Economic advantage of robotic gloveless pharmaceutical isolators

The pharmaceutical industry is changing. As precision medicines and modern drug modalities are reshaping healthcare, smaller, more agile pharma companies are stepping up with fresh ideas. These shifts have made the field more competitive, prompting industry leaders to ask: "How can we optimize the economics of modern drug development?"

With up to millions of dollars in lost revenue per day of downtime on a therapeutic batch run, manufacturers can't afford inefficiencies. One of the major financial risks comes from contamination due to human intervention, particularly in aseptic filling, where a single event can lead to batch loss, regulatory delays, and substantial financial setbacks. To safeguard both product integrity and profitability, industry leaders are increasingly turning to closed system processing to reduce risk and improve efficiency.

Robotic gloveless isolators are a promising closed system solution that reduces contamination, minimizes waste, and enhances manufacturing flexibility. In this article, we'll explore the benefits of robotic gloveless isolators and ask whether they're the key to making aseptic filling smarter, safer, and more scalable.

Check out our new e-book on aseptic filling

Aseptic filling: small steps carry big risks

Aseptic filling is one of the most delicate stages in pharmaceutical manufacturing. Good manufacturing practices (GMP) are crucial at this stage to help maximize sterility of biologics as they are transferred from bulk manufacturing and purification into vials, syringes, or cartridges. Unlike other drug products, these biologic products often can't undergo terminal sterilization due to their sensitivity to heat, chemical treatments, or membrane filtration, making contamination prevention at the filling stage difficult and critical.

The consequences of failure are severe. In a 2023 global market report on aseptic fill finish operations, authors highlighted that even minor errors during the aseptic filling process could pose a considerable risk to patient health (1). Furthermore, a single contamination event can lead to batch loss, product recalls, or even regulatory shutdowns, resulting in potentially millions of dollars in lost revenue.

The growing complexity of contamination risks

Contamination is an ever-present threat in aseptic filling. A 2024 industry analysis of contamination trends found that microorganisms remain the most common type of contaminants, followed by biopharmaceutical impurities and process-related contaminants (2); also see Figure 1. Of even higher concern, the analysis revealed that cross-contamination between different drug products has risen in shared manufacturing facilities, emphasizing the need for better containment strategies.

Fig 1. Contamination trends in pharmaceutical development based on a 2024 industry analysis.

Although conventional aseptic filling takes place in a carefully controlled environment, each step in the process still carries a risk of contamination. These steps include:

1. Preparing a sterile environment
2. Fluid preparation and system setup
3. Precise filling into containers (e.g., vials, syringes)

Each of these steps requires precise dosing, rigorous environmental monitoring, and constant quality control to avoid waste, batch rejection, and regulatory penalties. For example, the US FDA allows for no more than one contaminated unit per 10 000 (3). If a batch exceeds this threshold, it must be investigated and if contamination is confirmed, manufacturers must halt production and revalidate the entire process.

To meet these high standards, industry leaders are increasingly turning to closed systems such as robotic gloveless isolators (4). Unlike traditional filling lines, which rely on manual interventions that introduce variability and contamination risks, robotic gloveless isolators create a fully enclosed, human-free filling environment. But what makes robotic gloveless isolators the most economical solution? Let's explore how robotic gloveless isolators are boosting efficiency, enabling flexible scaling, and reducing waste to deliver real economic benefits.

How robotic gloveless isolators modernize aseptic filling

Aseptic filling methods have come a long way. In the early days, biosafety cabinets allowed operators to manually fill containers in a controlled environment. However, because these cabinets are open to external air, contamination risks remain high. The introduction of conventional filling lines marked a substantial improvement, as automated systems could fill containers in succession with greater precision. Yet, these lines are still housed in cleanrooms where human intervention is necessary, leaving potential contamination points.

The next leap forward came with restricted access barrier systems (RABS), which enclose the filling environment to a much greater extent. Though RABS reduce contamination risks by requiring personnel to interact through glove ports, they still rely on human input, which introduces variability and operational inefficiencies.

Today, robotic gloveless isolators surpass previous systems by eliminating human intervention. Because of this, they have come to represent one of the highest standards in aseptic filling. Their fully enclosed design removes the risk of operator contamination and error, drastically reducing batch loss and helping manufacturers keep up with tight project timelines. Unlike conventional filling lines that require multiple vendors and custom configurations, robotic gloveless isolators offer a standardized solution that reduces complexity and unexpected costs. Furthermore, electronic batch records streamline compliance and batch release, accelerating cash flow by getting products to the clinic faster. Table 1 compares different aseptic processes (5).

Table 1. Aseptic process comparison

	Risk of trial failure	Product quality consistency	Primary container, format flexibility	Product loss ratio	Batch transit time	Capital expenditures	Batch cost	GMP compliance
Semi-automatic line	Low	Very high	Partial	Significant	Low	Moderate	Fair/high	Good
Manual fill/finish	Very high	Very low	Good	Significant	High	Low	Low	Poor
Robotic workcell	Very low	Very high	Good	Low	Low	Moderate	Fair	Excellent

Speeding time to market

Many industry leaders hesitate to adopt robotic gloveless isolators due to concerns about long timelines to implement them. So why does setup take so long, and how can these barriers be addressed?

The lengthy setup of robotic gloveless isolators comes down to one factor: validation. Once an isolator is installed, it undergoes rigorous testing:

• Installation qualification (IQ): Confirms setup, utilities, and documentation.
• Operational qualification (OQ): Verifies automation, airflow, pressure control, and decontamination cycles.
• Performance qualification (PQ): Assesses production under GMP conditions.

Next, material compatibility testing ensures active pharmaceutical ingredients (APIs), excipients, and cleaning agents, among other materials, interact safely with the system. Robotic calibration fine-tunes dispensing and decontamination operations, followed by media fills and contamination testing. Once data is collected, manufacturers submit standard operating protocols and batch records for GMP validation, often followed by a regulatory audit. Finally, staff training, environmental monitoring, and periodic requalification maximize long-term compliance.

The faster a company reaches GMP, the sooner it can generate revenue from drug production. So, how can manufacturers reach GMP faster, while avoiding disruptions to commercial supply? The key lies in choosing a system that aligns with regulatory requirements, such as Annex 1 of the European Union's GMP guidelines for sterile medicinal products (6). In addition, features like automated decontamination and integrated monitoring not only boost compliance but also simplify operations. Standardized, off-the-shelf documentation and vendor-supported operator training can speed up implementation even more. With these systems in place, manufacturers can streamline compliance, minimize delays, and optimize efficiency, ultimately making it possible to achieve a full return on investment (ROI) in as little as one year.

In summary, while the initial setup and validation of robotic gloveless isolators may require significant time and effort, strategies exist to optimize this process and maximize efficiency. Once deployed, robotic gloveless isolators deliver transformative benefits, including streamlined technology transfer, reduced batch failures, and expedited regulatory approvals. These advantages not only accelerate the path to commercialization but also position facilities for effective scalability and long-term success.

Supporting scalability and flexibility in manufacturing

Aseptic filling is a time-intensive process and one of the most resource-heavy operations in pharmaceutical manufacturing. In many facilities, aseptic filling equipment represents the highest capital investment and longest lead time (7). To mitigate these costs, manufacturers often strive to enhance flexibility by enabling conventional filling lines to accommodate multiple products, formulations, or formats and thereby increase utilization and ROI.

Despite these efforts, fill lines often struggle with low overall equipment efficiency, with turnaround times frequently exceeding 24 h. A large portion of this downtime is spent cleaning reusable critical contact parts, which must be sterilized and reassembled aseptically.

Closed systems, such as robotic gloveless isolators, present three major economic benefits associated with their standardized and relatively simple design. First, they minimize utility and installation costs by circumventing the risks and expenses of designing a filling machine by committee. Second, they address inefficiencies by decontaminating the packaging environment—typically using vapor-phase hydrogen peroxide—and minimizing the need for reusable parts, thereby increasing capacity. Finally, robotic gloveless isolators' isolated operational chambers allow them to function effectively in Grade C cleanrooms, which are less expensive to construct and maintain than higher grade cleanrooms, leading to substantial savings.

Achieving a favorable return on investment hinges on processing sizable volumes that maximize operational efficiency. While concerns remain about potential bottlenecks when handling small batches, modern robotic gloveless isolators effectively address these challenges with a simplified interior design that enables faster decontamination cycles. Also, the widespread use of single-use disposable product-contact materials eliminates the need for extensive cleaning between batches, further speeding up manufacturing. Presterilized, ready-to-use (RTU) components are examples of such materials that support scaling with minimal reconfiguration.

Robotic gloveless isolators empower manufacturers to respond to evolving production demands by offering increased production capacity, faster setup and changeovers with RTU components, and shorter decontamination cycles enabled by simplified designs. These features, combined with improved batch transit times through automation, enable manufacturers to adapt seamlessly to evolving production demands while maintaining efficiency and cost-effectiveness.

Figure 2 illustrates the ease of adding capacity by scaling out.

Fig 2. Robotic gloveless isolators reduce the time and expense needed to add capacity for new products with additional workcells to reach capacity requirements.

Robotic gloveless isolators in action

Much like how automation in the automobile industry improved safety and boosted production speeds, robotic gloveless isolators have effectively reduced exposure to hazardous materials, enhanced the safety of medicinal end products, and can potentially provide wider access to medicines. Singota Solutions, a CDMO located in Bloomington, Indiana, USA that specializes in parenteral, early-phase drug development and aseptic filling projects shared their experience using the SA25 aseptic filling workcell from Cytiva (8).

The SA25 workcell is a standardized gloveless filler with specialized robotic components that fill and close nests of vials, syringes, or cartridges (Fig 3). As early adopters, Singota have seven years of experience with the SA25 workcell and during that time they have successfully managed to reduce their sterility failures to zero. These numbers are even more impressive when you consider that Singota's success as a provider of early parenteral drug development for startups and biotechs rests on their ability to handle limited and expensive APIs, small batches, tight and shifting schedules, evolving formulations and changing presentations.

Reduced downtime means more production time, leading to higher throughput and cost efficiency. The SA25 workcell can change between formats in just
45 min with the ability to fill most nested vial, syringe, or cartridge formats from 0.2 to 50 mL. This versatility reduces the need for additional filling machines, providing great utility for CDMOs and companies with diverse product portfolios. Other Cytiva robotic gloveless isolators expand the range of robotic gloveless isolator capabilities, such as the Microcell™ vial filler which is specifically designed for small batches. The Microcell™ vial filler can fill up to 4 different drug products in an 8 h shift. Single-use consumables and a fast 15 min decontamination cycle further reduce fill and changeover times leading to increased efficiency over conventional isolators or RABS. By adopting a modern process with format flexibility and rapid changeovers, manufacturers can enhance competitiveness, increasing win rates in client bids and gaining confidence that demands will be met.

Fig 3. The SA25 aseptic filling workcell is a standardized robotic gloveless isolator filler with specialized robots that fill and close nests of vials, syringes, or cartridges. Left, fully sealed nested vials and press-fit caps. Right, fully stoppered nested syringes.

Another case study demonstrating the benefits of robotic gloveless isolator flexibility comes from NorthX Biologics of Matfors, Sweden. NorthX sees the Microcell™ vial filler from Cytiva as an essential cornerstone of their ability to bridge the gap between academic research and GMP manufacturing to bring scalable clinical solutions to market. The translation of academic research to clinical-scale production continues to face many barriers. Modern medicines are fragile and often must use processes that are aseptic from pooling through to filling to maintain drug product integrity. Also, efficacy of biotherapeutics at smaller effective concentrations means that wasted residual volumes represent lost therapeutic potential. As such, minimizing loss is critical to therapeutic success.

View infographic to see how NorthX and White Raven achieved Annex 1 GMP certification

Considering the increasing need for small-to-mid-batch production driven by personalized medicines and single-patient batches, adoption of robotic gloveless isolators for small-batch pharmaceutical vial filling makes sense. NorthX Biologics chose the Microcell™ system for its flexibility to fill up to 4 different drug products with an average run time of just 8 h for 1200-unit batches. Single-use consumables and a fast 15 min decontamination cycle further reduce fill and changeover times, making this system a highly useful solution for companies looking to build a solid foundation before expanding to meet demand.

Across the industry, it's easy to find similar case studies highlighting the practical benefits of robotic gloveless isolators. However, the economic impact extends beyond these obvious advantages. For example, robotic gloveless isolators' smaller footprint maximizes the economics per square meter of lab space, allowing labs to handle more projects within the same facility with minimal risk of cross-contamination. Additionally, in an era where drug development often involves tiny volumes of highly expensive APIs, the conservative nature of robotic gloveless isolators is a particularly vital benefit as it leads to less waste and more end-product.

Less waste: more medicine

Any unit volume of wasted medicine potentially represents one person left unprotected against a deadly disease. In facilities handling thousands—or even millions—of vials, syringes, or cartridges, this waste can quickly accumulate. For biopharmaceuticals, where producing just 1 liter of drug substance can cost over $500 000, minimizing waste becomes not only a public health priority but also a financial necessity (9). Reducing dead volume not only prevents unnecessary losses but also enhances operational efficiency, increasing the number of patients that receive the treatments they need.

Aseptic filling processes are especially prone to waste during setup, line clearance, and product changeovers. At this stage, even small losses can have a substantial financial impact. However, innovations like real-time continuous environmental monitoring with biofluorescent particle counters (BFPCs) are positively impacting waste management. By containing contamination at the tray level, BFPCs prevent batch-wide losses, delivering cost savings alongside real environmental benefits. As a result, reports estimate that robotic systems can reduce losses to 50 mL per batch, offering advantages for cost-effectiveness and dose availability (10).

Waste doesn't just cost developers. Patients pay the price for inefficient and wasteful processes by adding to the expense of drug manufacturing and drug delivery. Reducing waste doesn't just save money, it improves the upstream economics of healthcare, potentially making these transformative treatments more accessible to patients and more sustainable for manufacturers.

Read about how BFPCs are gaining momentum

The future of aseptic filling

Pharmaceutical companies and contract research organizations across the industry are increasingly embracing the economic and operational benefits of robotic gloveless isolators. While the sterility benefits are clear, the question remains, do the additional advantages justify the upfront investment and deliver sustained value over the long term?

To answer this pressing question, we must consider the cumulative and long-term economic benefits robotic gloveless isolators offer. First and foremost, they deliver competitive efficiency that drives sustained cost savings. Moreover, their integration with real-time continuous environmental monitoring systems, such as BFPCs, ensures that contamination events are contained at the tray level, safeguarding both product integrity and production timelines while minimizing costly disruptions.

Additionally, robotic gloveless isolators provide the flexibility to handle modern drug modalities in a user-friendly, scalable manner, with a footprint that allows facilities to accommodate more projects simultaneously, boosting operational capacity over time. Adding to their appeal, robotic gloveless isolators operate effectively in lower rated cleanroom environments, thanks to their isolated operational chambers. This feature alone translates to substantial and ongoing cost savings by optimizing space utilization and reducing overhead expenses.

When these benefits are weighed against the initial costs of adoption, installation, and validation, the value of robotic gloveless isolators becomes undeniable. While the initial cost of presterilized containers is higher, the savings from not needing washing, depyrogenation, and additional equipment reduce long-term costs. In fact, when viewed through a long-term lens, the decision to adopt robotic gloveless isolator technology is less a question of if and more a question of when. For pharmaceutical manufacturers looking to future-proof their operations, robotic gloveless isolators represent a compelling and forward-thinking solution that's hard to ignore.

Explore other relevant articles

• Key topics and trends in aseptic filling
• CDMO uses robotic gloveless isolator for advanced therapeutics
• CDMO checklist to choose the right aseptic isolator
• How robotic isolator technology aligns to Annex 1 principles
• Why choose robotic processing for small batch aseptic filling
• Biofluorescent particle counters are gaining momentum

REFERENCES

1. Research and Markets. Aseptic fill finish global market report 2023: demand for pharmaceutical and biopharmaceutical drugs bolsters sector. GlobeNewswire News Room. Published April 11, 2023. https://www.globenewswire.com/news-release/2023/04/11/2644121/28124/en/Aseptic-Fill-Finish-Global-Market-Report-2023-Demand-for-Pharmaceutical-and-Biopharmaceutical-Drugs-Bolsters-Sector.html Accessed March 6, 2025.
2. Contamination Trends & Proposed Solutions | Pharmaceutical engineering. ispe.org. Published April 1, 2024. https://ispe.org/pharmaceutical-engineering/march-april-2023/contamination-trends-proposed-solutions Accessed March 6, 2025.
3. FDA. Guidance for Industry Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice Pharmaceutical CGMPs; 2004. https://www.fda.gov/media/71026/download Accessed March 6, 2025.
4. Markarian J. Closed systems for aseptic fill and finish. PharmTech. 2019;43(5):36-39. https://www.pharmtech.com/view/closed-systems-aseptic-fill-and-finish Accessed March 6, 2025.
5. Fuchs C, Mauri S. Why change is inevitable in aseptic manufacturing?https://fedegari.com/wp-content/uploads/2019/03/Why-change-is-inevitable-in-aseptic-manufacturing.pdf Accessed March 6, 2025.
6. European Commission. The Rules Governing Medicinal Products in the European Union Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use; 2022 https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en Accessed March 6, 2025.
7. Thomas F. Streamlining aseptic processes through automation. PharmTech. 2024;48(6):10-13. https://www.pharmtech.com/view/streamlining-aseptic-processes-through-automation Accessed March 6, 2025.
8. Advancing aseptic filling: evaluating the revolutionary SA25 workcell. Singota Solutions. Published March 27, 2024. https://singota.com/advancing-aseptic-filling-evaluating-the-revolutionary-sa25-workcell/ Accessed March 6, 2025.
9. Ekegren J. Minimizing drug product losses in small volume aseptic filling – Contract Pharma. Contractpharma.com. Published January 29, 2016. https://www.contractpharma.com/exclusives/minimizing-drug-product-losses-in-small-volume-aseptic-filling/ Accessed March 6, 2025.
10. Detreille J and Kim P. Reducing time to first-in-human trials with robotic sterile fill-finish manufacturing services. Pharmasalmanac.com. Published 2024. https://www.pharmasalmanac.com/articles/reducing-time-to-first-in-human-trials-with-robotic-sterile-fill/finish-manufacturing-services Accessed March 6, 2025.