As the chosen dosage form for next-generation therapies, parenteral manufacturing has advanced substantially over the last decade. As the Food and Drug Administration (FDA) calls for the serialization of all drug products, ensuring quality in parenterals has become especially important for contract development and manufacturing organizations, with many adding quality-by-design (QbD) into operations. Among other trends in this rising market is the call for sustainability in production and even “green packaging” delivery methods, as well as movement toward flexibility in operations.

Market growth
The rise of drugs that require more complex formulations, such as biologics, has affected the pharmaceutical supply chain in numerous ways. Biologic drugs are overwhelmingly delivered intravenously; this has notably shaped the parenteral market. Parenteral administration is a key area of opportunity, especially as biologics have become mainstream—with no indication of a slowdown. Instead, the global parenteral packaging market is expected to experience significant growth. According to Zion Market Research, this market was valued at $8.69 billion in 2017. By the end of 2024, however, the parental packaging sector is expected to command $18.2 billion with a compound annual growth rate (CAGR) of 11.14%.¹

Meeting the demands of a global population
The drivers for this increase include a spike in the total global geriatric population and an overall rise in the rates of diseases and chronic conditions within the population. This is observed internationally. As developing nations now have increased access to pharmaceuticals and biotechnology, parental treatments will continue to be distributed and administered worldwide.

North America makes up the largest segment of the parenteral market, with Asia expected to grow significantly. According to Zion Market Research, some of the most formidable players in the flexible parenteral product market include RPC Group, Unilife Corporation, Gerresheimer AG, Stevanato Group, Berry Plastics Corporation, Nipro Corporation, MeadWestvaco Corporation, Schott AG, Dickinson and Company, Inc., and West Pharmaceutical Services.¹

Call for sustainability
A noticeable trend in the packaging of parenterals is the use of biodegradable plastics, which is predicted to drive market growth and innovation, as well as expansion. There is a global demand for the use of “green” or sustainable packaging in the pharmaceutical industry, which is indicative of a greater shift.¹

Stemming from this same change in demand, pharma companies are increasingly highlighting their corporate social responsibility (CSR) departments. For instance, Servier has committed to sustainability as part of their CSR positioning. According to Allain de Wilde, corporate social responsibility director, and Loïc Allanos, corporate social responsibility manager for Servier, sustainability does not need to undermine bottom lines. “A formal CSR strategy enables communication of company goals for creating positive social and environmental impacts in collaboration with all internal and external stakeholders—from employees to customers/partners. Our objective is to enable sustainable development,” they said. “To do so, we are taking steps that go beyond legal obligations; it is a business strategy of Servier to be socially responsible as a means for creating value for all stakeholders and growth opportunities for the company.”²

Flexible packaging and development
Parenteral packaging makes up a broad category of a segmented market, comprising an array of packaging options, such as plastic, glass, small and large volume bags, ampoules, vials, prefilled syringes, and cartridges, as well as ready-to-mix systems.¹ As packaging has become more flexible, so has the machinery needed for its production. Flexible machine platforms give industry developers and manufacturers the ability to make more kinds of products. Christian Treitel, director of business development pharma, Bosch Packaging Technology, explained the difference flexibility has made in manufacturing. “A wider variety of packaging styles—ready-to-fill syringes and, recently, vials and cartridges—and flexible machine platforms offer pharmaceutical manufacturers the flexibility for different products and requirements,” he said.³

Hope for an automation solution
Although the FDA has recommended automation in pharmaceutical manufacturing, when it comes to biologics and more advanced products, the technology has yet to be developed. Continuous manufacturing is attractive because it offers both time and cost benefits. Automated production lines are able to run 24/7 while reducing the cost of labor. This would be a tremendous industry benefit and could mean more drug product at reduced costs. Though automation technology is easier to achieve in oral solid dose and small-molecule API production, the quest for continuous solutions in the manufacture of next-generation therapies will continue.

However, challenges to continuous manufacturing persist. For instance, procuring the proper machine may be an unexpected hurdle in production, especially if a manufacturer has a relationship with a single equipment supplier. The materials of the machine must also be compatible with the chemical formulation; for instance, if a machine is stainless steel, it is crucial to avoid acidic compounds for risk of erosion.⁴

Putting single-use tech to use
A single-use strategy is typically employed in parenteral manufacturing and is used for antibodies, proteins, vaccines, cell therapy, and gene therapy. Although this is the current manufacturing solution, a single-use strategy also presents its own unique set of challenges.

Concerns associated with single-use technologies include the compatibility of parts among different suppliers. “Implementing single-use brings with it new challenges that traditional facilities do not face, such as ensuring skids from different vendors have compatible connectors and common spare components such as clamps,” said Steve Miller, global head of next generation system development, life science, upstream and systems business, Field Millipore S.A.S. Process transfer is another challenge, as is scale-down or scale-up, depending on the size of a reactor. If a typical reactor is 50 L and commercial scale is 2000 L, scale-up or scale-down may not be feasible or come with too great a cost.⁵

Implementing Quality-by-Design
One of the most widespread trends in parenteral development has been the focus on quality in manufacturing. Companies are incorporating QbD into their processes in efforts to eliminate contaminants. Particulate contaminants in parenteral drug products have contributed to drug shortages, which is a worst-case outcome that no company wants to risk.

Unfortunately, the intricacies of the development process have led to more opportunities for particulate matter to affect production. This is particularly true for parenteral packaging processes, such as with pre-filled syringes—it is not uncommon for proteins to interact with the components of the packaging systems under certain conditions. Manufacturers are looking to combat this issue by drawing awareness so that it can be prevented and by optimizing all internal quality management systems through audits, visual inspection, and the design of systems for product monitoring that will alert manufacturers to any potential risk of a hazard occurring.

The goal of QbD is to manufacture correctly from the start. Time and cost are the main challenges to ensuring a facility’s QbD. A QbD approach to quality requires increased testing and labor in research and is often the outcome of a strategic partnership with suppliers—though finding the right one can be a hurdle. However, once implemented,  issues will be reduced and there will be a financial benefit over the long term and improved operations overall.

Pushing parenterals globally
As both the market and the demand for parenteral products continue to grow, so will this segment. The next breakthrough will likely be delivered parenterally. As patient populations become more comfortable with self-administration, parenterals will continue to grow internationally. 

References

1. https://globenewswire.com/news-release/2018/09/04/1564617/0/en/Global-Parenteral-Packaging-Market-Will-Reach-USD-18-20-Billion-By-2024-Zion-Market-Research.html
2. https://www.pharmasalmanac.com/articles/corporate-social-responsibility-as-a-driver-for-improved-sustainability
3. https://www.contractpharma.com/issues/2018-04-01/view_features/continuous-vs-batch-production/53332
4. http://www.pharmtech.com/integrating-single-use-systems-pharma-manufacturing
5. http://www.pharmtech.com/parenterals-particulates-and-quality-design