Viral Vectors & Plasmid DNA: The Building Blocks of Complex Biologics

November 2019

Till date, more than 20 cell-based therapies have been approved (recent examples include Zynteglo® (2019), Alofisel® (2018), YESCARTA® (2017) and Kymriah® (2017)), while over 500 product candidates are under development. In fact, there are over 1,000 active clinical studies of cell therapies, worldwide. Over the last few years, such therapies have garnered significant attention within the biopharmaceutical industry. Several companies and venture capital funds / investors have already invested a lot of capital towards the development and commercialization of this emerging class of therapeutics. Despite the optimism, the growth in this domain is still hindered by various development and manufacturing related challenges, primarily due to the limited availability of expertise and infrastructure to produce cell-based therapies, such as CAR-T cell therapies. The growing number of product development initiatives in this domain, coupled to the fact that there are multiple marketed products, have led to a substantial rise in the overall cell therapy manufacturing demand. As a result, developers have turned to contract manufacturing organizations (CMOs) to fulfil their cell therapy development and production requirements.  A wide array of industry players, including well-established companies, mid-sized firms and start-ups, as well as academic institutes, are contributing towards fulfilling the aforementioned demand, offering GMP grade manufacturing services for cell therapies. In addition to cell therapy manufacturing companies, there are several other players that claim to have developed novel technology solutions, aimed at improving the existing cell therapy manufacturing process. Many CMOs are also actively expanding their cell therapy manufacturing capacity either through collaborations or acquisitions, in order to offer a wide range of services to their respective clients. As a result of the ongoing efforts aimed at mitigating the existing challenges in this domain, the cell therapy manufacturing market is expected to witness significant growth in mid-long term. Scope of the Report The “Cell Therapy Manufacturing Market (3rd Edition), 2019-2030” features an extensive study of the current market landscape and future opportunities associated with cell therapy manufacturing. It focuses on both contract manufacturers, as well as developers with in-house manufacturing facilities, offering in-depth analyses of the various business entities that are engaged in this domain, across different global regions. Amongst other elements, the report includes: A detailed review of the overall landscape of companies that are engaged in the manufacturing of cell-based therapies, including information on the type of cells manufactured (including immune cells (including T cells, dendritic cells, NK cells), stem cells (including adult stem cells, human embryonic stem cells and induced pluripotent stem cells) and others), source of cells (autologous and allogeneic), scale of manufacturing, type of cell cultures (adherent and suspension), purpose of production (fulfilling in-house requirements and contract services), manufacturing capabilities / services offered (including R&D, cell culture development, quality testing, packaging, labelling, cell banking, cryopreservation, fill / finish services, and regulatory affairs management), location of headquarters and location of their respective manufacturing facilities.  An analysis of the various expansion initiatives undertaken by service providers, in order to augment their respective cell therapy manufacturing capabilities, over the period 2015-2019 (till October), taking into consideration parameters, such as year of expansion, type of cells, scale of operation, purpose of expansion (facility expansion and new facility), location of manufacturing facility, and most active players (in terms of number of expansion initiatives undertaken). An analysis of the recent partnerships focused on the manufacturing of cell-based therapies, which have been established in the period 2014-2019 (till November), based on various relevant parameters, such as the year of agreement, type of partnership, type of cells, and scale of operation (preclinical, clinical and commercial). Informed estimates of the annual commercial and clinical demand for cell therapies (in terms of number of cells produced and area dedicated to manufacturing), which were further analyzed based on type of cells.  An estimate of the overall, installed capacity for manufacturing cell-based therapies based on information reported by industry stakeholders in the public domain, highlighting the distribution of the available capacity on the basis of scale of operation (clinical and commercial), size of the organization (small, mid-sized and large firms) and key geographical regions (North America, EU and Asia Pacific). An in-depth analysis of cell therapy manufacturers using three versatile representations, namely [A] a three dimensional grid analysis, presenting the distribution of companies on the basis of type of cells manufactured, scale of operation and purpose of production, [B] a logo landscape based on the type of cells manufactured, geographical location of manufacturer (North America, Europe and Asia Pacific) and type and size of organization (non-industry players, and small, mid-sized and large companies), and [C] a schematic world map representation, highlighting the geographical locations of cell therapy manufacturing facilities of both industry and non-industry stakeholders. A detailed analysis of the various factors that are likely to influence the pricing of cell-based therapies, featuring different models / approaches that may be adopted by manufacturers while deciding the prices of their proprietary offerings. An elaborate discussion on the role of automation technologies in improving current manufacturing methods, along with a comparative (qualitive) analysis of cost differences between manual and automated processes. A qualitative analysis, highlighting the various factors that need to be taken into consideration by cell therapy developers while deciding whether to manufacture their respective products in-house or engage the services of a CMO. A discussion on cell therapy manufacturing regulations across various geographies, including the North America (focusing on the US), Europe and Asia (focusing on Japan), featuring an analysis of the diverse certifications / accreditations awarded to manufacturing facilities by important regulatory bodies across the globe. Elaborate profiles of key players (industry and non-industry) that offer contract manufacturing services for cell-based therapies; each profile includes an overview of the company / organization, information on its manufacturing facilities, service portfolio details, recent partnerships and an informed future outlook.  A discussion on affiliated trends, key drivers and challenges, which are likely to impact the industry’s evolution, under a comprehensive SWOT framework, which includes a Harvey ball analysis, highlighting the relative effect of each SWOT parameter on the overall market dynamics. Insights generated in a market-wide survey, featuring inputs solicited from experts who are directly and indirectly involved in the development and / or manufacturing of cell-based therapies. One of the key objectives of the report was to understand the primary growth drivers and estimate the future size of the cell therapy manufacturing market. Based on parameters, such as number of ongoing / planned clinical studies, cell therapy manufacturing costs, target patient population, and anticipated adoption of such products, we have provided an informed estimate of the likely evolution of the market in the short to mid-term and mid to long term, for the period 2019-2030. In addition, to account for the uncertainties associated with the manufacturing of cell-based therapies and to add robustness to our model, we have provided three forecast scenarios, portraying the conservative, base and optimistic tracks of the market’s evolution. The opinions and insights presented in the report were also influenced by discussions held with senior stakeholders in the industry. The study includes detailed transcripts of discussions held with the following individuals: Victor Lietao Li (Co-Founder and Chief Executive Officer, Lion TCR)  Tim Oldham (Chief Executive Officer, Cell Therapies) Gerard MJ Bos (Chief Executive Officer, CiMaas) Wei (William) Cao (Chief Executive Officer, Gracell Biotechnologies) Troels Jordansen (Chief Executive Officer, Glycostem Therapeutics)  Arik Hasson (Executive VP Research and Development, Kadimastem) Gilles Devillers (General Manager, Bio Elpida)  Arnaud Deladeriere (Manager, Business Development & Operations-cGMP Manufacturing Unit, C3i Center for Commercialization of Cancer Immunotherapy)  Brian Dattilo (Manager of Business Development, Waisman Biomanufacturing) Fiona Bellot (Business Development Manager, Roslin CT)  Mathilde Girard (Department Leader, Cell Therapy Innovation and Development, Yposkesi) David Mckenna (Professor and American Red Cross Chair in Transfusion Medicine, University of Minnesota) All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

November 2019

According to experts in the healthcare industry, one in three adults are estimated to be suffering from some type of chronic clinical condition, such as multiple sclerosis, diabetes, rheumatoid arthritis and cardiovascular diseases. Chronic clinical conditions are considered to be among the leading causes of death and disability across the world.  Typically, in such cases, individuals are required to medicate on a daily basis. In addition to the cost of medication, such individuals are also burdened with a deteriorating quality of life, and often struggle with medication adherence.  According to the US Centers for Disease Control (CDC), the overall annual expense incurred by those living with chronic diseases is steadily growing and is currently estimated to be more than USD 3 trillion.  The development and commercialization of self-administrable dosage forms of drugs indicated to treat chronic clinical conditions has made a significant positive impact not only on the healthcare expenses borne by patients but also on compliance to prescribed therapeutic regimens. As the number of patients suffering from such disorders increase, the demand for more convenient and patient friendly drug delivery solutions is also on the rise.  Most self-injection devices / systems, such as autoinjectors and pen-injectors,  rely on prefilled syringes, which serve as primary drug containers in the aforementioned products. Moreover, despite having been in the market for more than three decades now, the overall interest in prefilled syringes continues to grow. In fact, the recent increase in use of biologics, which are usually administered via parenteral routes, has had a significant impact on the demand for prefilled syringes.  Over the years, significant improvements have been made to conventional prefilled syringes in order to further expand the scope of their applications. In this context, it is worth mentioning that dual / multi chambered syringes designed for the administration of lyophilized drugs are already available in the market. In such products, the syringe barrel is divided into two chambers, one of which contains the appropriate diluent for the prefilled (lyophilized) drug formulation. Likewise, there are multiple types of specialty syringes, including contrast agent containing syringes and flush syringes. Further, since the introduction and enforcement of the Needlestick Safety and Prevention Act in 2000, several medical device manufactures have developed add-on or integrated safety devices for prefilled syringes. In fact, by 2020, the incorporation of safety features in prefilled syringes is anticipated to be made mandatory across the world.  We are led to believe that the aforementioned developments are likely to fuel innovation and subsequent future growth in this market. Scope of the Report The ‘Prefilled Syringes Market (5th edition), 2019-2030’ report features an extensive study of the current market landscape of prefilled syringes and the likely future opportunities associated with such devices, over the next 10-12 years. It features an in-depth analysis, highlighting the capabilities of various stakeholders engaged in this domain. In addition to other elements, the study includes: An overview of the current market landscape of companies engaged in manufacturing prefilled syringes, providing information on year of establishment, company size, geographical location of the headquarters and manufacturing facilities, type of material used (glass and plastic), number of barrel chambers (single chamber and dual chamber), type of needle system (fixed needle system, luer lock and luer cone) and syringe volume.  An overview of the current market landscape of companies that are developing drugs in combination with prefilled syringes, featuring information on year of establishment, company size, geographical location of the developers, target indication, phases of development, type of drug molecule, route of administration, approval year (for marketed products), dosage details (for marketed products) and other approved dosage forms (for marketed products).  A detailed competitiveness analysis of the various prefilled syringes that we came across, taking into consideration the supplier power (based on the employee size of developer / manufacturer and their respective annual revenues) and key product specifications, such as number of chambers in the barrel, number of needle systems, volume of the barrel, technological advancement / user-friendliness and other distinguishing features. A list of marketed drugs / therapies and pipeline candidates that are likely to be developed in combination with prefilled syringes in the near future, shortlisted based on an in-depth analysis that takes into consideration various relevant parameters, such as route of administration, type of drug molecule, target indications, other available dosage forms (for approved drugs) and historical annual sales information (for approved drugs). An analysis presenting potential strategic partners (primarily drug developers) for prefilled syringe manufacturers (with regard to likely collaboration opportunities for combination product development) based on different parameters, such as pipeline strength, target therapeutic indication(s) and developer strength. An analysis of the various prefilled syringe combination product-related initiatives of big pharma players, based on parameters, such as current adoption (based on number of approved and under development prefilled syringe combination products) and likely future adoption (based on potential injectable product candidates in the pipeline that are likely to be delivered via prefilled syringes), target therapeutic area(s) and type of drug molecule. A review of the landscape of contract fill / finish services providers that offer services for prefilled syringes, featuring a list of active (large-sized) service providers and analysis based on a number of relevant parameters, such as year of establishment, company size, scale of operation (preclinical, clinical and commercial), type of drug molecule (biologics and small molecules), and geographical location of the service provider.  A detailed discussion on various safety features (add-on and integrated devices) installed in recent versions of prefilled syringes and the companies involved in developing and manufacturing such solutions. An informative summary of various guidelines established and issued by major regulatory bodies for the approval of prefilled syringes, across different countries / geographical regions.   Brief discussions of currently available specialty syringes, which include prefilled flush syringes, prefilled diluent syringe systems and prefilled contrast agent delivery systems.  A case study on companies that are engaged in the manufacturing of autoinjectors, featuring brief profiles of key players in this domain; each profile includes an overview of the firm, and information on its respective product portfolio. Elaborate profiles of prominent prefilled syringe manufacturers engaged in this domain, featuring a brief overview of the company, its financial information (if available), information on product portfolio, recent developments and an informed future outlook. Elaborate profiles of prominent prefilled syringe component manufacturers, featuring a brief overview of the company, its financial information (if available), information on product portfolio, recent developments and an informed future outlook. One of the key objectives of the report was to evaluate the current market size and the future opportunity within the prefilled syringes market. Based on various relevant parameters, such as the number of commercialized combination products, annual adoption rate, and expected pricing, we have provided an informed estimate of the likely evolution of the market over the period 2019-2030. In order to provide a detailed future outlook, our projections have been segmented on the basis of [A] therapeutic area (blood disorders, infectious diseases, autoimmune disorders, oncology disorders, neurological disorders, ophthalmic diseases and others), [B] type of syringe, [C] type of material (glass and plastic), [D] number of chambers (single chamber and dual chamber),  [E] type of drug molecule (antibodies, proteins, vaccines, small molecules, peptides, and others), and [F] key geographies (North America, Europe (the UK, France, Italy, Spain, Germany and the rest of Europe), Latin America (Brazil, Mexico, Argentina and the rest of Latin America), Asia Pacific (Japan, China, India, South Korea and the rest of Asia Pacific), and the Middle East and Africa (Saudi Arabia, UAE, Africa and the rest of the Middle East)).  The research, analysis and insights presented in this report are backed by a deep understanding of key insights gathered from both secondary and primary research. The opinions and insights presented in the report were influenced by discussions held with several players in this industry. The study includes detailed transcripts of discussions held with the following individuals: Matthew Young (Founder and Chief Technology Officer, Oval Medical Technologies) Kirti Maheshwari (Chief Technical Officer, Intas Pharmaceuticals) Gregor Kawaletz (Chief Commercial Officer, IDT Biologika) Kevin Cancelliere and Tibor Hlobik (Marketing Directors, West Pharmaceutical Services) Marco Pederiva (Marketing & Sales Director, Lonstroff) Anonymous (Chief Executive Officer, Small-sized Medical Device Company) All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

November 2019

According to the World Bank, more than 50,000 different types of medical devices are currently being used on a daily basis in healthcare facilities across the globe. In 2018, the global medical devices market was estimated to have reached a net worth of approximately USD 450 billion. It is also worth noting that, since January 2018, the USFDA approved over 130 medical devices. However, a relatively large proportion of developers lack the resources and technical expertise required to handle regulatory filings and effectively manage the processes associated with procuring marketing authorizations from regional regulators. Moreover, keeping up with evolving regulatory guidelines, rising costs of legal advice and increasing effort required for preparing of technical documentation, is difficult for companies with limited finances. In addition, establishing reimbursement strategies for medium to high-risk devices is also a complicated process and innovator companies usually do not have the expertise to deal with payers and insurance providers. According to a recent report, 68% of medical device companies reports prepared and submitted by in-house players are either rejected or were reported to have multiple major gaps in their clinical evaluation report (CER) and supporting evidences by the notified bodies. In fact. in a survey published in the 2016 edition of Global Medical Device Supply Chain, regulatory requirements were highlighted among the primary areas of concern within the medical device value chain. Furthermore, the implementation of highly stringent regulatory guidelines, specifically for devices posing medium to high risk to consumers, render them subject to rigorous quality assessments.  The aforementioned challenges have led many medical device developers, especially the smaller players and certain established companies as well, to outsource parts of their regulatory operations to capable contract research organizations (CROs). Generally, CROs are known to offer a number of benefits, which include cost benefits, reductions in time-to-market and, in this specific case, an in-depth and up-to date regulatory support. Given that the global demand for medical devices is increasing at a substantial pace, the opportunity for CROs with expertise in regulatory affairs management is also on the rise. In the foreseen future, the growing complexity of regulatory processes across various developing and developed geographies is likely to prompt more developers to outsource various aspects of their dealings with regulatory authorities. Moreover, in order to cope up with latest changes in medical device-related regulations, several legacy CROs are re-evaluating their operational models and business strategies. Owing to the anticipated rise in demand for such services, the contract regulatory services domain is likely to witness the entry of a number of new players in the foreseen future. Scope of the Report The ‘Contract Regulatory Affairs Management Market for Medical Devices, 2019-2030’ report features a detailed study on the current landscape of contract service providers focused on regulatory affairs management for medical devices. The study features an in-depth analysis, highlighting the capabilities of the various CROs engaged in this domain, across different regions of the globe. Amongst other elements, the report includes: A detailed review of the current market landscape of the medical devices regulatory affairs outsourcing market, featuring a list of over 400 CROs engaged in this domain, and detailed analysis based on a number of relevant parameters, such as year of establishment, size of employee base, geographical location, device class (class I, class II, and class III), type and size of clientele (medical device developers, medical device manufacturers, medical device research organizations, and others), types of services offered, ([A] regulatory management services (such as legal representation, notified body selection, project registration and clinical trial application, regulatory writing and publishing, regulatory document submission, product labelling related service, gap analysis, technical dossier set-up, vigilance & medical device report, risk management-related services), [B] additional services (such as biostatistics, consulting, clinical operations, post-marketing activities, quality assurance, reimbursement, training)), region(s) of operation wherein the company is offering regulatory management services, and popular therapeutic area(s).  A detailed discussion on the need for regulatory review / oversight across different stages of the medical devices supply chain, with emphasis on the optimization of the supply chain using upcoming tools / technologies (such as artificial intelligence, big data analytical, blockchain, internet of things and others). An elaborate discussion on the various guidelines established by major regulatory bodies for medical device approval across North America (the US, Canada and Mexico), Europe (France, Germany, Italy, Spain, the UK and rest of Europe), Asia-Pacific and rest of the world (Australia, Brazil, China, India, Israel, Japan, New Zealand, Singapore, South Africa, South Korea, Taiwan, and Thailand). The report also features an insightful multi-dimensional, heat map analysis, featuring a comparison of the contemporary regulatory and reimbursement scenarios in key geographies across the globe. Elaborate profiles of popular players that specialize in offering end-to-end regulatory services for medical devices across key geographies (North America, Europe and Asia-Pacific). Each profile features a brief overview of the company, including information on company headquarters, year of establishment, number of employees, and therapeutic area expertise, financial information (if available), detailed description of service portfolio, and an informed future outlook. A benchmark analysis, highlighting the key focus areas of small-sized, mid-sized and large companies, comparing their existing capabilities within and beyond their respective peer groups, providing a means for stakeholders to identify ways to gain a competitive edge in the industry. An elaborate discussion on the various outsourcing business models adopted for regulatory affairs management, along with an insightful Harvey ball analysis of key considerations that need to be assessed by industry stakeholders while selecting a CRO partner. An analysis highlighting the key performance indicators used by sponsor companies to evaluate service providers that are active in the domain, based on information gathered via secondary research (for top-ten medical device players) and primary research. A survey analysis featuring inputs solicited from various experts who are directly / indirectly involved in providing regulatory affairs management services to medical device developers.  One of the key objectives of this report was to evaluate the current opportunity and the future potential of the medical device regulatory affairs outsourcing market over the coming decade. We have provided an informed estimate of the likely evolution of the market in the short to mid-term and long term, for the period 2019-2030. In addition, we have provided the likely distribution of the opportunity across different [A] types of regulatory affair management service offered (legal representation, project registration and clinical trial application, regulatory writing and publishing  and 6+ categories) [B] device class (class I, class II and class III), [C] therapeutic areas (cardiovascular disorders, central nervous system (CNS) disorders, metabolic disorders, oncological disorders, orthopedic disorders, ophthalmic disorders, pain disorders, respiratory disorders, and others), and [D] geographical regions (North America, Europe, Asia-Pacific and rest of the world). To account for the uncertainties associated with the growth of the medical device regulatory affairs outsourcing CRO market and to add robustness to our model, we have provided three forecast scenarios, portraying the conservative, base and optimistic tracks of the market’s evolution. The opinions and insights presented in the report were also influenced by discussions held with senior stakeholders in the industry. The report features detailed transcripts of interviews held with the following industry stakeholders (in alphabetical order of company name):  Tania Persson, Business Development Manager, A+ Science Alexa Foltin-Mertgen, Business Development Manager, AtoZ-CRO Troy Mccall, Chief Operating Officer, CROMSOURCE Christian Wolflehner, Managing Director, Clinical Trial Specialist, CW Research & Management Antal Solyom, Director, Medical Device Unit, HungaroTrial Nazish Urooj, Senior manager, Medical & Clinical Operations, Metrics Research C Omprakash, Technical Director and Partner, Vyomus Consulting  All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.