After operating in the parenteral therapeutics space for years, Baxter BioPharma Solutions’ expertise in sterile injectables has only grown—with the potential to expand into biosimilars.

BioPharma Solutions, as the contract manufacturing business unit of Baxter, has the advantage of Baxter’s more than 80 years of parenteral expertise and a manufacturing network of more than 50 facilities across six continents. Founded in 1931, Baxter was the first manufacturer of commercially-prepared intravenous (IV) solutions and has since had a hand in parental delivery systems, sterile contract manufacturing solutions, and various drug categories, such as small molecules, biologics, and vaccines.

“BioPharma Solutions began in 1981, the year Baxter first formed alliances with pharmaceutical companies to package their drugs in IV containers,” said Marie Keeley, Vice President, BioPharma Solutions.

The company’s primary locations are in:

• Bloomington, Indiana
• Halle/Westfalen, Germany
• Round Lake, Illinois

At these facilities, the company specializes in sterile injectable manufacturing solutions, including capabilities in syringes, diluent syringes, lyophilized vials, liquid vials, cartridges, aseptic bags, and cytotoxic manufacturing with expertise in highly-potent, biologic, and cytotoxic compounds with the ability to provide clinical to commercial production.

“As a global CMO, BioPharma Solutions works with a wide variety of clients,” said Keeley. “The company currently provides sterile injectable contract manufacturing services to more than 60 different clients, including a majority of the top 20 pharmaceutical companies. The products that we manufacture for clients are distributed in more than 90 countries.

“We’re constantly innovating in order to provide some of the best services possible to address our clients’ diverse needs and, ultimately, have the most meaningful impact on patients.

“From a regional standpoint, we continue to see strong demand from our U.S.- and European-based biopharmaceutical companies,” said Keeley. “Western-based companies continue to drive the majority of R&D investments but at modest growth rates. In addition, we are also seeing Asian companies’ investments growing at a faster rate.”

 

Markets: Customer Demand

“BioPharma Solutions focuses on sterile injectables,” said Keeley. “This is a fast growing market, fueled by the influx of biologics. In 2015, biologics accounted for six out of the top 10 brands. Many biologics will be losing protection by 2020, making way for biosimilars. We hope to increasingly tap into the biologics/biosimilar space in the coming years.”

In addition, the company’s biopharmaceutical clients have increased the demand for their specialized R&D service offerings. In particular, there is a demand for formulation development, as well as lyophilization development and optimization of lyo cycles for clinical molecules.

“In the last five years, customer demand has increased dramatically for high-value, complex molecules like biologics, immuno-oncology products, and antibody-drug conjugates,” said Keeley. “This increasing complexity requires dedicated facilities with experienced operators and sophisticated equipment, which is very costly to build, driving many companies to turn to outsourcing for this manufacturing.”

Client Interfaces

“At the outset of a project, we aim to get a detailed understanding of the product in question, including its physical properties, API, additional ingredients, process for manufacturing, testing, and packaging requirements,” explained Keeley.

In addition to inquiring whether a project is a technical fit, BioPharma Solutions also asks commercial questions during the initial client interface, such as:

• The product’s regulatory pathway
• Timeline for manufacturing and launch
• A forecast of the product’s first five years in-market

“This information enables us to ascertain whether the project is a good fit technically with our capabilities,” said Keeley, “and if so, establish the project scope.”

Once a service agreement has been signed, the company then provides a dedicated project team for each client. Project managers lead these teams, many of whom are scientists, have technical backgrounds, or are certified project management professionals. The team works with the client to create transparency and alignment to bring their product to market.

CMO Challenges: Parenteral Drugs & Highly-Potent Compounds

“Parenteral therapeutics present a variety of scientific and technical challenges, including reformulation, stability, chemical degradation, compatibility, leachables and extractables, and precipitation,” said Keeley. “And yet, this is the type of challenge that Baxter has taken on since the company’s inception.”

With 80 years of experience in the industry—a track record nearly unparalleled in pharmaceutical manufacturing—the company has years of expertise to draw from.

“As a CMO, we are proud of our expertise in the formulation, production and purification of solutions, and welcome the opportunity to work with partners to overcome these and other challenges to help ensure product quality and ease-of-use,” said Keeley.

Parenteral drugs present other challenges, however, such as those involving biomolecules.

“Issues during scale up of freeze-dry cycles from the laboratory to manufacturing are a common concern,” Keeley explained. “Baxter’s Lyo Center of Excellence addresses these issues with a Quality-by-Design (QbD) approach to lyophilization cycle development. Baxter pioneered this approach, which takes into account equipment capability to result in a ‘safe-zone’ of operation and successful transfers from the Center’s laboratory scale freeze-dryers to the facility’s commercial scale lyophilizers.”

Furthermore, highly-potent compounds, including antibody-drug conjugates, are especially challenging to manufacture because they are toxic substances and therefore require complex handling protocols to maintain integrity of the molecule, enhance product sterility, and ensure safety of line operators.

“To address these challenges, we have built dedicated facilities staffed with experienced operators, sophisticated equipment and systems, and have employed rigorous standard operating procedures, training, and risk assessments,” said Keeley.

“BioPharma Solutions’ facility in Halle, Germany, has multiple manufacturing areas with independent air supply and waste disposal systems, including 100-percent waste collection. In addition, our Halle and Bielefeld facilities are certified by SafeBridge doing both parenteral drug substance synthesis and parenteral drug product manufacturing and testing. The Halle facility’s expanded capacity, flexibility, and innovative processes and technologies allow Baxter to stay at the forefront of providing world-class complex sterile parenteral manufacturing to meet the needs of our pharma clients.”

DSCSA: Looking Ahead

As of November 2017, the Drug Supply Chain Security Act (DSCSA) requires that all products in the U.S. supply chain are serialized, which means that any production lines that manufacture and package a product must be able to apply a 2D matrix to the package and a linear barcode or 2D data matrix to the case.

These regulations, complicated to incorporate on its own, can become even more challenging for companies who operate both inside and outside of the U.S.

“Operating as a manufacturer in a complex, global supply chain can make adhering to these regulations challenging,” said Keeley. “That’s why we have invested significant resources into training and infrastructure to ensure we comply with the first phase of these regulations which require manufacturers to track each lot of product and provide detailed information for each transaction.

“We are incorporating additional technology, such as the use of 2D data matrix barcodes on each unit of product and enhanced IT solutions for security and traceability, to be prepared for the next two phases of this regulation that go into effect in 2017 and 2023, respectively.”

In November of 2023, unit-level traceability will be fully implemented across the U.S. supply chain.

Addressing Drug Shortages

However, just because the drugs are traceable within the U.S. supply chain doesn’t mean the supply chain is without flaws. The FDA sends out regular updates on drugs that are currently in shortage. To address these shortages, many companies, like BioPharma Solutions, are taking proactive measures.

“We serve as a back-up supplier for many of our clients and have been able to help alleviate a number of drug shortages by being able to ramp up production fairly quickly,” said Keeley. “In one situation, our client was stocking out of product because their competitor was temporarily out of the market due to quality challenges in their manufacturing plant and asked us to increase our production in order to help them capture more share. In another situation, one of our clients experienced delays in getting a new internal plant up and running and asked us to increase volumes coming out of the BioPharma Solutions’ plant.”

Baxter BioPharma Solutions, a 2016 FOYA winner for Operational Excellence, was recognized by The International Society for Pharmaceutical Engineering (ISPE) for their exceptional leadership in drug shortage prevention at the 12th Annual ISPE Facility of the Year Awards (FOYA) banquet.

Standing Out as a CMO

“At BioPharma Solutions, we are dedicated to delivering optimum value for our partners by helping them solve challenges, supporting their commercialization objectives, and providing confidence of delivery, service, and integrity—knowing that the work we do for clients is ultimately vital to the patients they serve,” said Keeley.

“We collaborate with our clients in order to enhance our clients’ ability to meet their objectives. By providing robust technical capabilities and know-how as well as premier manufacturing facilities, we allow our clients to focus their attention on delivering optimal research and development with the goal of providing life-saving and life-sustaining drugs to patients.”

With more than 80 years of experience, Baxter BioPharma Solutions continues to make a name for itself as a CMO across the globe.

This article can also be found in the July 2016 issue of Pharmaceutical Processing. 

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