Transforming quality management is the underlying goal of Quality 4.0 (1), a global, cross-industry initiative that pursues quality excellence through digital transformation. Disruptive technologies that connect systems, processes, and people provide the foundation for quality transformation by enabling pharmaceutical companies to become more proactive in addressing quality issues throughout the product lifecycle.

	Quality 4.0 offers significant potential for life-sciences companies, though many are still uncovering new ways to leverage the initiative across their organizations. Early requirements for electronic records and signatures set by FDA prompted a movement to digital technology in the early 1990s, but efforts to go digital in quality were limited to specific process areas. At the time, quality was not viewed as a strategic area in life sciences, so less emphasis was placed on making holistic, sweeping changes. Instead, companies implemented digital technology in piecemeal, plant by plant, or reactively, as a way to address specific issues. The result was system fragmentation.

	Companies today use one or more discrete quality management systems (QMS) for change control, complaints management, audits, and other applications. These disparate systems cannot seamlessly support end-to-end processes and create inefficiency. Additionally, management cannot easily see how this patchwork of systems impacts the company’s overall business, making it difficult to build a convincing case for transformative change. 

	The Quality 4.0 movement coupled with globalization, compliance changes, and pressures to operate more efficiently, are driving transformation, however. Already, 18 of the world’s top 20 pharmaceutical companies are either transforming or planning to transform at least one area of quality management with modern cloud technology. A cloud-based quality management platform that connects all quality systems enables organizations to bring products to market faster while ensuring quality and compliance. 

	Quality 4.0 is now within reach, and the results will be transformative. However, quality managers must first build the right business case to ensure that the entire organization is in sync. The key is to first map all of the benefits with the business goals, and measuring each quality outcome against business values.

	Adopting new transformative technology is not easy, because it requires more than changing technologies. It requires changing minds. This effort is usually driven by a visionary leader or forced by management after a major regulatory action, such as a warning letter. Further, most quality teams have only implemented projects incrementally over the past 25 years, so a single transformation project designed to overhaul everything is going to require careful planning and a strategic case that aligns benefits with business goals. To succeed, the strategy must shift from focusing predominantly on cost to added value. From a system perspective, four key areas are enabling change, driving transformation and value generation:

-A cloud platform provides a modern, consumer-inspired user experience that is always current with regular system updates. It becomes an appreciating asset over time because it works better with more use.

-Process standards that align with best practices eliminate the need to go through massive requirement definitions and configuration exercises. As a result, they enable the standardization of metrics for better reporting, smoother new-hire transitions within the organization, and shorter overall development cycles.

-With a unified systems model, companies bring together multiple, disparate applications onto a single global platform for greater visibility, collaboration, and efficiency. Companies no longer need a separate content management system, training system, and QMS.

-Advanced application programming interface (API)-driven technology enables seamless external engagement with today’s growing pool of contractors to leverage their expertise. True cloud software allows the seamless interconnection between these contractors, service partners, and the organizations that they’re doing business with, and eliminates potentially risky manual hand-offs.

	Measure outcomes according to business values

	To build a convincing case for quality transformation, the quality organization must show how it is an important partner to the business rather than just a cost center. This can be an uphill battle, because many quality organizations are viewed as compliance-centric business units (i.e.,  part of  the cost of doing business). 

	To prove its value, the quality team must measure a quality transformation based on more than just compliance to also show how a transformation impacts patients and business operations.  PwC has identified the following as outcomes that impact business value:

	The return on investment for each quality outcome is measured by the business according to its impact on revenue, cost, inventory, and regulatory risk. Creating a framework within which to measure quality outcomes against these four parameters demonstrates the business value of the quality management transformation initiative. 

	For example, “competitive compliance” is a quality outcome that reduces costs and regulatory risk. This is made evident according to specific, related metrics, including audit and inspection observations, recall and deviation rates, and supplier risk profiles. 

	Another outcome, “improving speed to market”, increases revenue by reducing protocol amendment rates and serious breach and critical data error rates and increasing on-time post-approval changes. Yet another, “robust product and data,” can be measured by brand image, product release cycle time and variability, yield, and complaint rate. 

	Finally,“reliable supply,” which impacts both revenue and inventory, can be demonstrated with metrics. Examples would include service levels, shipping complaints, and adherence to manufacturing schedules.  

	One quality outcome has far-reaching implications: innovation. Quality organizations often overlook a number of ways that innovation can be improved. Each company will have a different set of metrics, depending on its level of technology maturity. The following are five areas where new technology can have a significant impact on life sciences innovation:

	Modernize manufacturing. The quality organization can play a major role in automating manufacturing processes. Quality organizations define how to provide feedback loops from laboratories back into the process. They look at how to leverage rapid micro techniques and electronic batch records.  These are innovations that can be measured.

 Emerging technologies (e.g.,  artificial intelligence and natural language processing or analytics) can be used to detect problems proactively. Quality teams can adopt these solutions to predict and prevent batch failures or to predict where the inspectors might find issues and resolve those issues beforehand.

 Unifying systems into one, integrated quality platform drives speed, agility, and visibility across the enterprise, creating measurable business value. This integrated system should also extend across the product lifecycle from research to distribution through commercial. It should also connect with clinical trial management and regulatory information management systems.

 Innovative quality solutions support, improve, and speed up clinical trials. Quality can play a significant role in developing more robust protocols which help reduce data error rates and even serious breaches, all of which accelerate reporting and the submission process.

Apply quality by design/quality risk management.

 Incorporating proactive approaches (e.g., quality by design [QbD], quality risk management [QRM], and continuous process verification [CPV]) help organizations speed up innovation. These techniques allow companies to focus their limited resources on the most critical items and that will make a positive impact on product quality and on patient wellbeing.   

	Translate value into bottom-line results

	While qualitative metrics can be used to assess value, executives also want to know the bottom-line impact of quality transformation on revenue, costs, inventory, and regulatory risks. Figure 2 shows the effects of a transformative QMS implementation on each of the main assessment areas. 

	The implementation of a cloud-based QMS can significantly impact revenues and costs by reducing the number of deviations, corrective action and preventive action (CAPAs), and recalls. With fewer investigations, companies can also reduce the resource burden in operations and quality assurance. The use of an innovative system with an automatic feedback loop also reduces the number of hours necessary for training, as well as the number of serious breaches, or protocol amendments that are required to improve yields. 

	New technology also impacts inventory and regulatory risks. Modern quality systems can reduce regulatory risk by identifying quality issues faster while at the same time reducing costs and total inventory. For example, by reducing the capital tied into the business and improving innovation around inline testing, or using more modern testing techniques, organizations can shorten cycle times across end-to-end product manufacturing to speed production and reduce inventory.

	For a multi-billion dollar company, just a 1% increase in revenue through improved quality can translate into millions of dollars in savings. For example, improving inventory turnover by 10% can free millions of dollars. Preparing an organization for quality transformation by looking at revenue, cost reduction, inventory reduction, and regulatory risk profile is critical to the business case. 

	Talk the language of executives to make a  business case

	Most executives do not speak the language of quality. For instance, they may not understand the impact of a deviation or a complaint, nor will they speak in those terms. Therefore, to demonstrate the value, quality teams need to talk the language of business.

	Every executive has slightly different priorities in addition to improving bottom-line revenue. Because each business area is different, it is important for quality professionals to consider how to speak with each member of the executive team, not only to get their buy-in to make the investment but to orchestrate and support the organizational change required for a quality transformation. 

	When talking to the chief operations officer, for instance, focus on the robustness of processes and products and improved cycle times. The chief financial officer (CFO) wants to know about the overall cost of quality, and the chief quality officer focuses on traditional compliance, so, when speaking to the them, change the conversation from dollars (which would be used with the CFO), to the impact of quality on business.  

	Think in terms of value, not just cost, about how a unified QMS can help improve revenue, reduce costs, lower inventory, and reduce regulatory risk. Moving to a unified solution is transformative and possible today. As more companies in the pharmaceutical industries to this successfully, Quality 4.0 may finally take hold in the life-sciences industry.  

	1. Juran Blog, LNS Research, “Quality 4.0: The Future of Quality?”

t: Partnering for Bio/Pharma Success
	February 2020
	Pages: 28–31

	When referring to this article, please cite it as M. Jovanis and J.P. Zonnenberg, "Building a Business Case for Quality Transformation," 

Pharmaceutical Technology Supplement: Partnering for Bio/Pharma Success

Articles

Quality/Regulations

Can the pharmaceutical industry embrace the goals of Quality 4.0?

Building a Business Case for Quality Management Transformation

The cell and gene therapy industry is at a major inflection point, as therapies move out of clinical trials and into the commercial market. As more therapies are commercialized and become established, demand for cell and gene therapies will grow, leading to vast changes in patient care. 

	Currently, dozens of products are already in Phase III, including second-generation cell and gene therapies such as CAR-T (chimeric antigen receptor T cells). Over the next 5–10 years, more than 70 cell and gene therapies are expected to be commercialized and available to patients. 

	Small and virtual biotechs are driving innovation in this sector, and make up over 85% of cell and gene therapy developers. Without the infrastructure of larger pharma & biotech companies, these smaller innovators face unique challenges in manufacturing these advanced therapies and ultimately bringing them to the market (1). The question for the industry and the contract development and manufacturing organizations (CDMOs) that support them is: “How do we robustly produce, ensure quality, and deliver these transformative and life-saving products to patients around the world safely?”

	As patient numbers addressable by cell and gene therapies grow, new technologies will be needed to meet manufacturing demands. Standardized and robust manufacturing platforms will need to be established, and a global network of facilities will be required to serve the main cell and gene therapy development hubs across the globe. 

	CDMOs are responsible not only for manufacturing drugs safely and robustly to meet customer demands, but also for supporting innovation from these small biotechs. This requires facilitating the delivery of therapies to the market under the right conditions, while accelerating an increase in overall capacity, and the infrastructure required to meet increased demand for these therapies at scale. For example, Lonza has been working with a small biotech that is innovating within the oncology and immune tolerance space. As their CDMO, we are committed to leverage our experience and expertise to de-risk their product’s pathway from lab to market and maximizing the product safety by industrializing its manufacturing process. 

	For any manufacturer, successful industrialization requires focus on the “cubic effect,” a concept to be discussed later in this article, which includes technical and operational development, as well as cost. 

	First, consider that cell and gene therapy is an ever evolving and complex science dealing with autologous and allogeneic cell therapies as well as viral vector gene therapies. There are variations in approaches to manufacturing between different therapies, and in the critical steps that surround streamlining and ensuring good process development. 

	However, when it comes to the regulatory pathway to scaling up processes and ensuring consistency, success depends on the manufacturing process and associated critical quality attributes. A fully optimized and robust process is needed, one that can be “mass customized” (i.e., for autologous therapies, for example, the process must be scaleable, reproducible, commercially viable, and customized for every single patient at a large scale). This is where CDMO experience and capabilities are most critical for customers who have been focusing on the safety and the efficacy of their therapy and now face an accelerated path to commercialization. 

	Reflecting on the difficulties of optimizing the process to ensure its scalability is the trouble that some innovators are currently experiencing in commercializing therapies. The importance of good process development is illustrated by the difficulty some therapies are encountering when moving to the commercial phase. Once approved, cell and gene therapies must comply with more stringent characteristics defined by regulatory bodies. Getting the process and the manufacturing approach right from the start can facilitate scale-up and reduce the risk of quality and consistency issues, which often result in delays due to the need to tweak processes at the critical commercialization point.

	Regulatory agencies are offering increased support to help advance the growth of innovative therapies that aim to meet unmet medical needs. Given the levels of efficacy that some cell and gene therapies have shown, FDA and other global regulators have created accelerated approval pathways and allowed unprecedented small-scale clinical trials for these therapies. Regulators are also supporting technologies that can advance manufacturing and shorten the timeline between clinical trials and commercial scale-up. 

	At this crucial point in the development of cell and gene therapies, developers need to constantly reassess the demand forecast and scale their production accordingly to ensure the right investments are made into CAPEX (capital expenditure) and OPEX (operating expense). Overestimating the figure will result in overcapacity in five or 10 years. This is particularly true since some of these therapies are curative and only administered to patients once, unlike treatments for chronic conditions, which require multiple doses or treatments over time. Once the current prevalent patient population is treated, the therapies would only be needed for newly diagnosed patients.

	The need for industrialization is not new for the life-sciences industry. In fact, with cell and gene therapies, we are seeing history repeating similar patterns that were seen in the past, when the first monoclonal antibodies (mAbs) and recombinant proteins were industrialized. While cell and gene therapy is much more complex, with autologous, viral, allogenic or in-vivo modalities, we would not be where we are today without the technological advancements of the past 30 years.

	Estimating infrastructure needs and achieving scale are not the only hurdles that cell and gene therapy developers now face. Success will also depend on reducing the cost of material goods for products, and maintaining consistent quality standards for the delivery of live biologic material within the stringent profile characteristics required for commercialization. 

	From manual processes to mass customization

	At this point, cell and gene therapy is still mainly driven by manual processes. Innovators will need to shift to a mindset based on mass customization. Every patient in the future will be different and will need to be treated in a different way. However, developers will have to produce a single, customized product with the same efficiency and quality used to mass-produce product.

	Having standardized processes in place will be a competitive differentiator for CDMOs that operate in the cell and gene therapy space. For example, autologous therapies will require disruptive solutions necessary to deliver on the promise of personalized medicines and move the industry from the standard of “one batch for many” to “one batch per patient.” For allogeneic therapies, CDMOs will look to leverage the expertise and experience acquired in large-scale manufacturing of biologics to drive the commercialization of these therapies, making them in a scalable manner so they can be available to large patient populations.

	In order to achieve these results, the industry as a whole must work together in a three dimensional “cubic effect” to drive improvements across:

	Although technology is important, improvements will be needed on the operational side. In order to deliver and treat patients in a more robust, safe, and cost-effective way, innovators and their contract partners will need to define and improve the way that they approach the following, in the cell and gene therapy space:

		Defining good takt time (i.e., the time between the start of production of one item and the start of production of the subsequent unit)

		Aligning operations to the shift in labor needs

		Defining operations that are in a closed system for efficacy and safety

	This shift in focus has already occurred in other aspects of life sciences, so we know that it can be applied to cell and gene therapy. Consider, for example, the fact that it used to cost more than $30,000 to manufacture just one gram of a standard mAb. Within two decades, CDMOs, working with innovators within the framework of the cubic effect, brought that cost down to under $10.

	In short, cell and gene therapy innovators and their contract partners need to focus on manufacturability and process industrialization as early in the development cycle as they can, to avoid a technical development bottleneck. Developers can greatly benefit from working with CDMOs, not only for traditional capacity but also to de-risk their path to commercial launch and to help them manage the unpredictability of demand associated with the curative nature of cell and gene therapies. Focusing on technical developments and the cubic effect must guide CDMOs as they work with smaller biotechs, who are at the heart of what the industry is trying to accomplish with meeting unmet medical needs.

	1. IQVIA Institute, “Emerging Biopharma’s Controbituion to Innovation: Assessing the Impact,” p. 13, June 2019.  

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	Supplement: Partnering for Bio/Pharma Successâ¨
	February 2020â¨
	Pages: 16–19

	When referring to this article, please cite it as A. Santagostino, "Using the 'Cubic Effect' to Drive Cell and Gene Therapy Commercialization," 

Manufacturing

Contract partners must help innovators, especially smaller and virtual companies, consider manufacturability as early as possible in development. This requires focusing on technical and operational performance, as well as cost. 

Using the ‘Cubic Effect’ to Drive Cell and Gene Therapy Commercialization

Pharmaceutical and biopharmaceutical companies have been extensively using contract research organizations (CROs) to meet their challenging needs in R&D and standard work for several decades. A noticeable shift occurred in outsourcing research and clinical work when Big Pharma R&D costs skyrocketed. For example, in 2012, approximately 33% of drugs in the pipelines of the top 10 pharmaceutical companies were initially developed elsewhere (1). 

	Sponsor companies engage CROs either on a transactional basis or on a strategic basis. In either case, stakes are high for pharmaceutical and biopharmaceutical companies to make sure CRO work is successful. Neither selecting a reputable CRO, micromanaging CRO work, nor throwing the work over the fence leads to a successful CRO relationship. Key strategies that can lead to a win-win relationship include a relationship on a solid foundation (CRO selection, quality management, and clarity in expectations), soft factors (build the trust and empowerment), and project management excellence (simplifying the complex, metrics, and continuous improvement). This article discusses these strategies as well as FDA guidelines on quality agreements for the contract manufacturing arrangements for drugs.

					The four commonly found “Cs” in contractual work are as follows:

	The strategies on win-win relationship were developed and implemented for CROs. The concepts, however, can be applicable to all outsourced contracting work with long-term strategies in mind.

	Transactional vs. strategic relationships

	Transactional relationships are favored for short duration and limited scope projects, (e.g., verification and validation studies and synthesis of organic compounds). Such a relationship merely augments the sponsor company’s internal resources during the crunch time. 

	Strategic relationship exists when sponsor and CRO actively work together to help each other achieve their respective objectives (2). Strategic relationships help both parties benefit from long-term commitments on infrastructure, continuous improvement, and innovations. The sponsor company is able to leverage in-house resources for business- critical projects. In addition, the sponsor company may realize opportunities to penetrate into a new market segment when the CRO is from a location where the sponsor company currently lacks any presence. 

	Typically, sponsor companies form strategic relationships with CROs to take care of standard work (e.g., on-going commercial stability studies, manufacturing of generics, compendial testing, remediation projects, and reference standards) and clinical studies. Examples of such strategic relationships include alliances of Syngene International with each of Amgen, Baxter Healthcare, Bristol-Myers Squibb, GSK, Herbalife, and Novartis, and that of Parexel with Eli Lilly.

	It is necessary to comply with FDA’s guidance document on quality agreements (3), which is a major step in an alliance formation. FDA’s regulations recognize that owners commonly use contract facilities to perform some drug manufacturing activities. Although the guidance is for CMOs, many of the principles described in this guidance could be applied in pre-commercial stages of the pharmaceutical lifecycle. Key highlights from the guidance document include:

		The owner’s quality unit is legally responsible for approving or rejecting drug products manufactured by the contract facility, including for final release. The quality unit’s responsibilities and procedures are required to be in writing and followed.

		Owners can use a comprehensive quality system model, in the form of a quality agreement, to help ensure compliance with cGMP.

		Owners are required to evaluate contract facilities to ensure cGMP compliance for specific operations.

		Key elements of the quality agreement include:

		Clearly described materials or services to be provided, quality specifications, and communication mechanisms between the owner and contract facility

		Explanation of how the CRO will report manufacturing deviations and how the deviations will be investigated, documented, and resolved in compliance with cGMP

		Definition of each party’s manufacturing activities in terms of how each will comply with cGMP. 

		It is recommended that quality agreements be separate documents, or at least severable, from commercial contracts such as master services agreements or supply agreements. Quality agreements may be reviewed during inspections.

		The buck stops with the sponsor. No matter who tests the products, the owners’ quality units are ultimately responsible for ensuring that the products are manufactured in accordance with cGMP. FDA could cite the owners for failing to evaluate, qualify, audit, and monitor their contract facilities.

		International Council for Harmonization (ICH) 

(4) states that, as part of a pharmaceutical quality system, the owner is ultimately responsible for ensuring that “processes are in place to assure the control of outsourced activities and quality of purchased materials.”

	The importance of a strong quality agreement was also emphasized in a CASSS organized chemistry, manufacturing, and controls strategy forum in 2014 (5).

	Key steps in the formation of a strategic alliance with a CRO are shown in 

. The win-win strategies can be grouped into three categories: strategies that can drive a solid foundation, soft factors, and excellence in project management (

Quality track record, firewall policies, depth and breadth of capabilities, resource pool in the local area, CRO financial situation, and the current management team are some of the important considerations in a CRO selection process. Clarity in statement of work (SOW) and work packages is of paramount importance to ensure a successful relationship. Meeting cadences and transparency at operational and management levels, feedback sessions, accountability on both sides, and an open-book work environment can lead to building trust. Steps such as coaching and mentoring CRO employees and providing them with a big picture can lead to a CRO feeling empowered. Finally, excellence in project management is also essential to a win-win relationship (e.g., templating standard work, acting on potential failure modes, strategic and tactical level metrics, and implementing Green Belt and LEAN projects to improve efficiency). Undoubtedly, the partnership will have to navigate through challenging situations. Illustrative scenarios describing issues and ways to resolve them are detailed in 

	It is often helpful to visualize how success and failure may look (

). A collaborative approach, instead of finger pointing and defensiveness, is evident in the successful alliance. A CRO is empowered instead of being micromanaged. Finally, continuous improvement tools are employed to improve efficiency in a successful CRO partnership.

	Partnerships with CROs can indeed deliver substantial benefits. However, a successful CRO relationship, even with a reputable CRO, is not a given. Beyond the obvious requirements, such as defining the outsourced work, due diligence in CRO selection, and the quality agreement, a significant investment of time and effort to build and maintain the CRO relationship is required to drive it to a success. By jointly following the strategies outlined in this article, the sponsor company and the CRO can maximize their odds of success.

	1.  J. Rockoff, “Pharmaceutical Scouts Seek New Star Drugs for Cancer, Diabetes,” 

, March 9, 2014.
	2.  J. Hughes and S. Price, “The Perils and Promise of Strategic Partnering with CROs,” 

Guidance for Industry, Contract Manufacturing Arrangements for Drugs: Quality Agreements 

(Rockville, MD, Nov. 2016).
	4.  ICH, Q10 Section 2.7, 

Management of Outsourced Activities and Purchased Materials

(2008).
	5.  A. Mire-Sluis et al., “Effective Management of Contract Organizations: Keeping the Product Pipeline Moving, Compliant, and Available,” 

	Shreekant Karmarkar, PhD, is president of DAT Pharma Consulting, Inc., 


	Supplement: Partnering for Bio/Pharma Success
	February 2020
	Pages: s20–s23

	When referring to this article, please cite it as S. Karmarkar, “Building Strategic Relationships with CROs,” in 

Outsourcing

How to adopt win-win strategies and understand quality agreements for complying with cGMP when building strategic relationships with pharmaceutical contract research organizations.

Building Strategic Relationships with CROs

Contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) continue to grow and expand to keep up with the latest advances and breakthroughs in services and technology for their clients. The following are some notable acquisitions, expansions, and industry partnerships that have occurred in recent months.

	Recipharm announced in November 2019 that it acquired Consort Medical, a drug delivery and device company headquartered in the United Kingdom, for £505 million (US$649 million) (1). Through the agreement, Recipharm will gain technological intellectual property along with access to new customers and Consort’s product portfolio from both of the company’s divisions, Bespak and Aesica. The acquisition is also expected to build up Recipharm’s scale and profitability with an annual pro forma revenue of SEK 10,847 million (US$1.1 billion) and pro forma earnings before interest, tax, depreciation, and amortization of SEK 1793 million (US$186 million).

	On Dec. 4, 2019, Cambrex Corporation announced its sale to an affiliate of the Permira funds had been completed. The acquisition agreement was valued at approximately $2.4 billion (2).

	In a press release, Cambrex said the investment “will support the ongoing growth of Cambrex’s integrated services offering by enhancing the company’s ability to service its global customer base, and broadening its capabilities to provide additional world-class services to support the analysis, development and manufacturing-from preclinical through commercial phases-of drug substances and products.”

	“The completion of this transaction kicks off the next exciting phase of growth for our company,” said Steve Klosk, president and CEO of Cambrex in the press release. “We look forward to working with the Permira team to further enhance our best-in-class capabilities, strengthen our market-leading position, and broaden and deepen our customer relationships.”

	Catalent announced it completed the purchase of Bristol-Myers Squibb’s biologics, sterile, and oral solid dose product manufacturing and packaging facility in Anagni, Italy in January 2020 (3). The 28,000-square-meter (305,000-square-foot) facility offers aseptic liquid and powder filling for biologics and sterile products for multiple vial sizes, and primary and secondary packaging solutions, including serialization, to support product launches for oral solids, sterile, and biologics products. Catalent has also revealed that it plans to make further investments in the site’s growth, the company said in a press release.

	“The Anagni facility supplements our European commercial supply capabilities and will integrate well with our existing global early development and clinical supply sites to smooth the transition from development to commercial supply,” said Alessandro Maselli, Catalent’s president and chief operating officer in the press statement. “Anagni provides our European customers with great biologics and oral dose capabilities that can help us reduce time-to-market, simplify tech transfers, and minimize program risk.”

	Additionally, Catalent announced it was investing $9 million into a new clinical supply facility in San Diego, CA that will begin operations in the summer of 2020 (4). According to a Sept. 5, 2019 press release, the new facility will provide clinical supply services to pharmaceutical and biopharmaceutical customers and will specialize in services for early phase clinical trials while enhancing the company’s OptiForm Total Supply service, which offers customers integrated development, clinical supply manufacturing, and distribution. The facility will also handle clinical supply management, primary and secondary packaging, complex labeling services, clinical storage, distribution, and drug returns and destruction and will include stability chambers.

	In early 2020, WuXi STA, a subsidiary of WuXi AppTec, announced the opening of its new large-scale oligonucleotide API manufacturing facility in Changzhou, China (5). At 30,000 square feet, the new site can manufacture oligonucleotide APIs up to 1 mol/synthesis run, which will further expand the company’s ability to deliver new oligonucleotide therapies to market, according to a company press release. The facility can also provide services for small molecules, peptide process R&D, and manufacturing from laboratory to commercial scales.

	“By leveraging our small-molecule CMC (chemical, manufacturing, and control) technology and capability platform as well as global standard quality system, WuXi STA provides a robust one-stop shop for oligonucleotide innovators. The opening of this large-scale manufacturing facility will empower more global partners to expedite the development and commercialization of oligonucleotide drugs to benefit patients worldwide,” said Dr. Minzhang Chen, CEO of WuXi STA, in the press release.

	PCI Pharma Services announced a facility expansion at its Tredegar facility in Wales, UK and a facility expansion completion at its Rockford, IL, facility in December 2019. The Tredegar facility is set to be completed by late 2021, and the expansion will double the facility’s large-scale granulation and fluid bed drying capacity, create additional space for new potent handling capabilities, and will add an analytical and a small-scale processing area for early stage non-good manufacturing practice (GMP) processing and formulation, according to a company press release (6).

	After the expansion, the Rockland site is now the largest of the company’s eight locations and features four high-potent-compound-capable suites built to International Organization for Standardization (ISO) 8 standards, high-efficiency particle air filtration technology, three new secondary packaging areas, and three new coolers and a new freezer for 20 °C to -8 °C cold-chain requirements (7).

	“Across the globe, we are making strategic decisions that enable us to continue to support our clients’ business and meet increased demands for our integrated services,” said Salim Haffar, CEO, PCI Pharma Services, in a press release.

	On Jan. 22, 2020, The Discovery Labs, an MLP Venture company and provider of cGMP manufacturing, turnkey laboratory solutions, critical materials, and office space, and Deerfield Management, a healthcare investment management firm, announced that they have formed The Center for Breakthrough Medicines, a new contract development and manufacturing organization (CDMO) and specialty investment company (8). Under the new CDMO, the companies will invest $1.1 billion to build a manufacturing facility for cell and gene therapies.

	“The Center for Breakthrough Medicines will be serving companies from the earliest stages through commercialization. Its exceptional scale and offering will quickly relieve the production bottleneck for advanced therapies by reducing the time, complexity, and cost of commercializing vitally needed gene and cell therapies,” noted Audrey Greenberg, board member and executive managing director for The Discovery Labs, in a company press release.

	Lonza revealed in October 2019 that it was extending its partnership with Genmab, a Denmark-based biotechnology company specializing in antibody therapeutics for cancer, to cover preclinical and clinical development and manufacturing for a significant portion of Genmab’s pipeline (9). The companies have been in collaboration since 2002.

	The agreement aims to provide Genmab with security of supply and to enable Genmab to move rapidly into clinical manufacturing with the flexibility needed to manage an extensive pipeline through the demands of clinical trials. It will also include developing complex molecular formats using Genmab’s DuoBody technology.

	Lonza also entered into a partnership with Cryoport in November 2019 to strengthen its ‘vein-to-vein’ delivery network by removing supply chain hurdles faced by developers of personalized therapeutics (10). The new collaboration will aim to provide fully integrated solutions, including co-location of manufacturing bioservices and distribution facilities, automated data management, and process optimization.

	“The Lonza-Cryoport collaboration is an enabling part of a wider goal for Lonza to create a network of strategic partnerships and capabilities that enable seamless vein-to-vein delivery of cell and gene therapies for its customers and their patients,” said Alberto Santagostino, SVP head of Cell & Gene Technologies, Lonza Pharma & Biotech, in a press release. “There is no doubt that this partnership enables us to provide a best-in-class solution to cell and gene therapy companies for manufacturing and supply chain services, allowing us to provide a fully integrated solution that reduces risk and increases transparency.”

	In September 2019, Catalent entered into a long-term commercial supply agreement with Minerva Neurosciences, a Waltham, MA-based biopharmaceutical company focused on the development of therapies to treat central nervous system (CNS) disorders (11). The collaborations will center on roluperidone (MIN-101), an investigational compound under development by Minerva, for the treatment of negative symptoms of schizophrenia. If its successful in Phase III clinical trials, the drug will be the first treatment approved to treat symptoms of schizophrenia in the United States, according to the companies.

	Catalent announced two additional partnerships in December 2019, one with Ethicann Pharmaceuticals for the development of a new combination pharmaceutical-grade cannabidiol and tetrahydricannabinol product to treat multiple sclerosis (12), and one with Bridge Therapeutics for the formulation, development, and production of BT-219, a new opioid addiction treatment (13). Both drugs will be used with Catalent’s Zydis orally disintegrating tablet technology.

	“The Zydis technology platform has been shown to be very versatile and effective in developing easy-to-administer dose forms for innovators and to date, more than 36 products have been launched using Zydis technology in over 60 countries,” said Jonathan Arnold, president of Catalent’s Oral and Specialty Delivery business unit, in a press release.

	Samsung Biologics announced a long-term agreement with Ichnos Sciences, a Paramus, NJ-based biotech company, in November 2019 for the manufacturing of drug substance for ISB 830, an anti-OX40 monoclonal antibody in development as a potential treatment for moderate-to-severe atopic dermatitis (14). Through the agreement, Samsung will provide flexible business terms while offering full regulatory support and improved batch release from small to large scale, according to Samsung.

	1. Recipharm, “Recipharm Offers to Acquire Consort Medical to Become a Leading Inhalation Company and Top Five Global CDMO Player,” Press Release, Nov. 18, 2019.
	2. Cambrex, “Cambrex Announces Completion of Acquisition by the Permira Funds” Press Release, Dec. 4, 2019.
	3. Catalent, “Catalent Completes Purchase of Biologics Fill-Finish and Oral Solid Dose Facility in Anagni, Italy,” Press Release, Jan. 7, 2020.
	4. Catalent, “Catalent To Open New Clinical Supply Facility in San Diego,” Press Release, Sept. 5, 2019.
	5. WuXi STA, “WuXi STA Opens Oligonucleotide Large-Scale Manufacturing Facility,” Press Release, Jan. 3, 2020.
	6. PCI, “PCI Pharma Services Announces UK Facility Expansion,” Press Release, Dec.17, 2019.
	7. PCI, “PCI Expands Illinois Pharmaceutical Manufacturing Facility,” Press Release, Dec. 6, 2019.
	8. The Discovery Labs, “The Center for Breakthrough Medicines is Building the World’s Largest Cell and Gene Therapy Contract Development and Manufacturing Organization (CDMO) to Launch in King of Prussia, PA,” Press Release, Jan. 23, 2020.
	9. Lonza, “Lonza’s Ibex Solutions to Support Genmab’s Growing Clinical Portfolio,” Press Release, Oct. 14, 2019.
	10. Lonza, “Lonza Partners with Cryoport and Strengthens its ‘Vein-to-vein’ Delivery Network in Cell & Gene Therapy,”  Press Release, Nov. 5, 2019.
	11. Catalent, “Catalent and Minerva Neurosciences Enter Commercial Supply Agreement for Schizophrenia Drug Roluperidone,” Press Release, Sept. 24, 2019.
	12. Catalent, “Catalent to Partner with Ethicann on New Fast-Dissolve Cannabinoid-Based Treatment for Multiple Sclerosis Spasticity,” Press Release, Dec. 3, 2019.
	13. Catalent, “Catalent Partners with Bridge Therapeutics on Formulation, Development and Production of New Opioid Addiction Treatment,” Press Release, Dec. 10, 2019.
	14. Samsung Biologics, “Samsung Biologics and Ichnos Sciences Announce Agreement for Manufacture of ISB 830,” Press Release, Nov. 5, 2019.


	Supplement: Partnering for Bio/Pharma Success
	February 2020
	Pages: s32–s34

	When referring to this article, please cite it as, “Pharma Contract Market Update," 

Pharmaceutical Technology Partnering for Bio/Pharma Success

CMOs and CDMOs expanded their services and facilities in 2019 and early 2020.

Pharma Contract Market Update

New technologies and digital trends continue to drive growth in the possibilities associated with digitalization. As one of the world’s most highly regulated industries, the pharmaceutical industry is diverse and complex. That is why digitalizationin the pharmaceutical industry as compared to other industries began at a later date. And, while the challenges of digitalization within the pharmaceutical industry are similar between different players (i.e., contract manufacturing organizations and marketing authorization holders), there are some special challenges that a contract development manufacturing organization (CDMO) must contend with. What are these challenges and how does a CDMO approach digitalization in general? Consider the following best practices for digitalization for CDMOs.

	A significant benefit of digitalization in the pharmaceutical industry is making documentation processes both safer and more efficient. Although CDMOs by their very nature differ from their pharmaceutical and biotech customers, these differences can be more noticeable when it comes to digitalization. Laboratory testing equipment is one such example because customers, not the CDMO, determine what testing equipment is to be used for a particular analysis. A drug producer can use one type of equipment, but for a CDMO it may be that many different types of equipment are needed for the same kind of testing depending on the customers’ choice. The resulting variety of details in the test methods make the digital connection and the design of digital processes more challenging. Furthermore, aCDMO usually has a heterogeneous customer base with diverse products, which leads to a multitude of process variants, such as varying documentation processes. A one-to-one adoption of this variety of paper-based documentation processes in the digital system would lead to a high maintenance effort and thus loss of efficiency. Therefore, it is important to harmonize and standardize the processes in order to digitalize them using software.

	Digitalization usually doesn’t take place in one single project; it is rather approached as a comprehensive program containing several sub-projects. When it comes to processes, these sub-projects often depend on each other and have some correlations. For this reason, it is important to determine if there are dependencies between the projects or even possible synergies. The digitalization of a process could well affect other projects. Additionally, determining business process ownership may not be as transparent as one might hope. As such, it is important to identify cross-divisional processes and define their ownership in order to sucessfully digitalize them.

	While standardization can help a CDMO to reduce overall process complexity, it is crucial that flexibility be maintained to fulfill individual customers' needs. Paper-based processes can be flexible (e.g., when handling different filling processes based upon a customer’s requirements), but the use of a digital system might affect flexibility because it aims to standardize processes in order to handle them in the system. For example, a CDMO’s customers use different wordings in their production specifications. If not standardized, the different wordings result in multiple process variants that would need to be reflected in the digital system. In this case, the use of predefined text modules that cover all important aspects would meet both standardization and flexibility. Digitalization itself will not prevent a CDMO from remaining flexible, but the aspect of flexibility should be considered in the design of the systems.

	The technical and process elements of digitalization are important aspects to be considered within the organization, but these are only one side of the coin. Today, technologies are part of our daily lives, and the transformation within an organization that comes with digitalization affects personnel. The organizational culture itself is a system of shared beliefs and attitudes that develop over time within an organization. Thus, when the process is not well explained to staff or the fear of using a new modern technology is not taken seriously, acceptance of the new system can be low. Different educational levels of staff, generation gaps, and even vision and corporate mission statements can all affect transformational management. Therefore, the key for many organizations is how to maintain a smoothly functioning culture and workplace when the workplace itself changes. 

	When it comes to accepting and using digitalization, staff can be divided into digital or non-digital natives. There may be other categories of stakeholders that should be considered as well, including management, affected employees, workers’ council, as well as both supporters and detractors of the project. A sophisticated stakeholder analysis is key to creating dedicated and effective transformation activities. It is advisable that organizations create a dedicated transformation team at an early stage, ideally incorporated into the corporate strategy. 

	Digitalization as a term has a broad spectrum and can take place within many different parts of a CDMO. While Industry 4.0 is production oriented, there are different digitalization projects that are not directly associated with the value chain, such as data analytics software in the field of R&D. It is important to segment the topic of digitalization into different groups to get a proper overview. For example, digitalization can be as simple as replacing a paper book at a visual inspection workstation with a tablet. Staff members would enter their inspection findings directly into the enterprise resource planning system using the tablet instead of documenting them in a paper book.  

	The process could also be more complex, such as digitally designing formerly paper-based processes within a new software. For example,the transfer of measured data in a laboratory previously taking place in an analog manner could be connected to a digital process. The measuring equipment would automatically send the data to the software, which stores it and processes the data for downstream steps. Digitalization also covers new trends and technologies such as machine learning, artifical intelligence, blockchain, and big data. And while there is significant potential in these technologies, it is best to use them only where they make the most sense. Projects should be chosen independently from their duration and complexity, focusing instead on whether the project will increase quality and efficiency and, thus, add value to the organization and all related partners, including customers and suppliers. 

	When it comes to digitalization, pharmaceutical companies and CDMOs have a lot in common. A clear focus on projects that add value as well as managing organizational and technological change are only two examples. However, the high complexity due to the high process variety as well as the digitalization of processes while maintaining flexibility are specific challenges of a CDMO. Having the expertise necessary to deal with these challenges is crucial for a CDMO. Done right, digitalization has a positive impact on the quality of products and processes of a CDMO, and a customer-centric and innovative approach maintains its flexibility.

					Consider the following key points when approaching digitalization as a CDMO:

	Kai Vogt is senior vice-president Corporate Development, Legal and Compliance, Information Technology at Vetter Pharma. 


		Supplement: Partnering for Bio/Pharma Success
		February 2020
		Pages: s24–s26

		When referring to this article, please cite it as K. Vogt, “Digitalization: A CDMO’s Perspective,” in 

Pharmaceutical Technology Supplement: Partnering for Bio/Pharma Success

CDMOs must consider challenges associated with the complexity of contract pharmaceutical manufacturing when approaching digitalization projects. 

Digitalization: A CDMO’s Perspective

As cell and gene therapies are garnering more interest within the biopharma industry, demand for adequate manufacturing capacity and talent to ensure success is increasing. To explore how outsourcing can prove beneficial for cell and gene therapy (CGT) development, Pharmaceutical Technology spoke with Miguel Forte, chief commercialization officer, ISCT, CEO of Bone Therapeutics, and former CEO of Zelluna Immunotherapy; Alengo Nyamay’antu, scientific communications manager, Polyplus-transfection; and Matthew Lakelin, vice-president business development and scientific affairs, TrakCel.

 What are the key benefits of partnering with an outsourcing organization for the development of CGT?

 Outsourcing is a key element of any biotech business and virtually a requirement to be able to expand and reach out to needed competencies and resource management. For any biotech, and in particular for CGT highly innovative processes, the use of outsourcing enables companies to take advantage of additional required competencies. Even though the ownership of intellectual property (IP), know-how and processes, and data should always remain with the CGT companies, the ability to use outsourced competencies, in a field where not enough talent is available, is a very important success factor. In addition, outsourcing enables organizations to manage their cash flow. 

	One example is manufacturing, where the use of contract development and manufacturing organizations (CDMOs) provides not only additional competencies but a de-risking of the investment. At early stages of still invalidated technologies or products, it may be of significant risk to establish large ‘in-house’ structures that carry significant cost associated with the risk. An outsourced investment enables the product developing companies to progress with the technology at reduced risk with cash flow management. 

: CGT developers are booming and viral vector large-scale manufacturing is short of capacity. The majority of developers from small biotechs and even from Big Pharma rely on outsourcing partners, including contract manufacturing organizations (CMOs, CDMOs) with extensive experience to accelerate the journey of their drug product from bench to market. This choice is governed by the fact that significant capital investments are necessary to build dedicated viral vector manufacturing facilities for commercialization, as well as require manufacturing and regulatory expertise to upscale manufacturing in compliance with good manufacturing practices (GMP) guidelines. Outsourcing partners put forward their process development know-how to meet the needs of developers. They usually put forward the flexibility and adaptability of their viral vector manufacturing platform: adherent or suspensions cell culture systems, established process development for various viral vectors, and scalability of production for pre-clinical to commercial product supply.

 There are a number of benefits to outsourcing the development of advanced therapy medicinal products (ATMPs), and we continue to see outsourcing of key processes taking place. One reason for this is the shortage of manufacturing facilities available to the sponsor. While we see a number of biotech’s investing in in-house manufacturing facilities, there are many that opt to use CDMOs to assist in the manufacturing stage of product development. As a result, outsourcing can provide benefits that include quality, efficiency, productivity, and a quicker ‘time-to-market’.

 Could you highlight some of the challenges facing outsourcing partners to be able to effectively meet the demands of CGT development?

 CGT developers rely on contract manufacturers to produce their therapeutic viral vectors at a larger scale with quality, reliability, and efficiency. One specific challenge that an outsourcing partner needs to address and that impacts all of the aforementioned requirements is supply of raw materials. Production of therapeutic viral vectors is dependent on a great number of complex and specialized raw materials, of which cell culture media, cell lines, plasmid DNA, and transfection reagent are particularly important.

The products that we see day-to-day have very different supply cycles and different challenges associated with them to more traditional therapies. For autologous therapies, there are certain requirements of the treatment process such as Chain of Custody (CoC) and Chain of Identity (CoI) that must be adhered to that can present challenges. The personalized nature of these therapies relies upon the ability to track and identify product as it moves through the circular supply cycle and back into the patient. In addition to these challenges, we believe that manufacturing cost of goods is an issue that the industry is trying to reduce. 

 The most important factor in the success of an outsourcing partnership rests on the cultural fit of both organizations. It is crucial that the outsourcing organization understands, adapts, and responds to the size, needs, and strategic growth of the in-sourcing partner. The partnership needs to operate in a clear team spirit even though the roles and responsibilities are defined and well respected. An efficient and adapted way of working together is critical for success.

	Clearly the outsourcing partner has to have the right competencies and talent to provide the required services. This requires access to talent, which may prove a challenge in view of the limited availability of trained talent in the CGT field. Leading organizations in the sector are making conscious efforts to provide training and an ‘educating home’ to raise the availability of required talent.

	Different sources of outsourcing services also require access to state-of-the-art technology and equipment, which frequently is owned and managed in between both in-sourcing and out-sourcing organizations.

	Finally, there are the challenges in the field, in general namely regarding clinical development and clinical trials implementation, regulatory, market access, and physician and patient information and awareness.

 Within the context of manufacturing, more and more investment is being made into manufacturing technologies, particularly the aspect of automation, in an effort to drive efficiencies and lower cost of goods. Automation can help to lower cost of goods by reducing the amount of manual labor required while maintaining GMP. Manufacturing technologies are certainly moving toward this direction, bringing the benefit of reduced labor but also fewer ‘open steps’ in manufacturing, leading to a reduction in time from starting material collection to product administration. With regards to addressing the needs for CoI and CoC in the supply cycle, more and more developers are choosing digital, cloud-based system to provide visibility and compliance in the delivery of their product.

 These challenges are being addressed individually by the different organizations or generally throughout the field under the guidance of leadership organizations that aim at promoting the development of new CGT products for the benefit of patients with unmet medical needs.

	Within the role of individual organizations, an important consideration to enable success is the selection of an outsourcing partner. Through analysis of the required capabilities and competencies is the first step since the availability of ‘hard skills’ is obviously a must. The cultural fit and the assessment of the outsourcing organization ‘soft skills’ is also an absolute must. The selection process should be thorough and documented even before financial aspects are considered.

	The challenge of scarcity of talent, both within product developing organizations as well as within CDMOs, is one that with the clear expansion of the field represents a significant challenge. Correct search and attractive projects will help ensure adequate staffing of outsourcing partners. Leading organizations in the field of CGT are actively contributing to the training and networking of emerging talent.

	It should also be pointed that in the face of growing evidence of significant and long-term value, CGT products are delivering to patients, the general challenges regarding the full chain of value from innovation to market access are being addressed by multiple stakeholders and regulators are becoming more familiar with this field and more willing to take risks in favor of the value these products are delivering to patients.

 Developers are dependent on manufacturers who are themselves dependent on suppliers of raw materials. The selection of raw material suppliers by developers and manufacturers is important to anticipate future needs during scaling up and commercialization. Raw materials will need to be GMP-compliant for the drug product to reach commercialization, and their supply should be secured. 

Do you have any experiences of the issue of a lack in manufacturing capacity for CGT?

 It is clear that with the growth of the field with multiple products in development and an expanding number of organizations involved in CGT product development, the demand for outsourcing partnerships is increasing and the availability is somewhat limited. Some areas represent a bigger challenge than others, specifically gene editing, viral vectors, or manufacturing, while availability is bigger in other areas, such as clinical research organizations and clinical development, where the challenge is to select an adequate and relevant partner for your project.

	It is critical to anticipate needs as part of well-controlled project management approach for the development of a product. Anticipating when the outsourcing needs are going to be required allows for adequate selection and availability programming and, to a certain extent, absorb any potential waiting times in a parallel project management approach.

	At the same time, and in view of the success of the field again delivering value to patients and expanding business opportunities, industry is also witnessing an expansion in the availability of outsourcing partners, with more and more flexible and competent CDMOs and other provider organizations being created, which can offer support and availability for outsourcing partnerships.  

 Due to the rapid growth and potential of the personalized medicine market over the past decade, there have been a number of factors that have arisen regarding the capacities of outsourcing partners. Sourcing, harvesting, and transporting materials through the supply chain can be a real challenge, and as a result we have seen a number of innovative new companies formed to address these pain points. Many companies across different functions are working together to address the challenges in the delivery of these therapies from cryopreservation logistics through to patient support services. It is this collaboration between outsourcing partners that is addressing some of the challenges. 

 What advice would you give companies seeking an outsourcing partner for CGT development?

 It goes without saying that a demonstration of good practices is essential when considering outsourcing activities in ATMP development. Regulatory requirements often set the starting point in a vendor selection process. Additionally, it is certainly advisable for companies to select an outsourcing partner that can demonstrate a good understanding of technology transfer. Each manufacturing process is bespoke with CGT, so the ability to execute often complex manufacturing cycles is essential.

 The introduction of any starting or raw/ancillary material in the manufacturing process of viral vectors is a risk in itself. It is therefore essential for companies to judicially choose outsourcing partners that evaluate each raw material individually through a risk-based approach. To mitigate risks, more and more outsourcing partners are choosing to use essentially GMP-compliant raw material. Manufacturing GMP-grade raw materials ensures that the manufacturing process has been validated. As such, companies can be confident that quality and safety are ensured to meet regulatory agencies requirements.

 The first aspect is for the companies to know and own their technology, process, and product. This is critical for the success and control of your product development and business viability. Second, the correct selection of your partners is vital, both on the competencies and ‘hard skills’ aspect but also on the aspect of cultural fit and ‘soft skills’. This will ensure adequate technical performance and good team collaborative working spirit to face the development challenges and tight timelines. Make sure there is good integration between organizations and a good project management. This aspect is also of vital importance for success.

	One additional aspect to be considered in outsourcing partnering is risk-sharing. In some circumstances, particularly in early stages with low cash flow but high potential projects, the in-sourcing organization, and the outsourcing organizations may benefit by sharing the costs, the risk, and, consequently, the returns on the project. This may make financial sense, enable a short-term project, and solidify the partnership.

	Finally, make sure your organizations, both the insourcing and the outsourcing, engage in constant training, update, exchange of information, and experience through the network. 

 What trends do you predict will impact outsourcing within CGT in the coming decade?

 I believe there will be an increase in outsourcing as organizations, particularly start-up companies, will be more virtual and take advantage of providers with knowledge and the technical and financial ability to conduct the activities needed for those companies. It makes clear sense to own the technology and the know-how but take advantage of the flexibility and financial advantages of outsourcing.

	Providers will expand and deliver services that will be both broad as well as specialized but covering a wide range of offerings. Only very large organizations will keep most of the functions in-house and even these will take advantage of the availability of expert focused capabilities that can deliver services flexibly and cost-effectively.

 I would anticipate continued innovation in manufacturing technologies. Automation has been demonstrated to show benefits in the manufacturing process already, and there is certainly more and more interest in emerging technology areas such as big data and artificial intelligence. 

	Furthermore, I would expect to see a move towards standardization within the CGT industry. By establishing more consistent practices across manufacturing, logistics, compliance, and many other areas, the industry will be able to overcome some of the current growing pains it is experiencing. The ability to harmonize many of these components will push the industry forward and more importantly, get the right treatments to the right patients globally.


	Supplement: Partnering for Bio/Pharma Success
	February 2020
	Pages: s10–s15

	When referring to this article, please cite it as, “Sourcing Success in Cell and Gene Therapy Development," 

Development

As cell and gene therapies become more prominent, industry is seeking the expertise and capabilities of outsourcing partners to ensure success.

Sourcing Success in Cell and Gene Therapy Development

	Emerging therapies are testing the capabilities of biologic drug manufacturing companies, as well as contract development and manufacturing organizations (CDMOs) and contract manufacturing organizations (CMOs). As a result, these manufacturers are employing process optimization and scalable advanced technologies to produce more product in less floor space.

	“To respond to market needs for capacity, speed to manufacturing, modular platforms, and workforce training are at the forefront of any business strategy,” says Michelle Stafford, global marketing leader, BioProcess Solutions, GE Healthcare Life Sciences. “Speed to manufacturing can include in-sourcing/outsourcing analysis, which will take into account the long-term business plan, [intellectual property] IP protection, capital expenditures, time to market, and the technical capabilities of manufacturing or CDMO personnel. The result of this analysis will determine if capacity is outsourced to a CDMO or organic expansion and training is warranted.”

	“For mammalian manufacturing, there have been significant expansions in CMO/CDMO capacity over the past year with many companies announcing new facilities,” explains Charles Christy, head of commercial solutions, Ibex Dedicate, Lonza Pharma & Biotech. “Single-use technology is facilitating rapid addition of capacity, and process intensification is also playing a role in optimizing existing assets.”

	CDMOs have stepped up investments in cell therapy and gene therapy capabilities to secure a share of this market and to foster small biotechs in advancing prospective therapies. Most notably, in the first half of 2019, Thermo Fisher Scientific acquired Brammer Bio for $1.7 billion and Catalent purchased Paragon Bioservices for $1.2 billion, giving the CDMO giants capacity in viral-vector manufacturing.

	While this consolidation means there are fewer competitors in the market, industry experts see benefits including standardization of methods, simplified vendor management, and use of advanced technologies.

	“CMOs not only provide manufacturing capacity on the traditional side, but also build the capacity for novel modalities,” says Andrew Bulpin, head of process solutions, MilliporeSigma. “This enables small and virtual companies to stay independent longer.”

The need for manufacturing speed inspires contract manufacturers to explore advanced processing technologies.

Pharmaceutical Technology-02-01-2020

Building a Business Case for Quality Management Transformation

Using the ‘Cubic Effect’ to Drive Cell and Gene Therapy Commercialization

Building Strategic Relationships with CROs

Pharma Contract Market Update

Digitalization: A CDMO’s Perspective

Sourcing Success in Cell and Gene Therapy Development

More Capacity and Technology Translate to More Options

Growth in Biologics Market Inspires Outsourcing

Pharmaceutical Technology North America, Partnering for Bio/Pharma Success 2020 Supplement (PDF)