With today’s growing pipeline of biologics, namely complex oncology products often delivered parenterally, and COVID vaccine production, there is increasing demand for technically advanced manufacturing support, in which contract development and manufacturing organizations (CDMOs) are playing a vital role. Biologics require special procedures and equipment for fill finish operations to ensure product quality and safety, giving rise to the need for flexible aseptic fill finish technologies. With biologics representing a majority of top-selling drugs and the fastest-growing pharmaceutical segment, there is a growing strategic role for CDMOs that specialize in aseptic fill finish for injectable medications. This article offers insights into the parenteral and fill finish manufacturing markets, opportunities, and recent investments in the space.

Parenterals are sterile preparations containing one or more active ingredients for administration by injection or infusion. Parenteral administration is the prominent route, allowing direct administration of drug substances and to ensure bioavailability. Growth in the development of parenteral drugs is driving demand for advanced drug delivery devices such as prefilled syringes, another growing segment in the fill-finish manufacturing market.

According to a market research report by Fact.MR, “Parenteral Drugs Market Forecast, Trend Analysis & Competition Tracking – Global Market Insights 2019 to 2029,” the parenteral drugs market is poised to reach a staggering valuation of $802 billion by the end of the forecast period.¹ The report attributes this to increased spending on biologics, the need for faster route of drug administration, increasing preference for single dose administration of vaccines and drugs, and increasing numbers of local manufacturers.¹

There were close to 500 parenteral drugs in the pipeline as of 2018 and the proportion of which requiring parenteral administration rose by ~2% from 2018 to 2019, according to the Fact.MR report. Also, according to the report, monoclonal antibodies (mAb) led the global market, contributing a revenue share of 20% in 2018.¹

Market Trends
Following upstream bioprocessing and taking place after downstream purification, fill-finish is the final and most critical step in the drug manufacturing process and involves aseptic filling of biologic drugs or medicines, such as sterile liquid, powder, and suspension, in vials, ampoules, bottles syringes, and cartridges. The fill finish manufacturing market was valued at $6.1 billion in 2019 and is projected to reach $12.5 billion by 2027, and is expected to grow at a CAGR of 9.6% from 2020 to 2027, according to a study by The Insight Partners, “Fill Finish Manufacturing Market Forecast to 2027 – COVID-19 Impact and Global Analysis – By Product, End User.”² The adoption of prefilled syringes for parenteral administration and increased demand for biologics is driving the market.

Furthermore, according to The Insight Partners new research study, “Pharmaceutical Fill and Finish Outsourcing Market Forecast to 2028 – COVID-19 Impact and Global Analysis By State of Finished Products (Solids, Semi-Solids, and Liquids) and Content,” the pharmaceutical fill and finish outsourcing market size is projected to reach $4.0 billion by 2028 from $2.7 billion in 2021, and is expected to register a CAGR of 6.1% from 2021 to 2028.³

Carsten Press, Senior Vice President Key Account Management, Supply Chain Management, Marketing at Vetter Pharma International GmbH, said, “Today’s global pipeline is dominated by complex oncology products, while sales of rare disease treatments are predicted to double by 2026 – to up to $268 billion.⁴ Often based on highly sensitive molecules and delivered parenterally, these new products have fueled surging demand for technically sophisticated manufacturing support. This trend has also resulted in a growing strategic role for CDMOs that specialize in aseptic fill-finish for injectable medications – a domain that shows signs of unwavering strength. The market for parenteral drugs is expected to grow to $1 trillion by 2026, with biologics taking over the segment’s top 10 best-selling molecules.”⁴

Press added, “An increasingly important source of both these new products and opportunities is China. While North American markets will continue to drive sales of parenteral medications, the fast-growing Chinese biopharma sector represents a major volume opportunity. This key Asian market is rapidly pivoting away from me-too products and toward innovation,⁵ a transition that’s driving a surge in demand for manufacturing partners with the expertise and networks Chinese companies need to scale and expand internationally. For expert CDMOs, this trend will make China tremendously interesting for any long-term growth strategy.”

With pharma and biopharma companies increasingly focusing program development and manufacturing in the primary markets of the U.S. and EU, Mike Babics, Vice President, Parenteral Services, Alcami, said, “Alcami and other top five most active global sterile drug product contract manufacturers based in the U.S. and EU have been significantly investing in expanding isolator-based fill-finish capacity for both vials (lyo & liquid) and syringes. These investments have been needed to meet the rapidly growing demand for parenteral products and the intensifying regulatory expectations that all sterile manufacturing lines will utilize isolator technology to minimize potential risk to patient safety from the manufacturing process.”

According to Babics, the five most active sterile drug product contract manufacturing organizations (CMOs), along with Alcami, each manufacture more than 20-plus global commercial products for a variety of clients, along with dozens of clinical programs annually. “Alcami alone anticipates helping clients launch two to three commercial products annually, across a variety of formats. All of the leading parenteral CMO’s also have capabilities for liquid vials, lyo vials, and liquid pre-filled syringes (PFS),” said Babics.

Additionally, as pharma and biopharma portfolios increasingly focus on rare and ultra-rare indications, there is increased pressure from the accelerated timelines under expedited program reviews, Babics noted. “To expedite timelines, they purposefully seek out CDMO partners that offer extensive formulation and analytical method development, which can be rapidly transferred into non-GMP batches for toxicology material followed by GMP manufacturing,” said Babics.

COVID Impact
The impact of the COVID-19 pandemic on the industry is not only driving demand for capacity and capabilities but underscores the importance of relationships. CDMOs are adapting to the current manufacturing environment for parenterals and demand driven by COVID vaccines, doing what they do best—providing flexibility.

Jeff Clement, Executive Director, CDMO Business Development North America, PCI Pharma Services said, “Currently, the greatest factor driving parenteral manufacturing is COVID-19. When the pandemic first caused shutdowns in March 2020, large CDMOs employed emergency products, such as vaccines, to address growing needs. Because of this, many pharmaceutical companies struggled to find production space and had to expand their outsourcing network, which reduced the overall global capacity for life-saving treatments. Small and mid-size CDMOs began taking on projects larger CDMOs previously handled, forcing the smaller organizations to implement new procedures and add new equipment. These CDMOs successfully emerged as key players in the pandemic pharmaceutical supply chain because they integrated new technology, remained flexible and maintained constant communication with their clients to meet their needs in a dynamic market.”

As global supply chains lag, the importance of relationships rivals manufacturing capabilities. Dave Powell, VP of Business Development,  Grand River Aseptic Manufacturing (GRAM), said, “The COVID-19 hangover continues, driving supply constraints for consumables, commodities, and fill-finish capacity. Lead time for materials far exceed the lead time for tech transfer and production time, catching pharma and biopharma off guard when planning clinical trial supply. Investments in fill-finish capacity, due to highlighted constraints during COVID-19, will eventually lead to greater options for pharma and biopharma companies. This will also lead to greater competition among CDMOs.”

Avoiding delays in the current manufacturing environment is key. According to Powell, CDMOs are making major investments in filling capacity and flexible technology that serves a range of products and varying batch sizes. “For example, GRAM invested in the Bausch+Ströbel VarioSys flexible filling line with SKAN isolator, which is a modular system that allows for product adaptability and scale-up without sacrificing quality,” said Powell. He also noted that reducing dependance on single use technologies can help avoid future constraints. Importantly, Powell emphasized that relationships are the backbone of this industry and CDMOs are dedicated to building closer relationships with commodity and consumable vendors to ensure future supply and priority.

Prior to COVID many industries adopted just in time (JIT) manufacturing, a production model in which products are created to meet demand, not in surplus or in advance of need. As such, JIT is a form of inventory management that requires working closely with suppliers so that raw materials arrive as production is scheduled to begin, but no sooner. The goal is to have the minimum amount of inventory on hand to meet demand. Throughout the COVID pandemic this model exacerbated supply chain challenges.

Mike Babics of Alcami, said, “There has been a multi-year global shortage of common components, filters, and raw materials, often leading to a delay of 30-50 weeks. This has been particularly impactful in the CMO industry as many CMOs were utilizing JIT inventory management so their client’s components would arrive when production was planned to begin. Their goal of having the minimum amount of inventory, due to the high cost of maintaining that supply, has unfortunately meant that many CMOs have been unable to meet their clients’ fill-finish needs. Alcami and other leading CMOs responsible for supplying large numbers of key commercial injectables, fortunately, maintain more extensive inventory stocks than many smaller CMOs.” Additionally, Alcami invested more than $15 million in the most commonly used components to ensure available inventory options for clients looking to initiate new fill finish projects.

CDMOs Respond
For CDMOs, staying abreast of industry trends is central to supporting the industry’s drug development and commercialization needs. Many CDMOs are investing in parenteral capabilities via acquisitions, expansion of services, and capacities.

Recro’s CEO, David Enloe, said, “As a CDMO with an emphasis on the small molecule market, it is essential that Recro stay on top of key industry trends in order to be best positioned to support customers with their drug development and commercialization efforts. With the overall percentage of injectable drugs in the development pipeline increasing from 53% to 58% from 2018 to 2020, Recro made the strategic decision to prioritize expansion into this market segment. This continued industry-wide growth necessitated the capabilities to offer formulation and filling into vials, both in liquid and lyophilized form, for its current and future clients.”

As a result of the rapidly growing parenteral manufacturing sector, Recro is working aggressively to expand its service capabilities. These strategic efforts include the company’s recent acquisition of Irisys, a West Coast based CDMO that had recently made investments in injectables and lyophilization equipment.

A key milestone for Recro emerging from this acquisition is the planned upcoming launch of its new fill/finish and lyophilization capabilities. With construction and equipment installation for this service expansion completed at the company’s San Diego facility, final validation and commissioning activities are underway. The company expects that its new automated fill/finish line to be operational early in the second quarter, followed by the launch of its lyophilization technology later in the quarter. Enloe noted that Recro already secured agreements for customer projects involving these new capabilities, highlighting the market demand that originally drove its decision to expand into this area.

Another key industry trend driving Recro’s move into parenteral manufacturing, according to Enloe, involves the growing agnosticism towards dosage form in drug development. “Drug developers are becoming less and less beholden to specific delivery forms for their pipelines, shifting their emphasis instead to specific disease categories. This reality puts increased expectation on CDMOs to support multiple types of manufacturing,” said Enloe. Based on this evolving landscape, Recro believes the ability to support fill and finish projects allows Recro to be able to develop prototypes for molecules of interest in each of tablet, capsule and liquid format.

Parenteral Investments
Current market opportunities have service providers making significant investments in advanced manufacturing capabilities. In January 2021, Thermo Fisher Scientific announced its viral vector manufacturing services through the acquisition of Henogen S.A., Novasep’s viral vector manufacturing business in Belgium, for $875 million. Also, Fujifilm Corp. invested around $928 million into Fujifilm Diosynth Biotechnologies, a CDMO of biologics and advanced therapies.

For these high-value products, pharma and biopharma companies are increasingly outsourcing manufacturing and packaging of their biologics. For example, in December 2021, Prestige Biopharma partnered with Dr. Reddy Laboratories for the supply and commercialization of Prestige Biopharma’s proposed “Trastuzumab” biosimilar in selected Latin American and Southeast Asian countries. Additionally, GreenLight Biosciences, a biotechnology company making ribonucleic acid (RNA) products, and Samsung Biologics, a global CDMO, entered a partnership agreement in which Samsung Biologics will manufacture GreenLight’s messenger RNA COVID-19 vaccine candidate at commercial scale. The partnership aims to accelerate the production of GreenLight’s COVID-19 vaccine candidate for Phase III trials and, subject to regulatory approval, commercial sales. The collaboration with Samsung leverages GreenLight’s existing manufacturing process with technology transfer to Samsung.

John Rim, CEO of Samsung Biologics said, “This collaboration demonstrates a major milestone for Samsung Biologics as we will commence our expanded capabilities and operations to provide one-stop end-to-end messenger RNA production from drug substance to aseptic fill finish to commercial release, all from a single site.” Samsung Biologics has been proactive in accommodating client needs in the biopharma CDMO landscape, including plans to add messenger RNA vaccine drug substance manufacturing capability to the current facility in Songdo, which will be ready for cGMP operations within the earlier part of this year.

Modernization
Some key advances and modernization of facilities and innovative approaches and processes for parenteral development and manufacturing are helping to address current and anticipated future needs. Jeff Clement of PCI Pharma Services, said “With the ongoing global capacity shortage, PCI is continuing to build on its current capabilities to assist existing and new clients in drug development and manufacturing.” For example, PCI added an additional large-scale lyophilizer to our Madison, WI location and is expanding its presence in New England with a supplementary high-throughput commercial facility in Bedford, NH. PCI also recently added a state-of-the-art robotic technology to two sites, San Diego and Melbourne, that can produce prefilled syringes and vials in a sterile environment, reducing room for human error.

Additionally, Alcami’s newest parenteral manufacturing facility in RTP North Carolina is a testament to the entire industry’s transformation, according to Mike Babics of Alcami. “Quality by Design (QbD) should not apply only to the manufacturing process but should begin with the initial facility design and run through the final product release. Our most recent fill-finish facility was built using the underlying principles of QbD to optimize the design and construction and ensure that it would meet its intended purpose as a parenteral filling facility.” Babics noted this encompassed dozens of key factors, including but not limited to the physical layout, utilities, air handling, and material flow, and many more items before the installation of new isolator technology utilizing single-use-systems, with flexible volume filling offering minimal line loss. “This approach is at the core of Alcami’s investment in our new site offering four filling lines for liquid and lyophilized products,” said Babics.

“All told, a bright future is well within reach for the global biopharma industry. Reaching that future, however, will take keen foresight, smart strategy, and expert support – as well as dedicated partners who can deliver those crucial resources,” said Carsten Press of Vetter Pharma. “In the coming years, look for biopharma companies to discover those partners across the entire value chain. We see service providers playing an increasingly vital role in not only helping their customers pursue the path to success, but in finding and shaping that path as well.” 

1. Parenteral Drugs Market Forecast, Trend Analysis & Competition Tracking – Global Market Insights 2019 to 2029. https://www.factmr.com/report/3189/parenteral-drug-market
2. Fill Finish Manufacturing Market Forecast to 2027. https://www.theinsightpartners.com/reports/fill-finish-manufacturing-market
3. Pharmaceutical Fill and Finish Outsourcing Market Forecast to 2028. https://www.theinsightpartners.com/reports/pharmaceutical-fill-and-finish-outsourcing-market
4. Evaluate Pharma World Preview 2021 Outlook to 2026. https://info.evaluate.com/rs/607-YGS-364/images/WorldPreviewReport_Final_2021.pdf
5. IQVIA Report Global Use of Medicine 2020 and Outlook 2025. https://www.iqvia.com/insights/the-iqvia-institute/reports/global-medicine-spending-and-usage-trends-outlook-to-2025