DEVELOPMENT APPROACH

1/4
 

PROCESS CHEMISTRY | The Depth to find the answers

Alphora’s R&D team operates well-equipped laboratories to address the most complex API challenges.

 

Route Development

Our chemists have a broad range of experience and knowledge of the latest technologies in organic synthesis to establish robust and economical routes for the synthesis of API’s.

 

Process Development

Our team has considerable experience with process development, successfully introducing hundreds of chemical steps to cGMP scale up and advancing several API’s to commercialization.

 

Impurities Synthesis and Control

Alphora identifies, isolates and synthesizes process related impurities to support process development, analytical control and regulatory requirements. Our tools include chromatography for the isolation of process impurities, LC/MS-MS/MS and multi-nuclear NMR for characterization. Our experience includes “Spike and Purge” studies to understand the origin and fate of process-related impurities.

Process Hazards Testing

Alphora’s process hazards laboratory vets processes prior to scale-up for harmful or energetic reaction conditions; preventing personal injury, avoiding unexpected delays, and ensuring a viable clinical and commercial process.

 

Design of Experiments (DOE) and Quality by Design (QbD)

A variety of DOE approaches are utilized by Alphora to address challenging synthetic steps and in advance of commercialization. Our DOE tools include Modde™, JMP™, Design Expert™ , and DynoChem™ software; as well as Polyblock™ and MultiMax™ equipment. Alphora has validated a number of processes and also employs QbD approaches.

 

Continuous Flow Technology:​

Alphora employs two technology platforms for continuous flow: micro-chip based Labtrix™ and coil based Vapourtec™. This enabling technology is ideal for problematic syntheses and to address safety issues. A Kilotrix™ system is also available for cGMP scale-up.

 

Intellectual Property Enhancement

Our team also has considerable experience in generating new intellectual property and in its value enhancement for our client’s portfolios.

 

ANALYTICAL DEVELOPMENT | API and process understanding

From inception, Alphora has placed a significant emphasis on our Analytical investments, to support and guide process development for complex API processes. Our analytical laboratories are very well equipped with state-of-the-art technology. Our analytical chemists are experienced in tackling the most challenging problems and establishing controls for the synthetic process and ensuring API quality.

 

Our focus includes:

  • Method development

  • Method qualification and validation

  • In-Process-Controls

  • Characterization of regulatory starting materials, intermediates and API’s

  • Phase appropriate specifications

  • Solid state characterization

  • pGTI’s, impurities and related compounds

  • Extensive experience with non-Chromophore API’s and intermediates  

cGMP SCALE-UP 

 

cGMP Kilo Laboratories

Alphora operates multiple cGMP Kilo Laboratories to scale-up processes to the 50 litre scale for clinical and niche commercial API’s. These units are equipped with cryogenic, chromatography and hydrogenation capabilities.

 

cGMP Manufacturing Plant

Alphora operates a sophisticated cGMP Pilot Plant to the 500 litre scale to provide larger quantities of API for clinical and niche commercial requirements. The pilot plant is also equipped with cryogenic, chromatography and hydrogenation capabilities.

 

cGMP Chromatography

Alphora has invested in chromatography tools across the organization to support complex chemistry and the timely scale-up for early stage clinical API’s.

 

Our R&D Laboratories, Kilo Laboratories and Pilot Plant are all are equipped with Biotage™ systems for seemless technology transfer from the bench to plant.

 

Alphora also possesses high pressure preparatory LC capabilities for the laboratory and cGMP environments.

 

cGMP STABILITY TESTING

 

Alphora provides cGMP, ICH compliant stability studies to support regulatory CMC programs, and to support process development:

  • Conditions include: -80°C; -20°C; 5°C; 25°C/60%RH; 30°C/65%RH; 40°C/75%RH

  • ICH Photostability Testing Capability

  • Stability Studies: Raw materials, intermediates, API’s, and alternative salt and ploymorph forms

  • Stress studies, accelerated and long-term stability studies

 

QUALITY & REGULATORY 

Quality Assurance & Quality Control

Alphora has successfully been inspected by international regulatory agencies as well as our clients.

        ✓  FDA – 2008, 2011, 2014, 2016

        ✓  Health Canada – 2014, 2016

        ✓  Numerous domestic and international clients

The experienced quality team works with our clients to meet their phase appropriate quality and regulatory needs.

 

Regulatory

Alphora can assist clients with their regulatory filing; whether for preparation or review of CMC or DMF filings.

NICHE API EXPERTISE

Niche API’s

Alphora’s facility is ideally suited for the commercialization of niche API’s. Alphora has developed and validated several processes which are in approval with regulatory authorities.

 

High Potency Capabilities

Alphora is experienced with the development and handling of highly potent API's. Our Research & Development suite and separated cGMP scale-up facility can handle potent compounds to less than 30 ng/m   (Safebridge™ Class 4.)

3

 
 

PHASE APPROPRIATE DEVELOPMENT | Success at each stage

Alphora's talented process and analytical chemists provide phase appropriate solutions which consider the client's immediate needs as well as the longer term commercial requirements. At every stage, Alphora strives to provide the client with a development road map to provide the “Right Development at the Right Time”.

 

 

 

 

 

 

 

IND Enabling Development:

For early stage projects, where speed and quality are typically paramount:

  • Pre-clinical samples

  • Route development

       >  Process reliability and reproducibility

       > Process economies

       >  Regulatory strategies

       >  Reduction in Cost of Goods (COGS)

  • Synthetic & process chemistry

  • Analytical Method Development

  • Specification Development

  • Product Characterization

  • Analytical Method Qualification/Validation

  • non-GMP Scale-up

  • cGMP Scale-up

  • Early Stage Chromatography

  • Stress and accelerated stability studies

  • ICH Stability

  • IND document preparation & review (CMC or DMF preparation)

Phase II/III Development:

Alphora applies incremental development for phase II & III programs. These efforts include:

  • Process development and optimization

  • Analytical Development

  • Specification Development / Enhanced Control

  • Impurity identification and control

       >  Origin and Fate

       > Spike and Purge Studies

  • API characterization

  • Regulatory Starting Material (RSM) Sourcing Development

  • Technology Transfer for larger scale API’s

 

Phase II Process Re-development:

Alphora has re-developed a number of externally developed phase I processes for phase II; to address deficiencies in the route, process chemistry, economics, regulatory and analytical controls, while targeting existing impurity profiles to avoid bridging toxicity studies. The new process is typically demonstrated at the Kilo Laboratories or Pilot Plant scale and if required, technology transferred to a CMO facility.

 

Commercialization Development:

Alphora has conducted a number of process validations for commercial manufacturing of niche API’s. Our services include:

  • Critical Parameter studies

  • QbD approach

  • DOE studies

  • Preparation and execution of process validation protocols

  • Development and audit of supply chain

  • Stability of raw materials and intermediates

 

 

OUR DEVELOPMENT SERVICES

 

Alphora provides a comprehensive suite of phase appropriate solutions to ensure clients receive the “right development at the right time”.

 

These include:

  • Route development

  • Pre-clinical synthesis and samples

  • Process development and optimization

  • Analytical method and specification development

  • Analytical method validiation

  • Supply chain development for key raw materials and Intermediates

  • Phase II process re-development to address economic and regulatory requirements

  • Final isolations, purifications and physical characteristics

  • Product Characterization

  • Process impurities: isolation and synthesis; origin and fate; spike and purge

  • Design of experiments (DOE) investigations

  • Quality by design (QbD)

  • Non-GMP synthesis

  • cGMP synthesis

  • cGMP chromatography

  • Stability Studies

  • Process Validation

  • Commercial manufacturing for Niche API’s,
    and HPAPI’s 

  • DMF and CMC review or preparation