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From Bench to Clinic to MarketMay 2020
Table of Contents
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1 3
ResourcesWho we are
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Future DevelopmentsContract Development and
Manufacturing
Who are we?
LuinaBio is one of Australia’s most experienced
biopharmaceutical CDMO’s.
We offer two types of services:
• Strain and process development
• GMP manufacture of:
• Recombinant proteins & vaccines
• Live Biotherapeutics
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Why work with us?
• Over 20 years expertise in biopharmaceutical production from bacterial /
yeast cell lines
• Cell line development
• Process development
• GMP material for all clinical phases and market
• Experienced project management
• Highly cost competitive
• Extremely flexible with fast access and turnaround times
• Access R&D tax credit (43% upfront govt. rebate)
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Initial process flow
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Initial contact CDA RFP Proposal Evaluation Acceptance
Start of RM sourcing
Slot finalised
Invoicing
Project execution
Signature Evaluation Purchase Order Signature Evaluation MSA
Luina Bio Responsibility
Customer Responsibility
Continuing process flow
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Proposal Evaluation Acceptance
Signature Evaluation Purchase Order
Start of RM sourcing
Slot finalisedInvoicing
Project execution
Luina Bio Responsibility
Customer Responsibility
LuinaBio Experience
• Bacterial & Yeast Fermentation
• Live Biotherapeutics (Aerobic/Anaerobic; BSL1/BSL2)
• Recombinant proteins
• Carbohydrates and carbohydrate conjugates
• Vaccines and immunotherapies
• DNA/Gene therapies
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Track Record
LuinaBio provides services to global, multi-national and local
clients. Recent projects include:
• Recombinant protein from E.coli for a phase 3 trial in the US under IND
• Recombinant protein from E.coli conjugated to a carbohydrate for a
phase 2 in the US under IND and phase 2/3 trial in the EU;
• Over 10 strains strictly anaerobic LBP for phase 1 in the US under IND
• Whole cell killed vaccine for a phase 2 trial in the US and Australia
under IND.
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Cost comparison USA Australia
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100 72 44
USA
Australia
Australia ( with R&DTax)
Currency conversion rate AUD1 = USD 0.9Study By Frost and Sullivan 2016
Cost comparison for a standardized early phase trial conducted in Australia and USA
The savings for process development and manufacturing are comparable
Contract Manufacturing • Process Development
• Recombinant Proteins
• Live Biotherapeutics
• Vaccines
• Plasmid DNA
Process development
Luina Bio offers the following services to prepare your project for
successful cGMP Biomanufacturing
• Strain development
• Fermentation development
• Purification/recovery strategies
• Process validation
• QC assay development / validation
• GMP document preparation
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Case Study: Process development
• Luina Bio was approached to develop a method for the
manufacture of a recombinant protein for clinical use
Challenges
• Development of a suitably expressing E. coli strain. The host/vector
system is to be IP free.
• Development of fermentation conditions maximising yield resulted the
formation of inclusions bodies
• Development of a selective purification process minimising losses
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Luina Bio Solutions
• Selection of bacterial lines/plasmids that allows for ease of access,fermentation robustness and ease of mid-stream processing withfreedom to operate
• 5 plasmids trialled together with 2-3 host combinations
• Selection of induction system
• Selection of fermentation conditions adjusted to allow for the consistentand controlled expression of the native target protein into theperiplasmic space
• Purification was simplified following the presence of native protein inthe periplasmic space
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Case Study: Process Development
Outcome
• A new, rhamnose induced, highly performing plasmid/host
combination was created
• The optimal conditions for maximal native protein expression
were determined
• Purification efficiency was increased.
• The stage is set for simple and efficient cGMP biomanufacture
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Case Study: Process Development
Microbial Fermentation
Luina Bio offers the following services in microbial fermentation
for both bacterial and yeast strains:
• Master and working cell bank preparation, validation and storage
• Fermentation and subsequent downstream purification
• Downstream processing optimisation and development
• Up/downscale Fermentation
• Multiple feed strategies and media options
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Case Study: Novel recombinant protein
• Luina Bio was approached by a new client to manufacture a
recombinant protein designed in a novel expression system.
The client required the API for use in human clinical trials.
• Challenges
• A novel bacterial expression system not fitting within existing import or
OGTR licences.
• Expression only ever performed at small scale
• Atypical purification parameters
• Extremely low endotoxins specification on final API
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• Luina Bio Solutions
• Luina Bio was able to use internal skills to obtain necessary import and
OGTR licences.
• Luina Bio designed and implemented a successful scale-up program,
taking the final fermentation into our 600L fermenter.
• Luina Bio worked closely with the developers of the expression system
to refine and shorten the purification parameters, resulting in consistent
production.
• Luina Bio undertook an extensive risk assessment and process review
to eliminate the possibility of endotoxins contamination. A number of
facility enhancements were incorporated into the review.
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Case Study: Novel recombinant protein
• Outcome
• Luina Bio successfully introduced and upscaled the fermentation
process.
• Furthermore, increased refinement of the purification process resulted
in an approximately 50% increase in the overall product yield.
• The product was manufactured and released under cGMP.
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Case Study: Novel recombinant protein
Live Biotherapeutics
LuinaBio is highly experienced in working with aerobic to
strictly anaerobic strains:
• Aerobic/anaerobic cell bank preparation and qualification
• Aerobic/anaerobic fermentation up to 500L
• Aerobic/anaerobic mid stream and downstream processing
• Aerobic/anaerobic lyophilisation of live cultures
• Aerobic/anaerobic product packaging
• Entire process <100ppm O2 if needed
• BSL-1 /BSL-2
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Experience
• Bifidobacterium spp.
• Bacteroides spp.
• Dorea spp.
• Lactococcus spp.
• Eubacterium spp.
• Faecalibacterium spp.
• Bacillus spp.
• Odoribacter spp.
• Christianella spp
• Roseburia spp.
• Lactobacillus spp.
• Prevotella spp.
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Luina Bio has experience with the following bacterial genera:
Case Study: Live Biotherapeutic
Luina Bio was approached by a new client to manufacture a suite of
Live Biotherapeutic Products (LBPs) for use in a range of human
clinical trials.
Challenges
• New and novel bacteria not fitting within existing import permits
• Strict anaerobic control required to ensure organism viability
• Fermentation, harvesting, concentration and lyophilisation to be carried out
under strict anaerobic conditions
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Case Study: Live Biotherapeutic Luina Bio Solutions
• Use internal skills to obtain necessary import permits
• Installation of equipment to allow creation of anaerobic master cell banks
• Modification and requalification of large scale fermenters to create and
maintain strict anaerobic conditions
• Design and implementation of a cell concentration and harvest system that
could be sterilised in place and used while maintaining strict anaerobic
conditions
• Development and implementation of techniques to maintain strict
anaerobic conditions during lyophilisation and final dry product harvest and
sieving
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Outcome
Luina Bio successfully produced a suite of 10 lyophilised Live
Biotherapeutic Products that met or exceeded the clients’ viability
specifications.
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Case Study: Live Biotherapeutic
Vaccine Production
Luina Bio offers cGMP production of bacterial vaccines
• Production of recombinant vaccines
• Production of heat shock induced vaccines
• Production of live or killed bacterial vaccines
• Specialty in formalin killing and removal
• Human and animal health vaccines
• Documentation
• Support services
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Case Study: Vaccine Production
• Luina Bio was approached to produce vaccines effective
against meningococcal ACWY strains and Haemophilus
influenza, for use in human clinical trials
Challenges• Vaccine production potentially exposed manufacturing scientists to the infectious
agents that the vaccines are designed to protect against
• Complex mixtures of proteins are produced and ratios need to be maintained
during production
• Analytical techniques are required to identify and quantify the active components
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Luina Bio Solutions
• Luina Bio conducted an extensive risk assessment on the process and
implemented all recommendations to ensure operator safety, including
using operating procedures designed to provide higher than BSL2
protection within our PC2 Large Scale facility
• Fermentation and purification parameters were closely monitored to
ensure no deviations from the required process
• Luina Bio prepared and executed analytical validation protocols to
ensure analytical techniques were suitable
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Case Study: Vaccine Production
Outcome
• Luina Bio successfully manufactured the vaccines to meet client
specifications and timeline
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Case Study: Vaccine Production
Plasmid Production
Luina Bio offers cGMP production of plasmid DNA for transfection
of mammalian cells.
• Master and working cell bank preparation, validation and storage
• Fermentation and subsequent downstream purification
• Downstream processing optimisation and development
• Up/downscale Fermentation
• Multiple feed strategies and media options
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Case Study: Plasmid Production
Luina Bio was approached to produce Plasmid DNA in GMP by
an Australian biotechnology company
Challenges
• Complexity of growing the transformed bacterial cell line
• Challenging purification procedures had to be transferred and
perfected to ensure a useable product was obtained
• Analytical transfer and management of analytical suppliers
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Luina Bio Solutions
• A process was developed for maximal expression of the plasmid
• Fermentation and purification parameters were closely monitored to
ensure no deviations from the required process
• Purification processes were developed to ensure repeatability of
process
• Luina Bio prepared and executed analytical validation protocols to
ensure analytical techniques were suitable
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Case Study: Plasmid Production
Outcome
• Luina Bio successfully manufactured the plasmid to meet client
budget, specifications and timeline
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Case Study: Plasmid Production
Facilities
LuinaBio's 1,200m2 facility is located in Brisbane,
Australia
• It comprises of a series of modular clean room laboratories with
ISO 8 fermentation suites and support areas.
• Purification and final product isolation suites are ISO 7 clean
rooms.
• The laboratory area is supported by a range of raw material, in-
process and finished product storage areas ranging from -80°C to
controlled ambient.
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Processes and Equipment
• Fermentation at 5L, 30L, 75L and 500L scale
• Fed batch capabilities
• Cell recovery
• discrete centrifugation
• continuous centrifugation
• ultrafiltration
• Microfluidics and Niro Soavi high pressure homogenizers for cell rupture
• Final product filtration
• Lyophilisation
• bulk (up to 40L)
• vials
• stoppering
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• Chromatography
• AKTA 100 system (100mL/min)
• AKTA Biopilot (800mL/min)
• AKTA Bioprocess skid (2,000mL/min)
• AKTA Ready single-use Bioprocess skid (6,000mL/min)
• Chromatography columns 2L to 200L
• Independent Cell Culture Suites
• State-of-the-Art Testing Laboratories – with a full array of testing capabilities
• cGMP Compliant Warehousing – for raw materials and formulated bulk product
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Processes and Equipment
Facility Licenses
LuinaBio has the following operating licenses:
• TGA (Australian FDA equivalent) license for the
manufacture of human therapeutic API's from
biological and synthetic sources
• APVMA (Veterinary equivalent of the TGA) license for
manufacture of sterile immunobiological products
• OGTR license for the production of products from
genetically modified organisms
• DAF (formerly AQIS) facility license for import and use
of biologic materials
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Quality Management
LuinaBio invests heavily in Quality Management• We operate under and comply with the PIC/S GMP code
• Audited and certified by the TGA in November 2018
• Audited by clients including the Pfizer and Zoetis global audit teams
• Audited to USFDA requirements by independent consultants
• We expect and welcome your audit
• More information on our quality systems is available
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Future developmentProcess Development Aseptic Fill Finish
Microbiome production
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Process Development
Luina Bio will enhance its process development capability by creating a new
laboratory in Brisbane.
• The first phase of the laboratory expansion is currently operational and
allows our scientists to work on early upstream and downstream
development, scale up and analytical work.
• The second phase will start soon and will allow us to expand our parallel
fermentation capability and bring our scale up capacity to 500L.
This will allow us to be faster and more responsive to our customers
development needs.
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Aseptic Fill Finish
Luina Bio has started work on building an aseptic fill finish plant in Darra, QLD.
The plant will be able to aseptically fill bottles, vials and syringes (0.5 to10ml) in cGMP with
runs up to 5,000 units. The plant will be entirely based on single use materials to ensure
compliance and rapid access
The core of the work in this facility is expected to come from companies looking for Phase 1
and 2 aseptic fill-finish independently from the nature of their API.
Expect start date Q4 2021
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GMP Manufacturing
Luina Bio has started planning for the establishment of a greenfield site commercial live
microbial biotherapeutic product manufacturing plant for the pharmaceutical industry.
This plant will have a number of medium to large scale fermenters in parallel each with its
own dedicated purification and freeze drying train. All trains will be able to work in strictly
anaerobic conditions if needed.
This will allow our customers to have faster production of multiple strains as a number of
strains will be fermented concurrently.
Expected Start date Q4 2021
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Thank youMax Rossetto, General Manager, Business Development
E: [email protected] T: +61 400 987 334
Supporting you
From Bench to Clinic to Market
