Biomanufacturing Services / Contract Manufacturing Biopharmaceuticals

1. Therapure Biopharma Inc
BIOPROCESSING SERVICES
www.therapurebio.com
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2. CONTENT
Overview
Quality Charter
Technology Transfer Services
Process Development Services
Testing and Laboratory Services
Validation Services
Manufacturing Services
Manufacturing Facility
Warehousing and Distribution
Project Management Services
Why Choose Therapure Biopharma?
www.therapurebio.com
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3. OVERVIEW
Our customers understand that today’s regulatory requirements are increasingly difficult to
meet while cGMP manufacturing processes are becoming more complex. The odds of
successfully bringing a product from preclinical through clinical to commercial success are
less than 1:100 in today’s regulatory and economic environment. The ability to quickly
respond to these requirements, as companies strive to bring their products to market, can be
found at Therapure Biopharma. Let us help you succeed by by improving the odds.
Therapure Biopharma not only has the expertise in the documentation, testing and control of
manufacturing for biological parenteral products but the experience, flexibility and capability
to deliver your product.
Therapure Biopharma, located in
Mississauga, Ontario, Canada, is
an integrated biopharmaceutical
manufacturing company with
comprehensive experience in the
development and manufacture of
innovative life sustaining
therapies. Our business is to
serve the outsourcing needs of
the biotechnology industry.
Leveraging our many years of
professional expertise, we can
bring our clients’ products to
market quickly and cost
effectively while ensuring quality
and confidentiality.
We have the technical expertise, quality systems and modern and flexible facilities to develop
and manufacture your product, allowing you to focus on your goal - achieving market
approval.
As acknowledged experts in the purification of proteins from a biological source we offer
cGMP manufacturing, development and testing of large and small volume parenterals,
biologics and protein therapeutics to satisfy, U.S., European and Canadian regulatory
requirements. We have developed processing systems capable of handling the purification of
up to 100 kg of protein per batch. Our quality program is designed to ensure all aspects of
manufacturing, testing, storage, and delivery of your product are documented and procedures
are in place for regulatory compliance.
www.therapurebio.com
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4. OVERVIEW
Therapure Biopharma’s flexible approach to bioprocessing allows us to tailor our services to
our client’s specific requirements. We can perform selected activities or serve as a single
source – from product development through to commercial manufacturing. Our experience
combined with our capabilities in design, technology, validation and regulatory support help
ensure your product will move unimpeded through the manufacturing process and allow you to
focus on your goal of obtaining market approval.
Commercial Manufacture (cGMP)
Clinical Manufacture (cGMP)
Pre-Clinical Manufacture
Contract Testing
Commercial
Test Method Development Success
Process Development
Optimization
Scale-Up
From pre-clinical to commercial bioprocessing including process development, scale-up and
optimization, testing and test method development, purification and aseptic filling, Therapure
Biopharma can deliver your requirements.
www.therapurebio.com
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5. QUALITY CHARTER
Therapure believes in the principle that quality must be built into a process or product and
not tested in. This not only applies to the compliance and regulatory requirements but to
the way we treat our clients and run our business. To this end we put Quality first in all
aspects as highlighted in the Therapure Quality Charter provided below.
Our vision
•A Worldwide leader in protein purification and related biotechnology fields.
•Provide services for all phases of the protein purification lifecycle, from bench to market.
•Enhance our expertise in advanced biology, complex proteins and regulatory processes
to develop effective and innovative solutions for our clients.
•To seek long-lasting relationships with our partners/clients by providing product and
services, which exceed their expectations.
Our mission
•Therapure Biopharma Inc. is a Canadian biopharmaceutical company committed to the
development, manufacture, purification and packaging of high-quality biological
therapeutics.
Our value
•Understanding our clients needs to ensure customer satisfaction.
•Providing expertise, know-how and capability to address client issues.
•Professional ethics, principles and adherence to quality beyond the standard.
•We can be trusted.
•We live the Therapure Quality charter.
Our Quality Policy
•To consistently exceed all worldwide regulatory requirements.
•Live the theme of ‘prevention over correction’ approach. The goal is ‘upstream quality
control’ (i.e. “doing it right the first time”) by designing processes to be as error free as
possible, within cost/risk constraints.
•Promote continuous improvement in all fields of activity through precisely defined goals,
measurable indicators and an integrated Quality Management system.
•Building and using internal and external customer-supplier relationships to define,
measure and improve quality.
•Open communication, both internal and external, is the key to ensuring quality in all
aspects.
•To maintain our skills at the forefront of technology.
www.therapurebio.com
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6. TECHNOLOGY TRANSFER SERVICES
A key step to achieving commercial success is
understanding the manufacturing process. The
technology transfer process defines and evaluates an
existing process to allow for scale-up, site transfers or
process modifications. Technology transfer is vital to
ensuring an optimal process that is both efficient and
cost effective. Defining a viable commercial process for
a biopharmaceutical product is paramount to that
product's success. Prior to cGMP production, the
process should be well understood, robust, scalable and
documented. While this can be challenging, this step is
crucial for the development of a well defined process for
biopharmaceutical manufacturing.
The technology transfer process is unique for each
project; however there are standard activities which
must take place.
1. The development of a comprehensive scope of work is essential to the success of
the project. This will define, in detail, the work to be performed, deliverables,
milestones and scheduling. The responsibilities of both parties will also be
delineated and the change control process approved.
2. Due Diligence involves the detailed transfer of information to the new manufacturing
site. This includes all existing process and formulation documents, raw material
requirements, testing specifications, standard operating procedures, equipment
requirements, regulatory commitments and quality specifications. This step is
essential to form a basis for manufacturing and testing in compliance with cGMP
and CMC commitments to ensure product integrity, quality and purity.
3. Verification Batches will be run once the set up and installation of all manufacturing
process steps and in-process analytical methods is achieved. These verification
batches will be produced at the existing scale to demonstrate successful transfer of
the current manufacturing process. They will also establish a baseline for product
yields and recoveries as well as identifying potential scale-up issues.
4. Qualification Batches verify that the biopharmaceutical product can be consistently
and reproducibly manufactured to specifications and executed at scale. Draft Batch
Production Records and Standard Operating Procedures will also be prepared
according to cGMP guidelines.
www.therapurebio.com
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7. TECHNOLOGY TRANSFER SERVICES
The result of a successful technology transfer is an executable cGMP process with the
quality systems in place for commercial manufacturing.
Therapure Biopharma has the knowledge and skill sets to move a product from bench-top
through clinical and greater scale. Our team has the experience to evaluate processes,
determine scale-up and optimization requirements and document the processes required to
fulfil regulatory requirements.
www.therapurebio.com
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8. PROCESS DEVELOPMENT SERVICES
Therapure Biopharma understands the sensitivities, complexities and potential limitations in
bringing a product to market. Determining the most efficient and cost effective manufacturing
methods as early as possible in the process is essential. At the same time, using cGMP
methodologies for scale up and optimization reduces or eliminates the need to recreate clinical
trials.
Our goal is to devise a process for cGMP manufacturing that establishes procedures to
minimize manufacturing downtime, streamline scale-up and maximize product yield and purity.
Our extensive knowledge in protein based processes allows us to examine current procedures
and techniques and determine the most comprehensive plan of action to ensure manufacturing
success.
Therapure Biopharma’s process development and engineering teams have taken
biopharmaceutical methods developed in the lab, generating milligram quantities of
protein/product, and successfully transferred them from pilot scale through to commercial level
operations designed to produce up to 7,500 kilograms of protein/product per year.
The team includes engineers, Master’s and Ph.D level scientists experienced in protein,
carbohydrate, lipid and nucleotide chemistry and their associated analytical tools. Our team
has expertise in many areas including:
• Filtration;
• Cell separation;
• Viral inactivation;
• Oxygen sensitive products;
• Chromatography;
• Protein modification;
• Aldehyde reaction chemistries;
• Cross-linking technologies;
• TFF/crossflow filtration;
• Centrifugation;
• Aseptic and sterile filling;
• Cell culture services; and
• Mammalian cell fermentation.
Our knowledge includes design, scale-up/scale-down and validation of viral clearance
technologies. Our expertise in working with oxygen sensitive materials stems from our
hemoglobin experience. Reaction kinetics and yields can be optimized through our extensive
chemical and biochemical knowledge.
We are committed to maximizing yield while minimizing cost, maintaining product purity,
process robustness and satisfying cGMP requirements.
www.therapurebio.com
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9. TESTING AND LABORATORY SERVICES
Quality control is key to the successful development, transfer and subsequent manufacturing
of any product. Therapure Biopharma’s Quality Control team provides a broad range of
services to ensure our clients’ product meets all necessary conformance standards. Our
established quality program is designed to fulfil requirements set by regulatory authorities and
is continually being updated to ensure cGMP compliance. We have a diverse range of skills in
several areas including large and small volume parenterals, biologics, blood products, aseptic
and sterile processing.
To ensure reliable results, Therapure Biopharma’s established quality assurance program
includes systems for control of documentation, test samples, reagents and standards, test
methodology, test instruments, failure investigations and method validation.
CONTRACT TESTING
Therapure Biopharma has 12,500 square feet of
laboratories for research and development, in-
process and finished product testing, analytical
and microbiological testing and stability studies.
We have the laboratory control systems and
equipment in place to accommodate cGMP test
requirements.
In addition to the Quality Control tests provided by
Therapure Biopharma, we have agreements with
qualified off-site facilities to perform custom
testing.
STABILITY STUDIES
Therapure Biopharma has a broad range of stability programs and services including:
• Stability program design;
• Preparation of protocols and reports;
• Controlled stability sample storage;
• Stability testing; and
• Stability data statistical analysis.
Custom stability programs can be designed and executed for raw material, process intermediate
and final product shelf-life determination.
www.therapurebio.com
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10. TESTING AND LABORATORY SERVICES
METHOD DEVELOPMENT
As important as the process development of a product is the development of the test methods
for measurement of purity, activity and potency as well as other product specifications.
Therapure Biopharma has extensive knowledge in the test method development for products
of biological origin.
In order to document your test method procedures we:
• Research current literature;
• Evaluate sample matrices;
• Identify appropriate characterization methods (chromatography, spectroscopy);
• Design and optimize analytical methods (column types, flow rates, sample preparation,
etc.) including evaluation for robustness;
• Provide a preliminary evaluation of precision, accuracy, specificity, etc.;
• Develop test system suitability controls; and
• Establish a test development record for our clients’ use and filing.
We establish scientifically sound test procedures to assure the conformance of your product to
the appropriate standards of identity, strength, quality and purity.
www.therapurebio.com
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11. LABORATORIES
Therapure Biopharma has 12,500 square feet of laboratories for research and development,
in-process and finished product, analytical and microbiological testing and stability studies.
Designed to meet our clients’ requirements the Raw Materials, Analytical Chemistry and
Microbiology Laboratories operate in compliance with cGMP requirements and can handle
testing of a wide variety of chemical and biological agents. Therapure Biopharma performs
tests using fully qualified laboratory instruments and ensures continued control by performing
routine calibration, maintenance and demonstration of system suitability.
• Raw Materials
o Raw Material control, sampling, ID and
purity testing and reserve sample storage in
compliance with regulatory guidelines
o Establishment of Raw Materials
Specifications, Raw Materials Qualification
and Supplier Quality Monitoring.
• Analytical Chemistry
o Services a variety of needs for protein and chemical analyses including identification
testing, purity assessments, quantitation of impurities and contaminants,
characterization and measurements of biological activity
www.therapurebio.com
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12. LABORATORIES
• Microbiology
o Utilizes fully validated Isolator technology to perform microbiological testing
including sterility testing, bacteriostasis/fungistatis, bioburden, bacterial endotoxin
(LAL), particulates and environmental monitoring
• Research
o There is 5,700 square feet of Research laboratories available to provide support for
Product Development and Quality Control activities
Large fume hoods and lab bench exhaust vents allow work with potentially hazardous
chemicals. Freezers, refrigerators and incubators are temperature and humidity controlled
and monitored to address most sample/material storage conditions. The laboratories house
controlled and monitored stability storage chambers capable of meeting ICH temperature
and humidity requirements with a temperature range of -80° to +70°C and humidity range of
55 to 100% RH. Validated Isolator technology is used to perform microbiological testing.
www.therapurebio.com
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13. VALIDATION SERVICES
Validation is essential in demonstrating that tests and processes developed for a product are
robust and under control. Therapure Biopharma, as a cGMP manufacturer, is committed to
using the principals of validation to ensure that a specific process will consistently produce a
product meeting pre-determined specifications and quality attributes.
TEST METHOD VALIDATION
One of the most important steps before filing a marketing application is the early validation of
analytical test methods used to determine the potency, purity, identity, quality, safety and
stability of a drug and its intermediates.
Analytical method validation is typically an ongoing process in parallel with product
development. Therapure Biopharma has the capability to perform full test method validation
in accordance with the current ICH guidelines. Therapure Biopharma’s Quality system
requires that test methods have a written and approved test procedure and a trained operator
prior to initiation of validation. Method validations are executed according to an approved
validation protocol. The validation plan ensures that there is documented evidence of
suitability including accuracy, precision, sensitivity (LOD, LOQ), specificity, linearity and
range.
PROCESS VALIDATION
Our validation expertise extends to Process/Performance Qualification (PQ) of many typical
biopharmaceutical operations such as:
• Viral clearance
• Filtration/clarification
• Purification
• Aseptic filling
• Scale-up operations
www.therapurebio.com
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14. VALIDATION SERVICES
Therapure Biopharma has extensive experience in the writing and execution of Installation
and Operational Qualification (IQ/OQ) protocols for a broad range of systems including:
• GMP utilities
• Clean In Place (CIP) & Clean Out of Place (COP) skids
• Cold rooms
• Steam in Place (SIP)
• Incubators
• Solution Preparation
• Autoclaves
• Filtration
• Chromatography
• Filling systems
We also possess the in-depth knowledge and the ability to address process cleaning
validation requirements.
www.therapurebio.com
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15. MANUFACTURING SERVICES
Therapure Biopharma’s manufacturing capabilities extend from the laboratory bench-top to
large-scale commercial production. We have the ability to provide protein purification and
aseptic processing at any scale and to produce sterile injectable protein solutions.
Designed for flexible operation, Therapure Biopharma’s modern manufacturing and testing
facility meets or exceeds the existing standards of the FDA (U.S.), HPFB (Canada), EMEC
(Europe) and MCA (U.K.). The facility has over 26,000 square feet of clean space. The clean
room manufacturing areas are organized into pressurized zones, meeting cGMP requirements.
The facility is designed and serviced to accommodate modular equipment. Strategic
placement and use of removable clean room panels, roll-up doors and removable exterior
walls allows the creation of custom areas and facilitates easy installation and removal of
processing equipment. Manufacturing suites range from Class 100,000 and 10,000
downstream processing areas to Class 100 filling areas. Explosion rated rooms are equipped
with blow-out panels which are suitable for operations involving solvents and/or flammable
material. Containment areas are under negative pressure to allow processing of items such as
biohazardous materials.
The facility is readily adaptable to manufacture bio/pharmaceutical products that satisfy pre-
clinical, clinical or commercial requirements.
• Chromatography capabilities with columns sizes
ranging from 0.4 cm to 1 meter in diameter;
• Equipped to handle both biohazardous and
flammable solutions in dedicated suites;
• Normal flow filtration equipment ranges from
disposable capsules to stainless steel housings
capable of holding eighteen 30quot; filters;
• Extensive tangential flow filtration (TFF)
capabilities range from stir cells and 'slice' holders
on the bench top scale to dedicated TFF skids
with membrane areas up to 80 m2;
• Solutions preparation capabilities extend from
small volumes using standardized laboratory
glassware through to a 6000-L stainless steel
mixing tank; and
• Stainless steel process tanks range in size from
10 L to 3000 L allowing for a wide range of
processing possibilities.
Therapure Biopharma is fully equipped to perform sterile filling operations into IV transfusion
bags using a semi-automated filling machine or into bottles or vials in the dedicated fill suite.
www.therapurebio.com
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16. MANUFACTURING FACILITY
Therapure Biopharma’s 130,000 square feet manufacturing and testing facility is conveniently
located in the heart of the biopharmaceutical area in Mississauga, Ontario (part of the Greater
Toronto Area). The building is just minutes from Lester B. Pearson International Airport –
Canada’s largest airport and borders on two of Canada’s major highways.
The facility incorporates the Raw Materials, Analytical Chemistry, Microbiology and Research
Laboratories, as well as clean room manufacturing areas and warehouse storage.
Mechanical Base Utilities
Penthouse
Process
Clean Rooms
Explosion Clean Utilities
Rated Room & Buffers
Central Service Chase
The building was specifically designed to allow flexibility of use with a variety of features that
are ideal for bioprocess manufacturing.
Therapure Biopharma’s multiple HVAC systems allow for segregation of process areas, positive
and negative pressurization schemes and areas where no recirculation/mixing of air is allowed.
Selected suites are configured under negative pressure for containment of biologic materials
prior to pathogen removal/inactivation steps, preventing cross contamination to subsequent
downstream purification areas. The system also utilizes terminal HEPA-filters dedicated to
various production areas meeting specific requirements for air cleanliness.
The facility has large capacity grey utilities available including chilled water, plant steam and
compressed air. The clean utilities include USP water, WFI, clean steam, CIP, process air and
medical gases. These utilities are distributed through a central service chase, which provides
all utilities to any production suite or process unit. This central service chase also allows for
independent utility changes, significantly reducing down time in the clean rooms and provides
adaptability for routing of process piping. A bulk solvent storage and delivery area and bulk
liquid nitrogen and oxygen gas storage facility have also been integrated into the building.
Waste treatment, Clean-In-Place (CIP) systems, buffer and solution preparation and water
purification systems are housed in the basement away from the main process areas.
www.therapurebio.com
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17. MANUFACTURING FACILITY –
STERILE FILLING CAPABILITIES
Aseptic Fill Capabilities
Therapure has aseptic filling capability in the formulation
and filling of sterile liquids into glass vials or preformed IV
infusion bags.
Aseptic vial filling suite includes:
• Vial wash
• De-pyrogenation
• Autoclaving
• Filling
• Dedicated HVAC
• Inspection
• Packaging
• range of fill volumes include 2ml to 200ml glass
vials, with rubber stoppers and capping.
• batch sizes (based on a single shift) range from
35,000 for the 2ml size, to 12000 for the 50ml and
3000 for the 200ml size
Sterile Preformed Bag Filling
• Preformed sterile bags and are aseptically filled
using a robotic filler and sealer that is manually
fed
• Secondary packaging
• bags can range from 50ml-1000ml
• up to 800 bags/hour
Lyophilization Services
• Development on line by Q2, 2009
• Commercial vial and bulk on line Q3, 2009
www.therapurebio.com
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18. WAREHOUSING
One of the challenges facing any successful company is the need to properly store and ship
finished product. Therapure Biopharma’s cGMP compliant warehouse and distribution service
can provide specialized product handling and tracking.
Warehousing
Therapure Biopharma’s 28,000 sq. ft. warehouse and distribution area is fully secured and can
be segregated to meet each client’s requirements. The monitored and secure warehouse is
capable of holding up to 544 composite plastic pallet positions that can be expanded to ~900
pallet positions of high density storage. Therapure Biopharma elected to use the composite
pallets to ensure that there is no contamination transferred from the wooden shipping pallet into
the warehouse or other process areas.
Segregated shipping and receiving docks
ensure full control of all materials entering or
leaving the facility.
We have an established and controlled raw
material system. The materials department
inspects all shipments to ensure correctness
and to check for damage. All items received
are input into our inventory control system
and given a unique number for traceability.
Raw materials are segregated and labeled
“quarantine” until being processed under
Therapure Biopharma’s raw material
approval procedure.
cGxP Storage
Spacious storage is available for raw materials and finished product. We offer a broad range
of storage conditions, temperature, humidity controlled and monitored including:
• 18,000 sq. ft. of warehouse space for • Incubators covering a range of
room temperature raw material storage; temperatures from 25° to 70° C;
• Freezer storage ranging from -85° to - • Explosion rated rooms for the
20°C; storage of hazardous raw
• Walk-in cold rooms ( 2° to 8°C) for the materials; and
storage of both raw materials and • Ambient storage.
manufactured product;
www.therapurebio.com
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19. WAREHOUSING
Distribution
Therapure Biopharma’s distribution services make certain your product gets to you when you
need it. Our shipping protocols are efficient and effective - we have successfully established
next day delivery throughout North America.
Tracking and look back procedures are established specifically for the quick traceability of
raw material usage
Shipping protocols, validated through several trial programs, ensure temperature and time
sensitive materials retain their integrity even during transit. We have alliances with numerous
carriers throughout North America and Europe familiar with these specialized requirements.
In addition, our established relationships with customs brokers have made the International
border between Canada and the United States appear invisible when dealing with shipments
of approved IND products.
We are familiar with the specific packaging required for protein derived products and will work
with you to ship your product in the shipping containers most applicable to your needs.
www.therapurebio.com
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20. PROJECT MANAGEMENT SERVICES
Successful management of every project is a priority for Therapure Biopharma. Our objective
is to ensure we fulfil our clients’ needs and expectations and that all parties are positioned for
success. Through our project teams we build solid, ongoing communications and joint
ownership of the process – from development to manufacture. We enable strong partnerships
between our clients’ and ourselves. A well managed project means there are no surprises –
for anyone.
The key to any successful project is ongoing communications between the parties. Thus, each
project is assigned an experienced project manager to manage the relationship between our
client and ourselves. Through ongoing interaction exceptional service is achieved. The project
manager is responsible for:
• Managing the project plan
• Chairing meetings
• Overseeing internal teams
• Preparing reports and reviews
• Managing the change control process
Timing represents one of the most critical elements in any project. Therapure Biopharma’s
project management teams ensure our clients’ product is delivered on time and on budget.
Our clients are integral participants in the planning process. A schedule will be developed
jointly and managed by the project team. Through the use of comprehensive Gantt charts all
project deliverables and tasks are tracked and monitored to achieve our clients’ goals.
If changes to the project are required, Therapure Biopharma’s change control procedure allows
for the flexibility necessary in today’s biopharmaceutical environment while maintaining visibility
of the impact on costs and timelines. Through the vigilant monitoring of project changes
successful project execution can be achieved.
Through proper management we ensure our clients’ expectations and requirements are met.
www.therapurebio.com
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21. WHY CHOOSE THERAPURE BIOPHARMA?
Therapure Biopharma’s unique and flexible features allow Therapure to attract local and
international partnerships with companies that require protein production and processing
services:
● Scale of production – capable of producing metric tonnes of protein annually;
● Range of production covered, from manufacturing to purification, to testing, formulation
and packaging;
● Flexibility of equipment and facility to accommodate a wide range of processes
sequentially and simultaneously;
● Scientific, manufacturing and regulatory expertise.
We can provide our customers with custom testing and technical advice including:
● Initial product characterization;
● Establishment of product specifications;
● Stability studies; and
● Product release programs.
Our manufacturing expertise can ensure rationale process design early in the process to avoid
expensive changes.
Our laboratories can establish proof in principle for your product design.
We can conduct feasibility studies to help work out difficult steps.
We can ensure that regulatory requirements are incorporated early to guarantee compliance
later. We also support our customers in the preparation of the required documentation for
regulatory submissions.
At all times we can provide guidance to ensure GLP/GMP compliance.
Please call us at +1 905-286-6200 or email to info@thereapurebio.com to discuss your
specific requirements and learn more about how Therapure Biopharma can assist you to bring
your product to market.
www.therapurebio.com
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