Presentation: Evaluation Panel Roadshow - Overview of Chemistry Evaluations

TGA presentations: Evaluation Panel Roadshow, November 2017

8 December 2017

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Presentation

  • Presented by: Pharmaceutical Chemistry Section, Scientific Evaluation Branch
  • Presented at: Therapeutic Goods Evaluation Panel Information Sessions
  • Presentation date: November 2017
  • Presentation summary: Evaluation Panel Roadshow information for prospective evaluators for the TGA

Transcript

Overview of Chemistry Evaluations

Pharmaceutical Chemistry Section, Scientific Evaluation Branch

Therapeutic Goods Evaluation Panel Information Sessions, November 2017

Slide 1 - Requirements

  • TGA website:
    • Therapeutic Goods Act (The Act) and Regulations
    • Therapeutic Goods Orders (TGOs)
    • Australian Regulatory Guidelines for Prescription Medicines (ARGPM)
    • Adopted EU Guidelines (ICH)
    • Pharmacopoeia (BP/Ph Eur/USP)
    • Good Manufacturing Practice (GMP)

Slide 2 - Module 1 Administrative and Prescribing Information

Contains

  • Product Information
  • Labels
  • Drug Master Files (DMFs) and Certificates of Suitability (CEP)
  • Good Manufacturing Practice (GMP)
  • Compliance with pre-submission planning form and planning letter
  • Overseas regulatory status
  • Summary of bioavailability or bioequivalence studies
  • Justification for not providing appropriate biopharmaceutic studies

Slide 3 - Module 3.2.S Quality of Drug Substance

Contains

  • General information
  • Manufacture
  • Characterisation
  • Control of drug substance (API)
    • Specification (+ justification)
    • Analytical procedures (+ validation)
    • Batch analytical data
  • Reference standards/materials
  • Container closure system
  • Stability
    • Accelerated conditions
    • Long term conditions

Slide 4 - Drug Substance: DMF/CEP vs. Main Dossier

  • The main dossier must include the following in relation to the API:
    • Details of testing of the API by the finished product manufacturer
    • Relevant validation data generated by the finished product manufacturer
    • Representative batch analytical data generated by the finished product manufacturer

Slide 5 - Module 3.2.P Quality of Drug Product

  • Contains:
    • Description and composition of the drug product
    • Pharmaceutical development
    • Manufacture (including GMP)
    • Control of excipients
    • Control of drug product
      • Release and expiry specifications (+ justification)
      • Analytical procedures (+ validation)
      • Batch analytical data
    • Reference standards/materials
    • Container closure system
    • Stability
      • Stressed conditions
      • Long term conditions
      • Accelerated conditions

Slide 6 - Module 5.3.1 Biopharmaceutic Studies

  • PART A Summary of published pharmacokinetic data
    • Absorption, metabolism, in-vivo interconversion of enantiomers
    • Mode and route and rate of elimination
    • Effects of food, gender, age, smoking, genetic polymorphism
    • Active entity
    • Recommended dosage
    • Dose-response proportionality
  • PART B Summary and evaluation of study
  • Administrative information
    • Relative bioavailability
    • Study title and code, report and protocol number
    • Trial dates and site details
    • Ethics committee approval
    • Principal investigator signature

Slide 7 - Module 5.3.1 Biopharmaceutic Studies

  • PART B Summary and evaluation of study
    • Formulations compared (test and reference)
      • Batch numbers, assay, expiry date, source, strength
    • Comparative dissolution
    • Study design
    • Subject selection and demographics
    • Restrictions on subjects
    • Dropouts and withdrawals
    • Sampling times
    • Assay procedure
      • Bioanalytical and analytical methods
        • Entities, assay method, calibration standard concentration, LLOQ
      • Pre-study validation
      • Investigator’s acceptance criteria

Slide 8 - Module 5.3.1 Biopharmaceutic Studies

  • PART B Summary and evaluation of study
    • Quality control of samples
    • Reported pharmacokinetic parameters and statistical analyses
    • Recalculations of pharmacokinetic parameters and statistics
      • Tmax, AUC, Cmax, 90% CIs
      • Assessment
    • Justification for non-supply of bioavailability/bioequivalence data
    • Conclusions
  • Requirements for biopharmaceutic studies depend on the dosage form
    • Fed, fasted, in vitro/in vivo correlation and/or steady state

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