CANADIAN CDMO IN A WORLD DOMAIN OF PHARMACEUTICAL DEVLOPMENT Dr. - - PowerPoint PPT Presentation

▶
canadian cdmo in a world domain of pharmaceutical
SMART_READER_LITE
LIVE PREVIEW

CANADIAN CDMO IN A WORLD DOMAIN OF PHARMACEUTICAL DEVLOPMENT Dr. - - PowerPoint PPT Presentation

Mar 12, 2023 19 likes •342 views

CANADIAN CDMO IN A WORLD DOMAIN OF PHARMACEUTICAL DEVLOPMENT Dr. Boris Gorin, Alphora Research Inc. October, 2020 Recent Trends in Pharma Outsourcing Overall increase of outsourcing to CDMO across the industry Big Pharma shift their

slide-1
SLIDE 1

CANADIAN CDMO IN A WORLD DOMAIN OF PHARMACEUTICAL DEVLOPMENT

  • Dr. Boris Gorin, Alphora Research Inc.

October, 2020

slide-2
SLIDE 2

Recent Trends in Pharma Outsourcing

❑ Overall increase of outsourcing to CDMO across the industry ❑ Big Pharma shift their outsourcing from Asia back to NA and Europe ❑ Focus on QbD and DoE driven development ❑ One-site vs One-stop shop model of service ❑ Fast Track product development programs

Sources: C&EN, May 21, 2018 Contract Pharma, January11, 2019

slide-3
SLIDE 3

Why CDMO?

❑ Economical incentives ❑ Operational flexibility and responsiveness ❑ Increasing segment of virtual pharma ❑ Vast expertise in variety of pharmaceutical products ❑ Adoption of new technologies for development and manufacture

slide-4
SLIDE 4

4

Our mission:

Innovation-driven contract development and manufacturing

  • rganization (CDMO) focused on developing technologies for

manufacture of pharmaceutical substances and drug products

▪ History

➢ Established in 2003 as private enterprise ➢ Acquired by Eurofins in June 2017

▪ Team

➢ Total of approx. 170 people ➢ 30 Ph.D. chemists ➢ 115 scientists, engineers and support staff

▪ Experience

➢ Developed hundreds of unique processes for making Active Pharmaceutical

Ingredients for pre-clinical, clinical and commercial

Eurofins Alphora

slide-5
SLIDE 5

5

Right Development at Right Time

Pre-Clinical Development Commercialization & Approval Clinical Trials: Phase I - III Route Selection Route Development Non-GMP Manufacture Critical Parameters cGMP Manufacture CMC Preparation Process Optimization Medicinal Chemistry

Concept Development Lead Optimization

Ref Std, Impurities, Metabolites Method Development Specification Development In Process Controls Method Validation Stability Studies

slide-6
SLIDE 6

Process Chemistry

slide-7
SLIDE 7

Process R&D Expertise

✓ Route Scouting ✓ Process Scale-up Development ✓ Design of Experiments (DoE) ✓ Critical Process Parameter Study ✓ Validation Preparation ✓ Impurity Marker Synthesis ✓ Fate and Purge Studies ✓ Process Safety Evaluation ✓ Structure Elucidation ✓ Solid Forms Study

7

slide-8
SLIDE 8

Process R&D Technologies and Tools

8

❑ High Throughput Screening

▪ Unchained Junior™ 96 wells HTS

❑ Parallel reactor systems

▪ HEL Polyblock™ 8 wells system ▪ Mettler EasyMax 420 and EasyMax102

slide-9
SLIDE 9

Process R&D Technologies and Tools

9

❑ Preparative Chromatography (mg to kg) ❑ 0.5 – 4 L Parr™ Hydrogenetors ❑ Wipe-Film Distillation ❑ Spray and Freeze Drying

slide-10
SLIDE 10

Process R&D Technologies and Tools

10

❑ Flow Chemistry ▪ Vapourtec™ plug-flow reactor ▪ LabtrixTM for R&D Scale microreactor ▪ KilotrixTM for cGMP Kilolab Scale

slide-11
SLIDE 11

❑ HPAPI Isolators

  • Compounds to Safebridge Class 4, OEL’s <30 ng/m³
  • Isolator containment, Bag-in-bag-out technology
  • Air Monitoring / surrogate testing

11

Process R&D Technologies and Tools

slide-12
SLIDE 12

Process Safety Assessment Tools

12

❑ Calorimetry

▪ HEL Thermal Screening Unit ▪ Phi-Tec™ Adiabatic calorimeter ▪ Simular™ reaction Calorimeter

slide-13
SLIDE 13

Process R&D scale-up capabilities

Kilo Labs ▪

20-30-50 L Glassware

▪

30 L Buchi reactors

▪

  • 80 to 200°C

▪

4-20 L Hydrogenators

▪

5-kg cartridge Biotage LC

▪

2’-3’ Prep-HPLC

13

slide-14
SLIDE 14

Solid State Analytical

❑Solid Form Characterization:

▪

Polymorphism and crystallinity study

▪

Particle size distribution

▪

Thermogravimetric analysis

▪

Dynamic Vapour Sorption

▪

Light and Electron microscopy

Bruker D8 DISCOVER HTS unit for high-throughput screening

14

slide-15
SLIDE 15

Solid State Development

❑API Solid Form Development:

▪

Polymorph screening and development

▪

Pharmaceutical salt screening and development

▪

Solvates and co-crystals screening

▪

Particle size engineering

▪

Crystallization scale-up development Unchained Labs Junior™ HTS robot

15

slide-16
SLIDE 16

Analytical Development

slide-17
SLIDE 17

GMP Analytical Services

  • Method qualification and validation

➢ Phase appropriate ➢ Forced Degradation Studies ➢ Photostability Studies ➢ QbD Method Development - FUSION

software

  • Identification, Characterization, &

Qualifications

➢ Starting materials, intermediates,

impurities & API’s

  • In-Process Controls
  • Fate of Impurities Study
  • Reference Standard Preparation and

Qualification

  • Development of methods for pGTI’s

(ppm & ppb levels)

➢ GCMS ➢ LCMS

  • Non-Chromophore API’s and

intermediates

➢ Evaporative Light Scattering (ELS) ➢ Mass Spec ➢ Flame ionisation detector (FID) ➢ Electron capture detector (ECD) ➢ Charged aerosol detection (CAD)

(2018)

  • Method Transfers
slide-18
SLIDE 18

GMP Stability

  • ICH Stability Studies – all Climatic Zones,

(I – IVa)

  • Photo Stability (ICH Q1B)
  • Accelerated Stability
  • Forced Degradation Studies
  • Trending Studies and Reporting
  • Vaisala Central Monitoring System
  • Our stability programs are strictly

controlled using 21CFR, part 11

18

slide-19
SLIDE 19

Kilo Lab & Manufacturing Plants

slide-20
SLIDE 20

Kilo Labs - GMP

2 Kilo Labs (up to Cat 3b) 1 Kilo Lab (Cat 4):

  • 2 X 50L Glassware
  • 2 X 60L Glassware
  • 80 to 200°C
  • 20L Hydrogenations
  • Enclosed Filtration & Drying Systems
  • Biotage
  • Prep-HPLC
slide-21
SLIDE 21

Manufacturing Plant - GMP

2 Manufacturing Suites (up to Cat 3b):

  • 3 X 200L Reactors
  • 3 X 500L Reactors
  • 80˚C to 200˚C
  • Hydrogenations
  • Enclosed Filtration & Drying Systems
  • Biotage
  • Prep-HPLC
  • Vaisala Central Monitoring System

21

slide-22
SLIDE 22

API Commercialization Support

22

  • CMC Gap Analysis and Risk Assessment
  • Impurities Markers Synthesis
  • Fate and Purge Studies
  • Full Structure Characterization and

Elucidation

  • Process Optimization
  • Critical Process Parameters Assessment
  • Design of Experiments; QbD
  • Supply Chain Management
  • Preparation for, and execution of process

validation

  • Continuing CMC support during and after

market launch

slide-23
SLIDE 23

Pre-formulation and Formulation Development

slide-24
SLIDE 24

Bridging the gap

24

API Drug Product API Drug Product

SSRD

slide-25
SLIDE 25

SSRD & Pre-Form: Synergy & Overview

Solid State Chemistry Physicochemical Characterization Pre-Formulation Solubility/Absorption/ /Excipient Compatibility/Stability Solid State Screening Salt, Solvate & Polymorph Screening/Optimization

API Development & Manufacturing Drug Product Dev . & Clinical MFG

API Physical Property Engineering

25

slide-26
SLIDE 26

API Solid Form R&D

High-throughput Screening for Discovery

Polymorph Salt Solvate Co-crystal

Solid State Characterization

PXRD PSD SEM DVS FT-IR

Crystallization Process Development

Solubility Metastable Zone FBRM

SSRD Capabilities

26

slide-27
SLIDE 27

High-Throughput Screening (HTS)

➢ High-throughput allows quick execution of hundreds of tests using minimum amounts

  • f chemicals

➢ Screening for salts and co-crystals ➢ Crystallization and polymorph screening ➢ Robotic equipment capable of liquid transfers, hot filtration, temperature cycling, stirring and grinding

27

slide-28
SLIDE 28

Candidate Ranking PION: Solubility & Permeability Pion System

28

slide-29
SLIDE 29

Drug Product Operations

  • Formulation Development

29

slide-30
SLIDE 30

Drug Product Facility (2020)

30

Key Features

  • High potent capability
  • Humidity control
  • ISO Class 8 certified/validated
  • Independent development suites
slide-31
SLIDE 31

31

Fully Integrated Service one-site CDMO

Pre-Clinical Development Commercialization & Approval Clinical Trials: Phase I - III Non-GMP & cGMP Manufacture, Process Validation CMC Preparation & Filing Medicinal Chemistry

Concept Development Lead Optimization

Synthetic and Process Development Analytical Development & Validation, Stability Studies Pre-Formulation & Formulation Development

slide-32
SLIDE 32