Kristin Brooks, Managing Editor05.07.18
Early drug development is growing more imperative as drug developers want to pursue only those candidates that will lead to greater safety and efficacy profiles down the road. Also, with the therapeutic research areas of oncology and immunology growing rapidly and discovery research in these areas becoming increasingly complex, specialized capabilities are needed to develop today’s next-gen therapeutics.
Pharma and biopharma companies traditionally keep discovery work in-house, but as preclinical CROs offer experience and highly specialized capabilities, they’re increasingly outsourcing this sensitive research work. This growth in outsourcing early development provides an opportunity for contract research organizations to develop portfolios of early discovery services that accommodate sponsor needs.
Charles River Laboratories recently acquired MPI Research for approximately $800 million, expanding its client base, providing access to growing end markets, building scale, and expanding its service portfolio. Also, earlier this year Charles River acquired KWS BioTest, a contract research organization specializing in in vitro and in vivo discovery testing services for immuno-oncology, inflammatory and infectious diseases, for roughly $20 million, enhancing its discovery services in the burgeoning therapeutic research areas of oncology and immunology.
In addition to these recent acquisitions, Charles River recently announced several key expansions to its global biologics testing solutions infrastructure to support the characterization, development, and release of biologics and biosimilars. Growth in this industry has led to increased demand for outsourced services and Charles River is taking this opportunity to enhance capacity and capabilities.
The company added a new, 73,000 sq.-ft. facility in Wayne, PA, more than doubling lab space at the company’s existing facilities in Malvern and King of Prussia, PA. In Malvern, 2,800 sq.-ft. of new clean rooms will be dedicated to GMP microbial and mammalian cell banking, increasing cell banking capacity by 40 percent.
Additionally, in Shrewsbury, MA, Charles River is combining and expanding the services offered in Malvern and Woburn, MA under one roof in an effort to speed up method development and increase offerings for analytical and protein characterization services.
Meanwhile, in Erkrath, Germany, 4,500 sq.-ft. of new lab space will be designed to meet the special requirements of bioactivity testing, expanding offerings for the development, transfer, and optimization of bioassay methods, including support for lot release, stability testing, and the comparability testing of biosimilar products.
Finally, in Ballina, Ireland, additional assays have been introduced, including in vitro adventitious agent and mycoplasma testing, along with the full suite of in vivo biosafety testing methods.
Contract Pharma spoke with Greg Beattie, corporate vice president, Global Biologics Testing Solutions at Charles River, about the preclinical market and outsourcing, demand for early research services and the capabilities needed. Contract Pharma also spoke with Andy Vick, site director, Mattawan and corporate vice president, Safety Assessment at Charles River, regarding the company’s recent acquisition of MPI Research.
Contract Pharma: How has the preclinical market evolved over the last few years?
Greg Beattie: Transparency Market Research states that the global biologics market will expand at a healthy 10.9% CAGR from 2016 to 2024. The growth in demand for preclinical services has been the result of a combination of more drugs in development pipelines, a greater emphasis on early-stage development, and an influx of both biosimilar products and more complex drugs such as antibody-drug conjugates (ADCs) and gene therapies.
Concurrent with this growth, there has been some consolidation among providers of preclinical services, resulting in less fragmentation within the sector and the rise of some major providers that are better prepared to satisfy the market’s outsourcing needs.
CP: What are some of the factors driving demand for early research services?
GB: In biologics, the need to quickly screen promising therapeutics candidates and weed out those that demonstrate poor safety profiles is significantly driving the outsourcing of early research. This approach results in significant savings for developers, ensuring that efforts and resources are being focused on the drug candidates that are more likely to succeed.
Another factor is the development of more complex drugs, such as ADCs, that have the potential to be very toxic and thus require more extensive preclinical scrutiny before moving onto clinical trials.
The rise of outsourced research and development (R&D), along with the recognized competency of contract research organizations (CROs) in delivering on-time, quality services, are also propelling higher demand for early research services.
CP: What are the latest biopharma trends and what opportunities do they present for preclinical outsourcing?
GB: While monoclonal antibodies and recombinant proteins will continue to dominate the biopharmaceutical market, new therapeutic modalities are gaining significant traction. These include gene and cell therapies, tissue replacement and regeneration and microbiome modulation.
These new categories of products not only require significant preclinical analysis to ensure patient safety but will likely require novel preclinical approaches to properly address toxicity, biological activity, dosing regimen and public health risks.
CP: What new capabilities are required for today’s biologics and biosimilars development?
GB: There are two immediate needs: the first is highly sensitive assays to monitor and detect drug immunogenicity, and the second is potency-based “biosimilarity” assays that can capture the value-proposition of a biosimilar or bio-better molecule.
Additionally, as more “personalized” manufacturing methods mature we will need more highly sensitive analytical methods. These range from chromatography to mass spectrometry and biophysical techniques, and ultimately permit measurements of minor impurities and subtle changes in physical, chemical and biological properties within an active substance, and are ultimately predictive of potential safety issues. Better data-driven assessment will be key to this.
Another critical manufacturing safety area is advanced “biosafety” testing—especially for possible viral, bacterial and other microbial contaminants for both monoclonals, as well as cell- and gene-therapy products. Finally, a better integration of the “supply-chain” for newer biologics is needed, including cell and gene therapy, from sample collection in patients through cellular and genetic engineering, all the way to therapeutic application back in patients.
CP: What specific services are increasingly being outsourced?
GB: Toxicology has been by far the preclinical service in most demand for biologics. Other services in high demand include bioanalysis and DMPK studies. On the early discovery side of the biologics industry, there is significant demand for cell line development and cell banking, early-formulation and process optimization, active substance characterization, development of analytical methods for product release and stability assessment and qualification and validation of related analytical methods.
CP: What are some of the latest motivators for sponsors with respect to outsourcing?
GB: A major motivator to outsource is the desire to accelerate development and manage risks better. CROs are often more efficient, having developed ways to reduce timelines that result in the Sponsor getting their drug to market faster. With increased efficiency and shortened timelines, there is a significant decrease in development expenditures. Another motivator is “early screening” through preclinical CROs, to screen drug candidates in depth and more efficiently to provide strategic go/no-go decisions for those candidates with poor pharmacology and toxicology profiles.
The recent consolidation in the preclinical CRO industry has resulted in an increase in competency among the remaining CROs; this increase in competency has, in-turn, been fueling additional outsourcing. In addition, the increasing outsourcing practices over the last few years by some of the large pharma companies have forced others in the industry to participate in this outsourcing environment to maintain competitiveness.
CP: What is your perspective on where R&D is going and where do you think some of the biggest opportunities lie?
GB: R&D is shifting to more complex drugs such as bispecific antibodies, ADCs, gene and cell therapies and tissue replacement or regeneration. Opportunities lie in developing the appropriate lines of nonclinical, preclinical and clinical services to address the needs of these new types of therapy.
For the early development and preclinical services, there will be great opportunity in developing in-vitro and in-silico technologies that will be predictive of drug safety and biological activity or, even better, clinical efficacy.
Additionally, for cell and gene therapies, R&D will be increasingly tied into manufacturing quality and final product safety through process engineering and end-to-end process efficiencies.
CP: What were the main drivers behind the MPI acquisition?
Andy Vick: The acquisition of MPI aligns with our strategy to expand our biotechnology client base, which MPI has specialized in. They are recognized for their scientific expertise, flexible and responsive project management, and client service. Additionally, MPI will add ototoxicity and abuse liability capabilities, and expand our existing capabilities in general toxicology and specialty toxicology, including ophthalmology, juvenile toxicity, molecular biology, and surgery, as well as medical device testing. MPI will also provide safety assessment infrastructure to support current demand and future growth needs.
CP: In what areas do you expect to gain scope/scale as a result of the acquisition?
AV: MPI offers diverse service lines that compliment the capabilities we currently offer and add to our existing expertise. These services include: ADME, analytical chemistry, regulated and discovery bioanalytical (both large and small molecule), DART, experimental therapeutics, general toxicology, imaging, infusion toxicology, PK/TK data analysis, neurobehavioral sciences, discovery DMPK, safety pharmacology, surgery, ototoxicology, ophthalmology, abuse liability, juvenile toxicology, molecular biology, and SEND.
Pharma and biopharma companies traditionally keep discovery work in-house, but as preclinical CROs offer experience and highly specialized capabilities, they’re increasingly outsourcing this sensitive research work. This growth in outsourcing early development provides an opportunity for contract research organizations to develop portfolios of early discovery services that accommodate sponsor needs.
Charles River Laboratories recently acquired MPI Research for approximately $800 million, expanding its client base, providing access to growing end markets, building scale, and expanding its service portfolio. Also, earlier this year Charles River acquired KWS BioTest, a contract research organization specializing in in vitro and in vivo discovery testing services for immuno-oncology, inflammatory and infectious diseases, for roughly $20 million, enhancing its discovery services in the burgeoning therapeutic research areas of oncology and immunology.
In addition to these recent acquisitions, Charles River recently announced several key expansions to its global biologics testing solutions infrastructure to support the characterization, development, and release of biologics and biosimilars. Growth in this industry has led to increased demand for outsourced services and Charles River is taking this opportunity to enhance capacity and capabilities.
The company added a new, 73,000 sq.-ft. facility in Wayne, PA, more than doubling lab space at the company’s existing facilities in Malvern and King of Prussia, PA. In Malvern, 2,800 sq.-ft. of new clean rooms will be dedicated to GMP microbial and mammalian cell banking, increasing cell banking capacity by 40 percent.
Additionally, in Shrewsbury, MA, Charles River is combining and expanding the services offered in Malvern and Woburn, MA under one roof in an effort to speed up method development and increase offerings for analytical and protein characterization services.
Meanwhile, in Erkrath, Germany, 4,500 sq.-ft. of new lab space will be designed to meet the special requirements of bioactivity testing, expanding offerings for the development, transfer, and optimization of bioassay methods, including support for lot release, stability testing, and the comparability testing of biosimilar products.
Finally, in Ballina, Ireland, additional assays have been introduced, including in vitro adventitious agent and mycoplasma testing, along with the full suite of in vivo biosafety testing methods.
Contract Pharma spoke with Greg Beattie, corporate vice president, Global Biologics Testing Solutions at Charles River, about the preclinical market and outsourcing, demand for early research services and the capabilities needed. Contract Pharma also spoke with Andy Vick, site director, Mattawan and corporate vice president, Safety Assessment at Charles River, regarding the company’s recent acquisition of MPI Research.
Contract Pharma: How has the preclinical market evolved over the last few years?
Greg Beattie: Transparency Market Research states that the global biologics market will expand at a healthy 10.9% CAGR from 2016 to 2024. The growth in demand for preclinical services has been the result of a combination of more drugs in development pipelines, a greater emphasis on early-stage development, and an influx of both biosimilar products and more complex drugs such as antibody-drug conjugates (ADCs) and gene therapies.
Concurrent with this growth, there has been some consolidation among providers of preclinical services, resulting in less fragmentation within the sector and the rise of some major providers that are better prepared to satisfy the market’s outsourcing needs.
CP: What are some of the factors driving demand for early research services?
GB: In biologics, the need to quickly screen promising therapeutics candidates and weed out those that demonstrate poor safety profiles is significantly driving the outsourcing of early research. This approach results in significant savings for developers, ensuring that efforts and resources are being focused on the drug candidates that are more likely to succeed.
Another factor is the development of more complex drugs, such as ADCs, that have the potential to be very toxic and thus require more extensive preclinical scrutiny before moving onto clinical trials.
The rise of outsourced research and development (R&D), along with the recognized competency of contract research organizations (CROs) in delivering on-time, quality services, are also propelling higher demand for early research services.
CP: What are the latest biopharma trends and what opportunities do they present for preclinical outsourcing?
GB: While monoclonal antibodies and recombinant proteins will continue to dominate the biopharmaceutical market, new therapeutic modalities are gaining significant traction. These include gene and cell therapies, tissue replacement and regeneration and microbiome modulation.
These new categories of products not only require significant preclinical analysis to ensure patient safety but will likely require novel preclinical approaches to properly address toxicity, biological activity, dosing regimen and public health risks.
CP: What new capabilities are required for today’s biologics and biosimilars development?
GB: There are two immediate needs: the first is highly sensitive assays to monitor and detect drug immunogenicity, and the second is potency-based “biosimilarity” assays that can capture the value-proposition of a biosimilar or bio-better molecule.
Additionally, as more “personalized” manufacturing methods mature we will need more highly sensitive analytical methods. These range from chromatography to mass spectrometry and biophysical techniques, and ultimately permit measurements of minor impurities and subtle changes in physical, chemical and biological properties within an active substance, and are ultimately predictive of potential safety issues. Better data-driven assessment will be key to this.
Another critical manufacturing safety area is advanced “biosafety” testing—especially for possible viral, bacterial and other microbial contaminants for both monoclonals, as well as cell- and gene-therapy products. Finally, a better integration of the “supply-chain” for newer biologics is needed, including cell and gene therapy, from sample collection in patients through cellular and genetic engineering, all the way to therapeutic application back in patients.
CP: What specific services are increasingly being outsourced?
GB: Toxicology has been by far the preclinical service in most demand for biologics. Other services in high demand include bioanalysis and DMPK studies. On the early discovery side of the biologics industry, there is significant demand for cell line development and cell banking, early-formulation and process optimization, active substance characterization, development of analytical methods for product release and stability assessment and qualification and validation of related analytical methods.
CP: What are some of the latest motivators for sponsors with respect to outsourcing?
GB: A major motivator to outsource is the desire to accelerate development and manage risks better. CROs are often more efficient, having developed ways to reduce timelines that result in the Sponsor getting their drug to market faster. With increased efficiency and shortened timelines, there is a significant decrease in development expenditures. Another motivator is “early screening” through preclinical CROs, to screen drug candidates in depth and more efficiently to provide strategic go/no-go decisions for those candidates with poor pharmacology and toxicology profiles.
The recent consolidation in the preclinical CRO industry has resulted in an increase in competency among the remaining CROs; this increase in competency has, in-turn, been fueling additional outsourcing. In addition, the increasing outsourcing practices over the last few years by some of the large pharma companies have forced others in the industry to participate in this outsourcing environment to maintain competitiveness.
CP: What is your perspective on where R&D is going and where do you think some of the biggest opportunities lie?
GB: R&D is shifting to more complex drugs such as bispecific antibodies, ADCs, gene and cell therapies and tissue replacement or regeneration. Opportunities lie in developing the appropriate lines of nonclinical, preclinical and clinical services to address the needs of these new types of therapy.
For the early development and preclinical services, there will be great opportunity in developing in-vitro and in-silico technologies that will be predictive of drug safety and biological activity or, even better, clinical efficacy.
Additionally, for cell and gene therapies, R&D will be increasingly tied into manufacturing quality and final product safety through process engineering and end-to-end process efficiencies.
CP: What were the main drivers behind the MPI acquisition?
Andy Vick: The acquisition of MPI aligns with our strategy to expand our biotechnology client base, which MPI has specialized in. They are recognized for their scientific expertise, flexible and responsive project management, and client service. Additionally, MPI will add ototoxicity and abuse liability capabilities, and expand our existing capabilities in general toxicology and specialty toxicology, including ophthalmology, juvenile toxicity, molecular biology, and surgery, as well as medical device testing. MPI will also provide safety assessment infrastructure to support current demand and future growth needs.
CP: In what areas do you expect to gain scope/scale as a result of the acquisition?
AV: MPI offers diverse service lines that compliment the capabilities we currently offer and add to our existing expertise. These services include: ADME, analytical chemistry, regulated and discovery bioanalytical (both large and small molecule), DART, experimental therapeutics, general toxicology, imaging, infusion toxicology, PK/TK data analysis, neurobehavioral sciences, discovery DMPK, safety pharmacology, surgery, ototoxicology, ophthalmology, abuse liability, juvenile toxicology, molecular biology, and SEND.
