Thursday, December 30, 2010

Technology Transfer And Process Development

You have spent years in the laboratory developing a promising therapeutic protein that not only has tremendous market potential for your company but also global value in terms of the treatment of an unmet medical need. It has now come to that critical point in the program where you must choose a CDMO to take your therapeutic protein to the next level. But to whom can you turn with your valuable product? Who will take your therapeutic protein to that next level while respecting your requirements and continuing to involve you in the development process? Therapure is your trusted partner for efficient technology transfer and developing your manufacturing processes.

Therapure understands the time and effort invested into your drug candidate.

It is our goal to learn from your experience through our comprehensive Technology Transfer program that is designed to quickly and effectively transfer materials and to convey critical product knowledge from your team to ours. Through the creation of a joint Technical Project Team, we are able to effectively steer the development and manufacturing program ensuring your milestones are met.

Following project kick-off, Therapure’s extensive development experience comes to bear as your project is transferred to our labs.

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Therapure can provide a variety of product and process development services including the creation of a stable cell line or the optimization and scale up of your existing manufacturing process.

Therapure has the experience and service offerings for process development and optimization


Molecular biology :-

  • Vector design and construction
  • Host cell line transfection, amplification and selection
Cell banking (RCB, MCB, WCB)

Upstream cell culture development :-
  • Media selection and screening
  • Pre-culture optimization
  • Cell density and product expression optimization
  • 5L to 50L lab-scale cell culture capability
Midstream harvest development :-
  • Filtration (NFF, TFF)
  • Centrifugation
Downstream process development :-
  • Resin screening, selection and initial scouting
  • Chromatography column optimization and scale up
  • Tangential Flow Filtration (TFF) operations
  • Protein characterization
  • Viral inactivation/removal procedures
Product & buffer formulation development :-
  • Buffer composition development and stability testing
  • Lyophilization cycle development and optimization
  • Bulk and final product stability testing
Analytical method development :-
  • In-process and release testing

Wednesday, December 29, 2010

Pharmaceutical Support Services

Therapure operates under the principle, "Start with us, stay with us," meaning that we provide a range of support services to our clients minimizing logistics and creating one point of contact.

The following is a summary of our support services :-

Warehousing & Material Handling :-


Therapure operates a GMP-compliant 18,000 ft2 warehouse which includes :-
  • 24/7 access control and monitoring
  • Ambient storage for raw materials, consumables and final product
  • Freezer, walk-in cold rooms and incubator storage
  • Explosion-rated rooms for hazardous raw material storage
Distribution :-

To ensure finished goods arrive when and where they are needed, Therapure has established and validated shipping protocols with leading carriers for both cold and frozen products. Utilizing these protocols we are able to provide next-day deliveries throughout North America and Europe, both for clinical trials and regular commercial service.

Validation Support :-


Therapure provides a range of validation services including :-
  • Equipment
  • Cleaning procedures
  • Analytical Methods
  • Processes
  • Vendor Qualification
Stability Testing :-

Therapure works closely with each of our clients to develop a comprehensive bulk or final product stability program compliant with ICH guidelines.

By Therapure Biopharma :- A Protein Manufacturing and cGMP Contract Manufacturing Organization

Sunday, December 26, 2010

International Malaria Research Consortium Combines Technologies and Expertise From Two Continents to Tackle Deadly Disease

Research teams from three academic institutions and two private sector companies on two continents have come together to form the “International Malaria Research Consortium for the development of novel classes of antimalarials", (the "Consortium") a bold initiative to develop novel classes of drugs against malaria, a deadly disease in desperate need of new treatments.

Each of the Consortium's five partners brings unique capabilities spanning the spectrum from academic research to commercial development, and significantly - their existing technologies to the table. Through an extensive program design process, the parties hit upon unique combinations of these existing technologies that, combined with new drugs to be developed under the program, represent entirely new approaches to treating and potentially even eradicating this disease.

"It was a fascinating process to see different organizations with deep knowledge in their individual fields coming together and combining this knowledge to create innovative new approaches to the treatment of this disease" – Prof. Virander Chauhan, Director, International Center for Genetic Engineering and Biotechnology - New Delhi

"Creative leverage" is a term that comes to mind in describing this program. In addition to developing new therapeutics, we are also bringing together existing technologies developed by the partners and combining them in new ways such that one will have the potential to boost the effectiveness of another." - Dr. Lakshmi P. Kotra, Director, Center for Molecular Design and Preformulations, University Health Network and University of Toronto.

In a field that has seen very few new drugs introduced in the past 30 years, and where most of these drugs have lost effectiveness due to the emergence of drug resistant malaria strains, this program endeavors to develop entirely new classes of drugs, and furthermore will seek to develop drugs that, by their design, will hinder the emergence of drug resistance.

With funding from the International Science and Technology Partnerships Canada Inc. (ISTPCanada) and the Department of Biotechnology (DBT) of the Government of India, these new therapies will be developed and refined. Led by the site directors of each partner, Lakshmi Kotra at University Health Network/University of Toronto (Consortium lead in Canada), David Bell at Therapure Biopharma a (Biotech Manufacturing Inc) , Jitendra Verma at Lifecare Innovations, Asif Mohammed at the International Center for Genetic Engineering and Biotechnology (Consortium lead in India), and R. Mahesh at Birla Institute of Technology and Science, this program brings together a dynamic and talented groups of world-class scientists for a common cause of advancing basic research discoveries to preclinical development. This consortium brings their combined drug development expertise to the discovery and development of new compounds against targets in the parasite that causes malaria.

Current projects include the development of drugs against three malaria targets that the academic groups have researched extensively. This research is combined with the state-of-the-art tools and expertise in computer modeling, medicinal chemistry, nanoformulations and drug conjugation technologies from the consortium partners to advance potential drugs into IND enabling studies. The consortium has already made excellent progress since its activities started in April, 2010 and looking to expand the scope of the efforts with additional partners to advance the mission to develop clinically viable new antimalarials.

One example of this technology combination process is embodied in an objective to treat a form of malaria that resides in the liver. This form of the disease can re-emerge months or years after the initial infection to cause new illnesses in that individual. Additionally this form of the disease can re-introduce malaria into local populations where it had previously been eliminated - frustrating permanent eradication efforts. To tackle this problem the program will combine new drugs developed with existing technologies designed to deliver drugs to the liver in an effective form.

Other technology harnessed under the program will allow antimalarial drugs to be released slowly over long periods of time. This slow release gives the potential for a "one pill cure", a long sought after goal in anti-malarial drug development programs as it would allow the most effective utilization of often limited medical resources.

Malaria is one of humanities most devastating illnesses with an estimated 247 million cases worldwide in 2008 and almost one million deaths, mostly among children. In Africa a child dies every 45 seconds of Malaria and the disease accounts for 20% of all childhood deaths. Furthermore drug resistance is steadily undermining the effectiveness of existing treatments - driving the need for new therapies.

About Therapure Biopharma :-


Therapure Biopharma Inc. is an integrated biopharmaceutical company that develops, manufactures, purifies, and packages therapeutic Protein Characterization. Therapure Biopharma is also a specialist in therapies derived from hemoglobin, a blood protein. As a Pharmaceutical Contract Manufacturers Therapure Biopharma applies scientific, manufacturing, and downstream Purification of Protein expertise with an intimate understanding of advanced biology, complex proteins, and regulatory processes to develop effective and innovative solutions to advance products from discovery to market.

About University Health Network :-


University Health Network consists of Toronto General, Toronto Western and Princess Margaret Hospitals. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has the largest hospital-based research program in Canada, with major research in cardiology, transplantation, neurosciences, oncology, surgical innovation, infectious diseases, and genomic medicine. University Health Network is a research and teaching hospital affiliated with the University of Toronto.

About International Centre for Genetic Engineering Biotechnology (ICGEB) :-


The ICGEB is an autonomous, intergovernmental organization with its headquarters in Trieste, Italy and two other components in New Delhi, India and Cape Town, South Africa; in addition, ICGEB currently has 57 full Member countries. The ICGEB provides a scientific and educational environment of the highest standard and conducts innovative research in life sciences for the benefit of developing countries. It strengthens the research capability of its members through training and funding programs and advisory services and represents a comprehensive approach to promoting biotechnology internationally.

About Birla Institute of Technology & Science (BITS) :-


The Birla Institute of Technology & Science (BITS), Pilani is an all-India Institute for Higher Education. The research group at BITS has expertise in synthetic chemistry and drug delivery areas with a strong track record of research in medicinal chemistry and drug discovery related areas.

About Lifecare Innovations :-


Lifecare Innovations is an R&D intensive company specializing in controlled release pharmaceuticals employing an array of novel drug delivery technologies. Lifecare Innovations is engaged in the development of number of these controlled release drugs in collaboration with national institutions. These are under various stages of development. Predominant among these are a range of antifungals. In addition, in-house developments for commercialization of technologies have led to the successful launch of several drugs in the market by Lifecare Innovations.

Saturday, December 18, 2010

Aseptic Fill Finish and Lyophilization

Therapure BioPharma is a therapeutic protein-specialized Contract Development and Manufacturing Organization (CDMO) that offers a range of biomanufacturing services including technology transfer & process development, analytical development & testing, scale-up & cGMP manufacturing, aseptic fill/finish, lyophilization and support services.

Therapure is the only Canadian company that offers aseptic fill/finish of glass vials, preformed IV infusion bags and pre-filled syringes at both clinical and commercial scale. Therapure has significant experience, capabilities and capacity for the fill/finish and lyophilization of therapeutic proteins. Within their 130,000 ft2 cGMP facility Therapure has Health Canada- licensed aseptic fill/finish suites for glass vials and validated fill/finish suites for IV infusion bags and pre-filled syringes.

A Mutual Recognition Agreement (MRA) between Health Canada and the EU allows for selected aseptic fill/finished glass vials produced at Therapure to be sold directly into Europe without receiving county pre-inspections. This shortens time to market and allows for lower inventory requirements for Therapure’s European clients.

Therapure offers fill/finish services for their client’s bulk drug substance either produced off-site or as an add-on to Therapure’s own cGMP manufacturing services. Therapure is an ideal partner for biotech companies as they can provide this integrated service from manufacturing to fill/finish to storage and distribution of finished product. Therapure provides lyophilization cycle development and optimization services and in 2010 added commercial lyophilization capacity to its clinical scale lyophilization capabilities allowing production batches in the tens of thousands.

Therapure Biopharma, a proteins development company inspects 100% of the drug product containers prior to final labelling and packaging so as to meet their rigorous quality control standards. Therapure provides warehousing and material handling in their cGMP compliant warehouse for finished goods with next day delivery to clinical and commercial sites throughout North America and Europe.

Therapure’s customer focused flexibility, scientific expertise and scalable capacity allows Therapure to adapt to meet the fill/finish and lyophilization needs of its clients at every stage of the development and commercialization process.

Thursday, December 16, 2010

Biomanufacturing Services Aseptic Fill/Finish and Lyophilization

Significant time and cost have been incurred to produce the bulk drug substance for your program. You are now searching for a partner you can trust to formulate, fill and finish into your desired final product container. Who can you trust with your valuable bulk material? Therapure is your trusted partner for cost-effective clinical and commercial scale fill/finish services.

Aseptic Fill/Finish and Lyophilization Therapure has validated aseptic fill/finish suites for cost effective formulation, filling and finishing of clinical and commercial scale products. Therapure has experience filling and finishing both therapeutic proteins and small molecules into vials, preformed IV bags and prefilled syringes. Therapure also offers integrated lyophilization capabilities at both the clinical and commercial scale.

Our fill/finish suites and support systems were inspected and licensed by Health Canada in 2009. The fill/finish suites are scheduled to undergo multiple FDA pre-approval inspections in 2011.

Aseptic Fill/Finish Services :-
Container Type Validated Equipment Filling Capacity / Hour Container Volumes (mL)
Vial Filling Bosch TL 3,000 X 2 mL vials 2 - 200
Preformed IV Bag Filling Plumat Bag Filler 800 bags 50 – 500
Prefilled Syringe Cozzoli 1,200 x 2mL syringes 0.5-20

Lyophilization Services :-
Scale Chamber Size # Shelves Temp Range Batch to Vial Size Range
Clinical 1.1 m2 (12 ft2) 6 Shelves (114mm) -70 to +650C 4,400 Units x 2mL 2,000 Units x 10mL
Commercial 7.5 m2 (81 ft2) 7 Shelves (100mm) -70 to +800C 32,400 units x 2mL 17,100 units x 5mL 4,000 units x 50mL

Therapure will actively involve you in the implementation of your fill/finish project. Once the product is filled and finished, we perform 100% inspection of the drug product containers prior to labelling, and then finish with packaging and cartoning. We also offer storage and distribution services to your clinical or commercial sites. These services are designed for one goal; to be your one-stop for everything related to aseptic fill/finish & lyophilization.

Thursday, December 9, 2010

Bioanalytical Development And Testing

Therapure operates under the principle, ‘Start with us, stay with us,’ meaning that we provide a range of services to our clients minimizing logistics and creating one point of contact.

 
Supporting every successful drug development program are reliable and robust analytical methods. These methods must be designed to support in-process analysis, bulk release testing, drug product release testing and stability monitoring programs. Who can provide the required support for your method development, qualification and validation needs? Therapure is your trusted partner for developing and validating analytical methods.

Therapure understands the importance of your critical methods and how they support your unique program.

Our facility has 10,600 ft2 of fully equipped analytical development and quality control testing space. Our Bioanalytical Development and quality control teams have extensive experience in the development, qualification, and validation of cGMP compliant analytical methods, including complex biological activity assays. Immediately following project kick-off, our analytical development team begins transferring your established assays or developing products specific assays from scratch. Prior to product manufacturing, the analytical methods are transferred to Therapure’s Quality Control department where they are qualified (for Phase I-II Clinical programs) or validated (for Phase III/Commercial programs) through mutually approved protocols.

Our experience in method development, optimization, qualification and validation includes:-

  • Physiochemical analysis
  • Raw material methods (custom or compendial)
  • Compendial methods (USP, Ph. EU, JP, NF)
Protein concentration (UV-Vis, fluorescence)

  • Spectrophotometry
  • Nephelometry
  • Colorimetric
Gel electrophoresis

  • SDS-PAGE
  • IEF
  • 2-Dimensional
Flow cytometry
ELISA
Cell based bioassays

High performance liquid chromatography

  • Standard (SEC, RP, Ion Exchange)
  • Specialized
Total organic carbon
Gas chromatography (headspace & liquid)

Microbiological testing

  • Microbial identification
  • Endotoxin analysis (gel clot)
  • Particulate matter
  • Sterility
  • Bioburden
Protein characterization

  • Amino acid analysis
  • Peptide mapping and glycoform analysis
  • Extinction coefficient studies
  • Liquid chromatography mass spectroscopy (LC-MS)
Blood/plasma testing

  • Nephelometry
  • HemoX (P50) analysis
  • Co-oximetry
  • Phospholipids

Wednesday, December 8, 2010

Scale Up And cGMP Manufacturing

You have taken your drug candidate as far as you can. It is time to scale up your process from the bench to clinical or commercial size batches. But is your process robust enough? Will it stand up to a 5, 10, 50 or 100 times scale up? Who can you turn to for protein and antibody scale up and cGMP manufacturing experience? Therapure is your trusted partner who can meet your process scale up and cGMP manufacturing needs.


Therapure Biopharma operates a 130,000 ft2 world-class facility with over 28,000 ft2 of cGMP manufacturing space. Operating a range of classified suites from Grade A (Class 100:ISO 5) through Grade C (Class 100,000:ISO 8), Therapure maintains utilities compliant to USP and EP including Water for Injection, Purified Water, Clean Steam and Oil-Free Compressed Air.

During process scale up, Therapure keeps its clients engaged in the project, actively soliciting decisions on raw materials, components, consumables, process specific Standard Operating Procedures (SOPs), Batch Production Records, Analytical Test Methods, Product Specifications and Process Flow Diagrams. We work as an extension of your organization, adding value as your trusted manufacturing partner. When batch manufacturing starts, we encourage clients to be onsite, observing the manufacturing runs with us. Upon completion, we review the run with the client, going through every technical aspect of the batch records in order to fine tune the process for the next run.

Therapure has experience utilizing a variety of different sources of API including :-
  • Whole Blood and Plasma
  • Mammalian Cell Culture
  • Primary Cell Culture
Highlights of our manufacturing capabilities and capacities:-
  • Tissue Processing :-
Dedicated Grade C (Class 100,000:ISO 8) suites through configurable HVAC systems
  1. Upstream :-
  • Mammalian cell culture processes (CHO, HEK-293, Hybridoma, etc.)
  • Microbial processes (through strategic partnerships)
  • Master Cell Bank (MCB) creation
  • Seed train from 5L to 500L Single Use Bioreactors (SUBs)
  • Media preparation up to 6,000L batches
      2.   Midstream :-
  • Harvest by nominal flow filtration, tangential flow filtration or centrifugation
  • Viral inactivation tanks (pH, solvent-detergent, temperature)
  • Nanofiltration
      3.  Downstream :-
  • Dedicated 'non-live' processing area
  • Chromatographic volumetric rates from 10mL/min to 10L/min
  • Ultrafiltration / diafiltration up to 100 m2 of membrane
  • Protein modification (conjugation, refolding, enzymatic conversion, etc.)
  • Buffer preparation up to 6,000L batches
  • Bulk filling

Monday, November 15, 2010

New Venture by Therapure Biopharma for a Human Cause


cell line development and protein production services
Therapure Biopharma is a privately held integrated Contract Development and Manufacturing Organization (CDMO) that was founded in the third quarter of 2008 on the significant experience and manufacturing assets of a successful Canadian biotech company. Since 2008, Therapure has expanded its capabilities and completed a series of facility upgrades that have allowed it to offer an impressive range of integrated biomanufacturing services to its clients.
Therapure provides completely scalable cGMP manufacturing with mg to kg capacity. This allows biotech companies to remain partners with them as their therapeutic protein moves through pre-clinical, clinical and finally to commercial production. Therapure has a track record of working closely with companies of all sizes, from small biotech to large multinationals. Their experience is particularly valuable to biotech companies in solving the technical challenges that they will encounter in the manufacture and fill/finish of complex biologic products. Therapure's integrated services include: technology transfer & process development, analytical development & testing, scale up & cGMP manufacturing, aseptic fill/finish & lyophilization and support services.

Client engagement is important to Therapure to ensure that they are meeting all of their client's CDMO needs. This is accomplished through a collaborative environment that includes joint technical project teams, soliciting input on key processes and finally onsite observation and review of initial production runs.

Throughout 2010 Therapure has signed a series of biomanufacturing and fill/finish contracts and partnerships with international companies helping to build on their positive reputation in the global CDMO industry.

Key accomplishments of 2010 include :-
  • Partnership with Microbix for manufacturing Water For Injection products

  • Fill/Finish contract for pre-filled syringes of Stellar Pharmaceutical’s Neovisc® natural viscosupplement

  • Launch of commercial scale lyophilization services

  • Biomanufacturing agreement with LFB Biomedicaments for two key plasma proteins

  • Fill/Finish contract with Kane Biotech for their proprietary development-stage product

  • Fill/Finish contract with Viron Therapeutics for on-going clinical trials

  • Biomanufacturing contract with ProChon Biotech for their clinical stage therapeutic product

  • Biomanufacturing contract with Diamedica to provide cell line development and protein production services for a diabetes and neurological disorders product

  • Fill/Finish contract with OPK Biotech for the development of an oxygen transport therapeutic product

  • Founding partner of the International Malaria Research Consortium

As a leading Pharmaceutical Contract Manufacturers, Therapure is dedicated to reduce the time, cost, technical and compliance risks of getting their partner's therapeutic protein to market.