Lot Release in 2000
• Post Market Review
  • SNDS and NC
• Post Market Assessment
  • ADR reporting

Part 2 - Pre-Clinical/Clinical

• Drug Development Phases
  • Research, pre-clinical, clinical, market
• Process Development
• In-Process controls
  • Critical decision making steps
  • Limits
• Production stages
• Clinical Trial Material
• Product characterization/product specifications
• Analytical Methods and specifications
  • Acceptance criteria
  • Limits
• Different levels of production
• Pilot Plant
• Pre-Clinical studies
• Primary Goals of Pre-Clinical Studies
• In vitro studies
• In vivo studies
• Types of pre-clinical studies
  • Safety pharmacology
  • Toxicology single dose and repeat dose
  • Phamacokinetic
  • Local tolerance
  • Genotoxicity
  • Carcinogenicity
  • Reproductive toxicity
• Good Laboratory Practice (GLP)
  • General
  • Definition
• GLP categories
  • Organization
  • Personnel
  • Facilities
  • Equipment
  • Testing facilities operation
  • Reagents
  • Test samples
  • Methods/SOPs
  • Protocol
  • Records and reports
• Quality Assurance Program
• Clinical Trials
• Division 5 Regulation for Clinical Trials
• Why do Clinical Trials
• Clinical Trial Requirements in Canada
• Types of Clinical Trials
  • Purpose, Population size Outcome measure and design for:
  • Phase 1
  • Phase 2
  • Phase 3
  • Post Market
• Div 5 Clinical Trial Application (CTA) and amendment (CTAA)
• Filing of a CTA for a Marketed drug
• Clinical Trial Ammendment Application
• Changes requiring a new CTA vs. a CTA-A
• Clinical Trial Application CTD format
• Investigators Brochure
• C.05.010 (j) GMP requirement for clinical trials
• CT labeling

Part 3 - Production Process for Biologics

• Drug Substance
• Cultivation/fermentation
• Seed propagation: master seed, working seed
  • Cell propagation
  • Major parameters controlled during fermentation; oxygen supply, mixing
  • Modes of fermentation
  • Batch
  • Fed batch
  • Continuous
  • Growth phases
• Purification
  • Harvest
  • Clarification
  • Centrifugation
  • Cross flow membrane filtation
  • Cell separation/broth separation
  • Cell disruption
  • Drug substance isolation methods
  • Precipitation
  • Chromatography
  • UF
• Intermediates
  • Conjugate vaccines
  • Acellular pertussis
• Adsorption
• Purification suite
• Chromatographic columns
• Filtration; integrity testing
• Inactivation
• Impurities
• Manufacturing areas
  • Controlled areas
  • Non-controlled areas
  • Manufacturing suite
• Containment
  • Primary
  • Secondary
• Design considerations for containment
  • Flows of raw materials, personnel, product, waste
• Air Handling systems for containment
• Biological safety cabinets
• Biological Agents by Risk Group
  • Factors for classification of risk group
  • Risk group levels 1 to 4
  • Additional factors for determining containment level
• Risk Group 1 Containment Level Requirements
• Risk Group 2 Containment Level Requirements
• Risk Group 3 Containment Level Requirements
  • Air Handling Level 3
  • HEPA filtration
• Clean Room
  • General
  • Clothing
  • Classification/Grades of Clean room A to D (100 to 100,000)
• Environmental Standards for Clean Rooms
  • Particulate requirements
  • Microbial requirements
• Class requirements for particular operations
• Environmental Monitoring
• Surveillance Monitoring Program
  • Sample site selection
  • Sampling frequency
  • Alert and action levels
  • Identification of micr-organisms
• Air sampling for particulates
• Microbial evaluation of air
• Methods for evaluation of air
• Techniques for microbial evaluation of surfaces
• Representative sampling system/sites

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Day 2

Here are the subjects covered on Day 2 ...

Part 1 - GMP

• Good Manufacturing Practice
  • Definition
  • Quality control basic requirements
  • Quality management
  • Guiding principle of GMP
  • Factors to be controlled for consistency
• GMP basic requirements
• GMP categories Div 2 regulation
• Establishment licensing
• Inspection
• On Site Evaluation for Biologics (OSE)
• Stages of an inspection/OSE
• Exit Notice
• OSE issues
• Risk Definitions for Exit Notice Observations
  • Risk 1, 2 or 3
• Typical GMP Definition, Requirements and Risk Observations found for
  • Premises
  • Equipment
  • Personnel
  • Sanitation
  • Raw Material Testing
  • Manufacturing Control
  • Quality Control Department
  • Packaging Material Testing
  • Finished Product Testing
  • Records
  • Samples
  • Stability

Part 2 - Validation

• Validation - Definition
• Qualification/Validation Program
• Validation - Product specifications
• Product Quality
• Consistency Lots
• Critical Validation Concepts
• Phases of Validation
  • Phase 1 - Pre-Validation - Qualification
  • Phase 2 - Process Validation - Performance Qualification
  • Phase 3 - Validation Maintenance
• Validation Master Plan
• Typical Master Plan for Validation
• Validation Protocol
• Calibration/ Program
• Installation Qualification
• Operational Qualification
• Performance Qualification
• Process Validation
• Types of Process Validation
  • Prospective
  • Concurrent
  • Retrospective
• Changes Requiring Re-Validation
• Method Validation Studies
• ICH Q2B Validation Analytical Methods
  • Accuracy
  • Precision
  • Specificity
  • Detection Limit
  • Quantitation Limit
  • Linearity
  • Range
• Methods for Biologics

Part 3 - Drug Submissions

• Key Review Outcomes
• Regulatory Life Cycle of a Vaccine
• Filing Information
• Management of Drug Submissions
• Definition of a submission
• Submission types
• New Drug Submission
• Priority Submission and review
• Screening
  • Impact of screening deficiencies
  • How to prevent screening deficiencies
• Policies and guidelines
• Screening Deficiencies
  • Administrative
  • Labeling
  • Quality
  • Comprehensive summary
  • Clinical

Common Technical Document (CTD) Format for Drug Submissions

• Module 1: Administrative
  • Administration/ prescribing information
  • GMP and Establishment Licensing
  • Application forms, certificates and regulatory status
  • Product labeling, inner and outer
  • Product Monograph
  • Part 1 Health Professional information
  • Part 2 Scientific Information
  • Part 3 Consumer Information

• Module 2: CTD summaries
  • Pre-clinical
  • Clinical
  • Quality

• Module 3: Quality
  • Drug Substance
  • General information
  • Nomenclature, structure, general properties (physicochemical, biological)
  • Manufacture
  • Facilities, manufacturing process, in process control, batches and scale definition, cell culture, seed culture and harvest, purification and modification reactions, inactivation, filling, storage and transportation
  • Control of materials
  • Non biological sourced raw materials, biological sourced raw materials, source, history and generation of cell/seed substrate, viral, cellular, microbial or animal and lines, primary, diploid , genetic constructs and recombinant cell lines
  • Cell banking systems and characterization (Master and Working)
  • Control of critical steps and intermediates
  • Process validation and process development
  • Characterization
  • Structure elucidation and characterization
  • Impurities (product, process)
  • Control of drug substance
  • Specifications
  • Test methods
  • Validation of analytical procedures
  • Batch analyses
  • Reference standards or materials
  • Container closure system
  • Stability
  • Data
  • Summary and conclusions (storage and dating)
  • Post approval commitment and stability protocol
  • Intermediates
  • Drug product
  • Description and composition
  • Pharmaceutical development
  • Manufacture
  • Manufacturer
  • Manufacturing process
  • Control of critical steps and intermediates
  • Process validation
  • Control of excipients
  • Specifications
  • Analytical procedures
  • Validation
  • Justification of specifications
  • Excipients of human or animal origin
  • Control of drug product
  • Specification
  • Analytical procedures
  • Validation
  • Justification of specification
  • Batch analyses
  • Characterization of impurities
  • Reference standards or materials
  • Container closure system
  • Stability
  • Data
  • Summary and conclusions (storage and dating)
  • Post approval commitment and stability protocol
  • Facilities and Equipment
  • Manufacturing flow diagrams
  • Contact equipment
  • HVAC
  • Water
  • Cleaning systems
  • Adventitious Agents Safety Evaluation
  • Viral
  • Materials of biological origin
  • Testing at appropriate stages of production
  • Viral clearance studies
  • Non-viral agents
  • Regional Information
  • Product Documentation
  • Lot Release
  • Product specific Facility Information
  • Floor diagrams
  • Manufacturing process description of areas
  • Multi-product facility
  • Changeover procedures
  • Animal facilities

• Module 4: Non-Clinical Reports
  • Table of contents
  • Literature reports
  • Study reports
  • Pharmacology
  • Pharmacokinetics
  • Toxicology

• Module 5: CTD summaries
  • Table of contents
  • Tabular listing of clinical studies
  • Study reports
  • Bio-pharmaceutic studies
  • Pharmaco-kinetic studies using human biomaterials
  • Human pharmacokinetic studies
  • Human pharmacodynamic studies
  • Efficacy and safety studies
  • Post-marketing experience
  • Case report forms
  • Chemistry and Manufacturing deficiencies
  • In manufacturing process
  • Product
  • Methods
  • Missing facility information
  • Specific Vaccine C&M deficiencies
  • Specific Biotherapeutic C&M deficiencies