Therapure's Biotech Manufacturing targets Clients' Scale Up & cGMP Manufacturing needs

Therapure Biopharma is a Contract Development and Manufacturing Organization (CDMO) that specializes in the development, scale up and manufacture of protein therapeutics and protein purification. Therapure operates a modern 130,000 ft2 cGMP facility that is equipped with Class A to C clean rooms, QC and analytical labs, clinical and commercial scale manufacturing suites, mammalian cell culture production capability with upstream and downstream processing and aseptic fill/finish capacity. This facility coupled with the skilled staff provides clients with a complete range of integrated biomanufacturing services.

Technology Transfer & Process Development :-

The technology transfer program combines Therapure's significant experience developing protein-based products with clients’ product specific knowledge to create a cost-effective and efficient development program. Therapure’s process development services include: vector design and construction, host cell line optimization, cell banking, upstream & downstream processing and buffer formulation development.

Analytical Development & Testing :-

Therapure can support client needs with robust and reliable analytical methods that are used to support in-process analysis, bulk and drug product release testing and stability monitoring programs. Therapure has expertise in developing product specific assays and in the development, qualification and validation of cGMP compliant analytical methods including complex biological activity assays.

Scale Up & cGMP Manufacturing :-

With 28,000 ft2 of cGMP manufacturing space including pilot, clinical and commercial scale production capacity Therapure is able to meet their client’s scale up needs. Therapure has >20 years of experience manufacturing a variety of sources of API covering mammalian cell culture, whole blood and plasma and primary cell culture. Upstream capabilities include: CHO, HEK-293, hybridoma and stem cell culture, master cell bank creation and media preparation. Downstream expertise includes, protein purification, protein modification and large scale buffer preparation. Therapure is a recognized global leader in their expertise in the production and purification of whole blood and plasma products.

Aseptic Fill/Finish & Lyophilization :-

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 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 Canada and the EU allows for selected aseptic fill/finished glass vials produced at Therapure to be sold directly into Europe without receiving country pre-inspections. Lyophilization development and optimization services are available along with clinical and commercial scale lyophilization capacity.

Support Services :-

Therapure’s support services were designed to provide a complete biomanufacturing service offering, thereby minimizing logistics and providing one point of contact. Warehousing and material handling are provided with 24/7 access control and monitoring in a range of environments including freezers, walk-in cold rooms, incubators and explosion rated rooms. Therapure's validated shipping protocols allow them to provide next day delivery in North America and Europe. Therapure also offers validation support and stability testing compliant with ICH guidelines.

Therapure's diverse group of clients continues to value the quality systems and broad range of biomanufacturing services that Therapure provides. The integrated service offering allows clients to remain with Therapure throughout the development and commercialization stages of production.

Developing Biopharmaceuticals

Located in Mississauga, Ontario, Therapure Biopharma is an integrated biopharmaceutical company that develops, manufactures, purifies, and packages therapeutic proteins.

It’s not as complicated as it sounds. If you ask Thomas Wellner, President and CEO of Therapure, he explains what his company does in easier terms. In his words, “Therapure’s primary business focus is to perform contract development and manufacturing services (CDMO) for biotech and pharmaceutical companies. The company specialises in biologics, which are different than pills or small molecules. Biologics are gleaned from a living source; for example, a cell, bacteria or an animal.” Consistency of manufacturing is critical for biologics since the process starts with a living source.

Therapure attracts large, multinational pharmaceutical and biotech customers, as well as small, start-up biotech companies. Providing development and biomanufacturing services allows Therapure to stay at the forefront of biomanufacturing techniques, ensuring clients benefit from both depth in the scale up of a manufacturing process, as well as the breadth of potential sources to manufacture biologics. The second aspect to the business is pursuing their own discovery research—also focused on biologics.

“We are developing a set of products that is focused around using haemoglobin—the body’s most abundant protein—as a drug carrier,” explains Wellner. “We attach drugs to haemoglobin and it naturally transports the drugs to organs like the liver, spleen and bone marrow. It’s an efficient use of a natural process to get a drug to the body. Therapure is also doing development work for rare blood disorders, bone growth and bone regeneration.”

The product side is still in its early stages of development. Some of their products won’t go into the clinic for testing for another year or two. Even after that, they won’t be approved for a while. “The drug approval process is at least five years,” Wellner says. “You have to do clinical work just for proof of concept and then you need to perform pharmacokinetic toxicological studies that are required by the health regulators to allow you to go into Phase One clinical studies in healthy volunteers.”

Phase One involves trying the product on a healthy person. Phase Two looks at a few people with a particular disorder, and in Phase Three, you do tests on a broader population to make sure it’s safe and efficacious. “After all that, you provide the data that’s been analysed to gain marketing approval. And that process can take six to eight years and many millions of dollars,” says Wellner.

Industry Trends :-

As research, technology and knowledge advance, the medical industry experiences constant change. One of the major trends that has been significant for Therapure Biopharma is the growth in demand for biologics. “The growth has been tremendous in vaccines and monoclonal antibodies,” says Wellner. “The biologics industry is growing at three times the rate of general growth in medicine. Biologics are being used to target diseases and areas of the body that previously couldn’t be treated.”

Another positive change affecting the company is the desire to outsource. Ten years ago, pharmaceutical companies did everything inside their own walls, reluctant to use service providers. Due to the economic climate, there has been a shift in the way pharmaceutical companies are spending. “They are trying to use capital in the areas they’re good at and outsource for non-core areas,” Wellner explains. “The trend to partner with biomanufacturing and drug development services has been great for us. That’s why we’re in the services business, because the trend has been so strong.”

Will the trend reverse when the economy turns around? Maybe not. Wellner believes it’s sustainable. It might be the industry is realizing that this is an efficient way to focus their capital on high-value areas, while allowing competent service providers to provide support.

No matter what industry, money is always a concern. Who pays for particular products in the system is something that is certainly becoming more prevalent, as is building a case for financial support. Twenty years ago, there was a lot more freedom around what a system would provide and pay for. In his last 10 years, Wellner has seen a real tightening on which products gain support and approval for funding from centrally funded Government systems.

“Now, you have to spend a lot more time providing health-economic information and arguments that are non-scientific in nature,” says Wellner, “You have to include a cost-benefit analysis. For us, it’s difficult yet important because the types of products that we’re involved in are usually unique, expensive and specific to rare disorders. The use of these products is being controlled and it is more challenging to get them paid for.”

Ramping up :-

As Canada invests more in developing its healthcare and medical industries, Therapure Biopharma, a Biotech Manufacturing organization is one of those companies that is sure to succeed since the company provides high-value services which are not widely available from one service provider. Positioning itself for that success, Therapure is aggressively ramping up their client base to build revenue.

“We have invested a lot of time, capital and effort into getting our facility up to full capacity so we want to make sure our cash in is equal to or exceeding our cash out,” reasons Wellner. “We booked positive revenues last year and we have an aggressive revenue growth plan for 2009 and beyond.”

“The long-term goal is to continue to see that services revenue grow and to have some of the early investments start to bear fruit,” Wellner concludes. “Some of the internal developments and joint-development products will start to create some additional uplift for our business that will allow us to continue to grow nicely. Eventually, Therapure wants to be a fully integrated biopharmaceutical company that provides both services to others and also has our own innovative products to sustain long term growth.”

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.

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

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

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.

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.

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.

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.