2 Day "Regulation of Biologics" Training Course I

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

Day 1

Here are the subjects covered on Day 1 ...

Why Biologics are regulated differently than pharmaceutical drugs
- Special characteristics of Biologics
- Quality evaluation phases for a Biologic
- Major concerns for production of Biologics
- In Process Control system
Biologics Legislation in Canada
- Divisions of F&D Act applicable to Biologics
- Organization Structure of Regulatory Agency in Canada for Biologics
Review Process
- Key review outcomes
- Regulatory life cycle
- Filing
- Submission types
- Management of Drug Submissions
Comparison to US (CBER) Regulation Process
Screening
- Policies and Guidelines
- Screening deficiencies - administrative, quality, clinical, labeling
Preclinical studies
Clinical Studies
- Division 5 regulations
- Types of clinical trials - phase 1, 2, 3 or 4 trials
- Clinical trial Application
- Clinical trial Amendment and Application
- Changes requiring a new Clinical Trial vs a Clinical Trial Amendment
- Investigator’s Brochure
- C.05.010 (j) GMP requirement for clinical material
- Clinical trial product labeling
New Drug Submissions
Common Technical Document (CTD) format for New Drug submissions as by ICH
Module 1 - Administrative
- administration/prescribing information
- GMP and Establishment Licensing
- Application forms, certificates and regulatory status
- Product labeling, inner and outer
- Product Monograph
Module 2 - CTD summaries
- Pre-clinical
- Clinical
- Quality
Module 3 - Quality
- Drug substance
- Drug product
- Facilities and Equipment
- Adventitious agents Safety evaluation
- Regional information; product documentation, lot release
- Product - Specific Facility Information
Module 4 - Non-Clinical Reports
- Pharmacology
- Pharmacokinetics
- Toxicology
Module 5 - Clinical Study reports
- Bio-pharmaceutic studies
- Pharmacokinetic 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
On Site Evaluation (OSE)/Inspection
- Stages of an OSE/Inspection
- OSE issues
Lot Release Program
- Definition
- Essentials of a lot release system
- Factors considered in lot release
- Categorization of products for lot release; testing and review requirements of specific groups (Group 1, 1A, 2, 3 or 4)
Post Market Review and Surveillance
Changes to Marketed Drugs

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Day 2

Here are the subjects covered on Day 2 ...

Production Process for Biologics

Seed Propagation - Master Seed and Working Seed
Cell Propagation - Master Cell Bank and Working Cell Bank
Fermentation Growth Phases
Model Legislation - Canada
Modes of Fermentation
- Batch
- Fed Batch
- Continuous
Factors Affecting Fermentation
Purification
- Cell culture harvest
- Cell separation/broth separation
- Clarification; centrifugation; filtration
- Cell disruption
- Cell supernatant/broth concentration; cross flow membrane filtration
- Intermediates; inactivation
Purification suite
- Chromatographic columns
- Filtration; integrity
- Impurities
- Downstream drug substance isolation
Formulation and filling
Labeling and Packaging

Facility Design Considerations

Primary and Secondary Containment
Risk Level of Pathogens
Containment area design and Air handling
Laboratory Testing (Optional)
Biological Safety Cabinets
Requirements for Large Scale Production Containment levels
Clean Room Concept
Classes of Clean Rooms
- Environmental Standards
- Microbial Standards
Environmental Control Parameters
Class Requirement for specific Production Operations
Surveillance/Monitoring Program
- Sampling Site Selection
- Sampling Frequency
- Alert and Action Levels
- Identification of Organisms
Methods for Microbial Evaluation of Air
- Slit to Agar impact sampler, Andersen Air (sieve) sampler, Relative Centrifugal Sampler, Cascade Impacter, Membrane filtration, Settling Plates
Surface Sampling
- RODAC plates, swabbing, agar overlay, surface rinse

Validation

Definition
Major Concerns
Product Specifications and Product Quality
Consistency Lots
Critical Validation Concepts
Phases of Validation
Validation master Plan
Validation Protocol
Calibration
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
Process Validation
Types of Process Validation
- Prospective
- Concurrent
- Retrospective
Fermentation Validation
- Fermenter Calibration
- Fermenter Components and Features / IQ
- Operational Qualification
- Performance Qualification
- CIP and Confirmation of effectiveness, criteria
- SIP and Confirmation of effectiveness, criteria
- Other Validation tests and criteria
- Fermentation Process validation
Cleaning Validation
- Definition
- Criteria for acceptance
- CIP for equipment
- Disinfectants and cleaning agents for premises
- Cleaning of Laminar Flow Hoods / Class C and D areas
- Cleaning assessment
- Canadian Cleaning Guidelines
- Types of cleaning validations
Method Validation - ICH Q2B Validation Characteristics for Analytical Methods
- Accuracy
- Precision (repeatability, intermediate precision, robustness)
- Specificity
- Detection Limit
- Quantization Limit
- Linearity
- Range
Validation of Bioassays

Good Manufacturing Practice (GMP)

Definition
Quality Control
Quality management
Factors to be controlled for consistency
GMP Basic Requirements
GMP Categories and Regulations In Canada
Risk Definitions
General Concepts, Specific Regulations and Exit Notice Observations for each of the categories
- Premises
- Equipment
- Sanitation
- Raw Material Testing
- Manufacturing Control
- Quality Control Department
- Packaging Material Testing
- Finished Product testing
- Records
- Samples
- Stability
- Sterile Products
GMP Regulations for Animal Use
- Animal Health
- Animal Facility

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