Issue:May 2024
SPECIAL FEATURE - Prefilled Syringes & Parenteral Delivery: Next-Gen Injections Feature Technology & Reconstitution
The 2023 winners of the Parenteral Drug Association (PDA) Drug Delivery Innovation Award is a good indication of the current status of the parenteral and prefilled syringe (PFS) sectors and how innovation is moving it forward. The Innovation Award went to Merck KGaA for the Digital Platform for Enhanced Adherence Tracing. The innovation is a secure and scalable ecosystem helping to monitor real-time data received from autoinjectors. With the market for parenteral combination products evolving over the last couple of decades, connecting devices have become almost critical. Wearable technology has become valuable for managing patient conditions, ensuring compliance, and gathering real-time data. Now, the global connected drug delivery device market is predicted to grow 23.4% and reach $25.6 billion by 2030.1
Another interesting segment of the market to watch is lyophilized injectables. This segment represents a crucial intersection of innovation, patient care, and market dynamics. Surging demand for more stable and longer-lasting formulations and the rising prevalence of chronic diseases necessitates the development of more effective and convenient drug delivery systems, thus driving demand for lyophilized injectables.2 In 2022, the market was valued at around $280 billion; by 2032, analysts expect it to soar to $988 billion.3 Advancements in biotechnology and pharmaceutical manufacturing techniques are enhancing the efficiency and scalability of lyophilization processes, opening new avenues for growth.2
In this area, PDA presented the Partnership Innovation Award to Stevanato Group, Bayer US LLC, and Vetter Pharma-Fertigung for the Diluent PFS for reconstitution and administration of a lyophilized biologic. According to PDA, the goals of this partnership were to solve a potential compatibility issue with the diluent PFS and biologic drug product and reduce the gliding forces of the diluent PFS during drug product reconstitution.
This exclusive, annual Drug Development & Delivery report highlights other innovations from key players in parenteral delivery and prefilled syringes, with focuses on: safety; meeting regulatory requirements; cost; fill/finish; and dosing.
Aenova: Investing in a Comprehensive Fill/Finish Portfolio
Aenova, a leading international CDMO, has a long tradition in sterile manufacturing at its Latina site. Over the past two years, more than $20 million have been invested in Latina to offer customers modern, Annex 1-compliant, aseptic filling technology for sterile dosage forms, especially vials and PFS. This new manufacturing area has already been approved by the Italian authority (AIFA). Aenova is further investing along the entire process of manufacturing infrastructure, analytical capabilities, and cold chain warehouse, offering customers a comprehensive portfolio in the fill/finish area.
“At the Aenova Site Latina, we offer manufacturing services to a global market, with high levels of expertise, for both clinical trials material manufacturing and commercial supply,” says Paolo Abbate, Managing Director at Aenova’s Latina site. “Our new filling line can support batches from 10L to 1,500L in size, working with both disposable and stainless-steel equipment trains. Our line is a RABS line, enabling increased flexibility and easier process customization.”
Technology transfer activities and the PPQ strategy are established in agreement with customers and are fully compliant with cGMP guidelines. Quality control supports in-process control, product release, and stability testing, while also providing a comprehensive service for microbiological and chemical testing.
“Aenova prides itself on its flexibility in finding solutions and has available space for further facility expansion,” says Mr. Abbate.
ApiJect: Helping to Open New Markets & Reduce Costs for Injectables
“The market needs an affordable, environmentally sustainable, and easy-to-use prefilled injector that can expand access to safe injections for all people in all markets,” says Bo Kowalczyk, Chief Commercial Officer at ApiJect. In addition, there is need for a more efficient and environmentally friendly sterile fill/finish process capable of meeting the demand for prefilled injectables in western markets, yet be cost-effective for global health markets, and scalable to meet the need for surge capacity in times of crisis (like another epidemic/pandemic).
“ApiJect is transforming drug delivery by making it possible for more injectables to reach more markets in a cost-efficient prefilled format,” he says.
The ApiJect Prefilled Platform uses a device design and manufacturing process that combines temperature-controlled Blow-Fill-Seal (BFS) aseptic fill/finish with attachable plastic component design. “BFS is an efficient, advanced aseptic process that is highly automated with a compact, simple supply chain, and can scale up to 15 million units per machine per month,” says Mr. Kowalczyk. Additionally, ApiJect devices can be equipped with safety features like needle shields and auto-disable mechanisms, as well as single-dose packaging to enhance convenience.
Patient convenience, ease of use, and safety are key benefits of prefilled formats. The need for self-injection is becoming more of a necessity and is not limited to remote patient monitoring. Healthcare systems are striving to reduce costs, resulting in a shift from hospital to clinics, outpatient services, pharmacies, and at-home self-injections. “This trend requires a user-friendly, simple, and uncomplicated device,” he says. “And, patients prefer a device that is easy to use and has a straightforward disposal process.”
The growing adoption of environmental, social, and governance (ESG) considerations are causing an increased focus on waste management reduction and more eco-friendly materials and technologies. He says: “While eco-friendly adoption is important, companies also need to keep affordability, sustainability, and accessibility in mind when evaluating device compliance. The ApiJect Drug Delivery Platform can both deliver on ESG goals while also meeting the world’s growing need for safe, injectable formats.”
He explains that BFS is eco-friendly due to its reduced material waste, lower energy consumption, reduced carbon footprint, and elimination of terminal sterilization. And when ApiJect converts that BFS container into a prefilled injector, it does so with a manufacturing process that is as price-efficient and scalable as the standard vial-plus-syringe format – with the safety of a prefilled, single-use device, he adds. This technology can allow for a shift from glass vials/PFS to plastic-based prefilled formats, resulting in much less energy for manufacturing, transportation, and incineration.
ApiJect’s first prefilled injector made on the Prefilled ApiJect Platform has not yet received regulatory approval; FDA approval for its first combination product is expected in early 2025. “Today, we are working with several pharma partners to achieve global market acceptance via a scalable, cost-effective, prefilled injection device that, when combined with their drug or vaccine, could increase vaccine uptake and meet the requirements of global health authorities and markets,” says Mr. Kowalczyk. Key stakeholders from multiple global health markets have been actively engaged and support submission when ready.
Aptar Pharma: Helping Pharma Manufacturers Meet New Annex 1 Requirements
In the pharmaceutical sector, ensuring the safety and effectiveness of injectable medications is of utmost importance. Particulate and microbial contaminations are among the main cause for FDA recalls as they can put patients at risk. The increasing quality expectations of the industry are accompanied by a tightening of regulatory requirements, which intensifies the pressure for manufacturers to guarantee the purity and safety of their drugs. Additionally, the growing focus on biologics and biosimilars within research and development is accompanied by a need to minimize development risk. “Choosing the right partners throughout drug development journeys is crucial to accelerate market access and ensure patient safety,” says Estelle Verger, Business Development Senior Manager at Aptar Pharma.
These observations align with the latest update of Annex 1 by the European Medicines Agency’s Good Manufacturing Practices (EMA GMP), which emphasizes the criticality of contamination risk mitigation. This update requires manufacturers of sterile products to implement a comprehensive contamination control strategy, not just within their own operations, but also throughout their upstream supply chain.
Aptar Pharma, a leading manufacturer of primary packaging solutions, offers solutions that can help pharma manufacturers meet new Annex 1 requirements and take their contamination control strategy to the next level, she says. “When working with primary packaging components, microbial and particulate contamination could come from the components themselves, their packaging or be accidentally introduced on the filling line during aseptic transfer,” Ms. Verger says.
To address the first situation, Aptar Pharma developed PremiumFill®, an improved manufacturing process for elastomeric closure components that leverages robotization and clean rooms to reduce the risk of contamination during production. She explains: “This improved process enables improved specifications on key contamination criteria (i.e., fibers, embedded particles, loose particles, biological contamination) as listed in the Annex 1 revision. PremiumFill components use the same rubber formulations and designs as standard products, allowing manufacturers to easily upgrade their operations, without requiring regulatory reapproval.”
As of Annex 1 revision, sterile drug manufacturers must be able to demonstrate and check the sterility of their primary packaging. To answer this need, Aptar Pharma offers Ready-To-Use gamma sterilized vial stoppers and syringe plungers, a validated and market-proven sterilization method offering all the required guarantees and certificates.
“The proprietary process for RTU components demonstrates integrity at the point of use, as required by Annex 1, and avoid the use of Tyvek material, which is a potential source of fiber contamination,” she says.
To further minimize risks of introducing extrinsic contaminants during the transfer of components on aseptic filling lines, Annex 1 highly recommends using isolators or RABS. Aptar Pharma aligned with this recommendation by offering components packaged in a large variety of Rapid Transfer Port bags to connect directly to the manufacturers’ filling lines, therefore, helping to limit the risk of accidental contamination.
Ms. Verger adds: “Though the Annex 1 revision imposes stricter guidelines to manufacturers, solutions are already commercially available on the market to help them implement their contamination control strategies, while improving their operational efficiency.”
Artcraft Health: Onboarding Technology Prevents User Errors
Artcraft Health is a demonstration and training device company serving the injectables market, where there is an ongoing and critical need to ensure successful patient onboarding for new drug delivery systems. To meet this need, Artcraft Health provides training devices and patient onboarding programs for the full spectrum of injectables — from prefilled syringes and autoinjectors to electromechanical on-body devices. “With expertise in patient-centered engineering and educational design, Artcraft Health focuses on errorless device training for the parenteral drug delivery market,” explains Marty Mason, Senior Director of Demonstration and Training Devices, Artcraft Health.
Within this market, a key concern for delivery device development and training is environmental sustainability. As companies aim to reduce their carbon footprint and protect the environment, many are developing methods to either reuse syringes or create eco-friendly disposable syringes. “Reusable prefilled syringes are significantly more expensive than disposable syringes, making cheaper, readily available disposable syringes a strong alternative,” he says. “However, strategies that focus on patient training could help ensure prefilled syringes remain cost-effective and compatible with current sustainability goals.”
For example, Artcraft Health has developed a device-onboarding technology called accuDemo™ for reusable delivery devices such as prefilled syringes. The accuDemo technology is designed to prevent 100% of user errors in every onboarding session, thereby helping to reduce the cost associated with prefilled syringes and increase the likelihood of compliance with therapy. “As the parenteral market shifts toward connected devices and remote patient monitoring, technologies like this could increase the effectiveness of reusable prefilled syringes and help address the ongoing industry challenge of patient adherence,” Mr. Mason says.
The strategic use of technology and training can greatly accelerate the success of parenteral programs. For instance, a pharmaceutical client tasked Artcraft with creating a demonstration device and training program for a cutting-edge on-body injection device that could be programmed to deliver the right dose of medication at a specific time without the need for an in-person visit. Specifically, Artcraft Health had to engineer a demonstration unit that would simulate for patients the full 27-hour drug administration experience in a greatly condensed time frame.
“To achieve this, our team reverse engineered the complex commercial device to create a fully functional, fully reusable demonstration unit that used solid-state electronics instead of liquid to simulate the entire 27-hour drug administration experience in just 3 to 7 minutes,” Mr. Mason explains. “The ability to use technology to ‘collapse time’ and deliver an accurate training experience was critical to the success of this parenteral program.”
Although building a demonstration unit is a critical piece of the puzzle, knowing how to simplify and ensure successful patient use is the key to making it effective. For the parenteral market, this is a principle that Artcraft Health calls “Certainty of Use.”
“Simplifying complex delivery methods and packaging them into easy-to-understand educational tools and technologies guides patients to comply with dosing and administration for injectables,” Mr. Mason says. “Taking a truly holistic approach to demonstration device development and training not only provides the highest quality training but also aids in the launch strategy for commercial teams in the parenteral market.”
BD Medical-Pharmaceutical Systems: Integrating Plunger Stoppers Into Combination Products
BD Medical-Pharmaceutical Systems provides a broad portfolio of parenteral drug delivery systems, including glass and plastic prefillable syringes, safety and shielding systems, and advanced drug delivery systems including pens, autoinjectors, wearable and on-body injectors. The company also offers a range of combination product development testing services.
One of BD’s latest innovations is the expansion of the BD SCF™ PremiumCoat® plunger stoppers to include 1-3mL sizes, in addition to the 1mL format that is already available. “This allows us to strengthen our BD Neopak™ Glass Prefillable syringe product portfolio by offering a differentiated system solution with the prefillable syringe, plus the stopper, which addresses the needs of pharmaceutical and biotech companies for the development of complex biologics in larger dose volumes,” says Benjamin Roussel Senior Marketing Manager, BD Medical-Pharmaceutical Systems.
BD SCF PremiumCoat supports a higher predictable system injection performance due to reduced glide force and glide force variability (by up to 51% and 73% respectively for the 1-3mL). This helps to reduce injection time and reduce injection time variability.
In addition, BD SCF PremiumCoat is designed to enable improved container closure integrity with a three-rib design and BD guarantees that all stopper ribs touch inside of the prefilled syringe barrel.
BD also offers a robust system data package to support the integration of the BD SCF PremiumCoat into combination products, such as with a prefillable syringe with or without an autoinjector or safety device. Mr. Roussel says: “This ensures higher PFS system functionality and to get timely availability of the needed information for design, quality assurance or regulatory purpose across the system. Ultimately, it is a way to secure drug-combination performance and, therefore, to support pharmaceutical and biotech companies to deliver their drugs on time.”
As BD looks toward future innovations, sustainability criteria has become increasingly important. When deciding which initiatives to launch, BD Medical-Pharmaceutical Systems uses a tool producing science-based results and Environmental Footprint (EF) data – the product lifecycle assessment (LCA). The study was subcontracted to ERM4 on BD prefilled syringes systems to identify hotspots throughout the full combination product lifecycle end-to-end (including device manufacturing, filling, usage, and end-of-life, but excluding drug manufacturing). The analysis covers the direct and indirect emissions of BD suppliers, manufacturing plants, and customers, and provides a global overview on where efforts should be made all along the PFS.
“The LCA identified priority areas and what we could do in-house with our suppliers and customers,” he explains. Based on these results, the team developed a road map towards real-world sustainability improvements, such as regionalizing suppliers to limit air freight; replicating manufacturing on a global scale; increasing the use of renewable energy; reducing energy consumption and waste; introducing recycled content; and integrating eco-design into new product development and continuous improvement.
“Sustainability criteria has become instrumental in the portfolio management of the pharmaceutical industry to ensure that new product development and the management of legacy products’ lifecycle are aligned with market needs, thus ensuring long-term commercial success,” Mr. Roussel says.
Credence: Addressing At-Home Administration & Sustainability
Treatment in certain therapeutic areas like chronic illness and diabetes management/weight loss management involves frequent dosing regimen – some of them daily, weekly or monthly. This implies use of multiple injectable devices by a patient repetitively over a short- or long-term basis, depending on the disease state. Therefore, an enormous amount of used plastic needs to be incinerated or moved to landfill, which leads to environmental challenges.
“With the industry trend of injectable delivery moving from formal healthcare settings to administration-at-home and heightened sustainability imperatives, injectable device aspects like simplicity, usability, reusability, reliability, and sustainability are becoming key enabling product differentiators in the crowded device market,” says Laxman Halleppanavar, Head of Portfolio Strategy and Management at Credence.
Credence’s Companion® and Dual Chamber™ Syringe Systems both include proprietary integrated automatic needle retraction technology that provides inherent usability enhancements like end-of-dose and safety cues, reduced RNS removal force, and elimination of premature safety activation “by design.” He says: “These injection systems offer superior environmental footprint via reduced quantity of plastic, the use of high quality environmental-friendly plastics, reduced weight, and reduced footprint. The inherent device design allows for a range of customization possibilities to suit various drug characteristics. This is enabling our pharma partners to open new drug candidates that are difficult to co-formulate, promoting simplified and faster combination product development cycles.”
Observing the trends like administration-at-home and heightened sustainability targets, Credence identified an opportunity to maximize the sustainability advantage of its injection systems by enabling use of its delivery systems with a platform of compatible reusable autoinjectors. Credence is collaborating with various industry players with the goal of providing substantial reduction in Total Cost of Ownership and improvement to sustainability profiles for its customers and across the entire supply chain – all the way to end users, says Mr. Halleppanavar.
Curia: Supporting Clients Through Scale-Up & Manufacturing
Curia provides end-to-end services for developing, scaling, and commercializing parenteral therapeutics and vaccines. Its two clinical manufacturing facilities are outfitted to support formulation, lyophilization, and analytical development needs across both large- and small-molecule modalities, as well as clinical batch manufacturing into vials, prefilled syringes, and cartridges. Curia’s commercial manufacturing sites also offer capabilities and capacity to scale-up and validate commercial manufacturing processes into all three formats utilizing in-process engineering to support clients’ product needs. The sites have supported numerous commercial launches and hold strong regulatory track records.
“As a product progresses through clinical trials, more often than not, drug development companies will focus on manufacture of their product into a vial format given the lower cost,” says Ronald A. Aungst Jr., Vice President, Business Unit Operations, Drug Product at Curia. “These drug products are then administered via sterile disposable syringes to patients, however, in latter stages of clinical trials, many companies will focus on opportunities to move to a prefilled syringe or cartridge (for autoinjectors) as the primary packaging of the drug products due to the ease of use for administration by the end user. This aids in the clinician’s and/or patient’s ability to safely administer therapies/vaccines with little need for manipulation of the product.”
Curia has supported several clinical programs that ultimately have resulted in a PFS format. “However, as one example, due to the highly viscous nature of one of our client’s products, even the early-phase clinical trial materials were manufactured into a PFS out of necessity,” says Mr. Aungst. “The viscosity of this extended-release product made it nearly impossible to extract the material sufficiently into a disposable syringe from a vial for administration in early-phase clinical trials.”
Matthew Codd, Vice President of Sales, Drug Product at Curia, says: “Successfully developing the process for filling the product into a PFS became essential. Curia’s network of facilities across its business platform continue to support the successful commercialization of this very impactful product for our client’s patients.”
Gerresheimer: Customizable RTF Syringes Meet Customers’ Needs
Gerresheimer specializes in manufacturing primary packaging such as prefillable syringes tailored to the injectables/parenteral market. The company offers a diverse range of glass and Cyclic Olefin Polymer (COP) products designed to address specific needs within the healthcare industry. If a particular product is not part of its existing portfolio, customizations and product developments are offered to meet a client’s unique requirements.
One example of Gerresheimer’s product/service benefiting a pharmaceutical client involved the development of a customized ready-to-fill syringe for specific applications. “Additionally, we assisted in refining and optimizing manufacturing processes, enabling the establishment of commercial production across multiple international locations,” says Stefan Verheyden, Global Vice President Sales, Pharma & Biopharma Solutions, Injectables, Gerresheimer. “This comprehensive approach ensured the successful implementation of their prefilled syringe/parenteral program, enhancing both efficiency and market competitiveness.”
Prefilled syringes may be a bit more expensive than vials and disposable syringe solutions, but they offer a range of benefits, such as less overfilling requirements, reduced packaging materials, and minimized risks of handling errors during administration. “This makes prefilled syringes for expensive drugs a more economically reasonable packaging choice,” says Maximilian Vogl, Head of Global Product Management, Syringes, Gerresheimer. “This shift from vial to syringe translates into enhanced efficiency and safety, contributing to overall cost-effectiveness in the long run.”
Lifecore Biomedical: Helping Clients Evolve From Syringe to Autoinjector
To address increased capacity needs, safety requirements, and industry trends, Lifecore Biomedical is working with well-established vendors to leverage modern technologies. Currently, the company is expanding fill/finish capacity with recent investments in two new Groninger filling systems with SKAN isolators.
“With GMP-readiness of one system in the coming months, and installation of the second system thereafter, customers will benefit from the innovative technology for vial, syringe, and cartridge programs,” says Jessica Miller, Director of Business Development for Lifecore.
In addition to safety improvements from isolator containment, these systems have capabilities such as independent fill-head operation, enabling in-process control (IPC) and adjustment of fill volume for each individual unit of product. Plus, the new technology incorporates a variety of mechanisms that enable higher yields, maximizing return on investment of precious, often high-value, APIs.
Beyond fill/finish equipment, Lifecore is responding to industry trends influenced by patients. “Many of the new syringe programs involve an eventual path toward an autoinjector format,” comments Ms. Miller. “Autoinjectors are growing due to increases in chronic diseases and the desire for greater patient convenience, as well as benefits related to drug compliance (i.e., better dosing control). Also, from a payer perspective, self-administration removes costs associated with injection in a healthcare setting.”
To help create awareness of high-quality options for our clients, Lifecore has entered into a non-exclusive co-marketing partnership agreement with SHL Medical. SHL Medical is a leader in the design, development, and manufacture of autoinjectors, pen injectors, and drug delivery devices. Ms. Miller says: “The relationship with SHL gives us direct access to experts who can advise on important considerations when a client wants to move from a vial or syringe to a self-injection system. Bringing in that expertise at the start helps set up the program for success in areas like sourcing and analytical testing, which can differ significantly compared to programs without autoinjectors.”
Mitsubishi Gas Chemical Company: 3-Layer Vial Protects Biologics, Gene/Cell Therapies
Mitsubishi Gas Chemical Company, Inc. provides multilayer plastic vials called OXYCAPT for biologics and gene/cell therapies stored at low or ultralow temperature. OXYCAPT consists of three layers: the drug contact layer; an outer layer made of COP; and an oxygen barrier layer made of a novel polyester.
“OXYCAPT can offer a number of advantageous qualities as a primary drug container, such as excellent oxygen, carbon dioxide and ultraviolet (UV) light barrier, strong water vapor barrier, very low extractables, high pH stability, low protein adsorption and aggregation, high transparency, high break resistance, lightweight, etc.,” says Tomohiro Suzuki, Associate General Manager, New Business Development Department, Mitsubishi Gas Chemical Company, Inc.
He adds that OXYCAPT has excellent CO2 and O2 barrier, which contributes to stabilizing the gene and cell therapies. “These drugs are mainly stored and transported with dry ice emitting CO2 gasses, so a CO2 barrier is necessary to prevent CO2 ingress into the vials,” says Mr. Suzuki. “According to our internal study, CO2 barrier of OXYCAPT is about 20 times better than the COPs. Also, no CO2 permeation was observed at container closure integrity testing at -75℃.”
Nemera: Platforms Enhance Patient Safety
Nemera’s products offer a comprehensive solution for the evolving demands of the injectables market, addressing the critical needs of increasing biologics and biosimilars pipelines, mainly used in the treatment of chronic diseases and the growing trend of home and self-administration of biologics bolus injections.
“Our injectables platform, ranging from Safe’n’Sound®, a safety system device for prefilled syringes, to Symbioze™, our reusable large-volume body injector, are all designed to enhance patient safety and support them along their treatment journey,” says Cécile Gross, Marketing Category Manager – Parenteral, Nemera. “To best meet market and patients’ needs, Nemera offers a range of services from research to define design customization requirements, and human factor study to drug-device assembly.”
Indeed, the increase in remote patient monitoring has positively influenced the demand for self-injection, particularly autoinjectors, in several key ways. She says: “The development of remote monitoring has had a main impact on patients’ quality of life, allowing them to manage their conditions more effectively from the comfort of their homes.”
In turn, this has reduced the burden of disease, particularly in the case of chronic or life-long diseases, while playing a role in reassuring patients when administering medication in the homecare setting. To facilitate remote monitoring, the development of connectivity devices allows close monitoring of patient adherence and compliance for their treatments and to adjust injection devices, offering more tailored and effective treatment to patients.
Ms. Gross says that while it is important to consider the cost difference between prefilled syringes and disposable syringes, noting that the higher cost of a PFS is justified by their different use. “Prefilled syringes can accommodate biologics and complex formulations, particularly in the treatment of chronic or severe diseases as in oncology and immunology therapeutic areas,” she says. “In contrast, disposable syringes may not be suitable for such applications due to their limitations in terms of drug compatibility or interaction that may affect the stability and efficacy of sensitive drugs.”
In addition, she says PFS offer advantages in terms of patient safety, enabling integration into the reusable and safety devices that are specifically and ergonomically designed for self-injection. “As a result, while disposable syringes may be a less expensive alternative, they may not always be the most appropriate or effective option for administering certain medications, particularly those requiring special formulations or safe home administration,” she says.
Noxilizer, Inc.: NO2 Sterilization Offers a Variety of Advantages to Prefilled Syringes
Noxilizer offers nitrogen dioxide (NO2) sterilization to pharmaceutical, biotech, and medical device companies. NO2 is a leading alternative to sterilization methods, like ethylene oxide (EO) and vaporized hydrogen dioxide (VHP). Companies choose NO2 to sterilize their single-use prefilled syringes or delivery systems because of the ultra-low temperature (10°C-30°C) sterilization process that may extend shelf life, low to no ingress maintaining drug integrity, minimal vacuum option to prevent/minimize stopper movement, and simple and safe to bring in house to reduce total manufacturing time, explains Maura O. Kahn, Senior Vice President, Commercial, Noxilizer, Inc. Noxilizer customers have purchased sterilizers and installed them in their own manufacturing facility or installed at their contract manufacturing organization (CMO). There is also contract sterilization available in the US and Europe.
As Noxilizer’s customers consider a variety of prefilled syringe designs, she says there has been continued growth of polymer syringes. As an example, one global biotech company approached Noxilizer to evaluate three different syringe designs (polymer and glass syringe barrels). At the same time, the biotech company was evaluating other sterilization methods with these designs. The company’s first choice was the polymer syringe. Ms. Kahn says this was due to the favorable benefits that the polymer syringe brought to the drug product, patient, manufacturing, etc.
“Noxilizer conducted extensive feasibility testing on the designs, as well as provided the company with advice on backstop design, sterile barrier packaging, and process challenge devices,” she says. “The benefits of NO2 sterilization (specifically the ultra-low temperature sterilization process and maintenance of drug integrity due to low/no residuals) enabled the biotech company to move forward with their first choice, the polymer syringe.”
PCI: Comprehensive Injectable Drug Delivery Solutions
PCI is a leading CDMO, providing integrated end-to-end sterile injectable drug development, manufacturing, device assembly, and advanced packaging solutions to increase product speed to market and opportunities for commercial success. Spanning the cycle from development to commercialization, PCI offer comprehensive injectable drug delivery solutions for large and small molecule life-changing therapies.
“Our integrated sterile drug manufacturing and injectable packaging solutions support biopharma companies in optimizing dosing and providing convenient, easy-to-use patient-centric therapies to patients,” says Justin Schroeder, Vice President, Global Technical Services, PCI. “Our consultative approach and extensive experience provides a flexible and agile solution for our clients.”
With remote patient monitoring through telehealth appointments or digital platforms, healthcare providers can remotely monitor patients’ health conditions and adjust treatment plans as needed, removing the need for frequent patient visits to healthcare facilities. Mr. Schroeder says: “These user-friendly drug-device combination products have revolutionized drug delivery, offering patients greater convenience, accuracy, and control over their treatment regimens. This accessibility contributes to the increased demand for auto-injectors.”
As a device agnostic final assembly and packaging solution provider, PCI works with its clients to guide their choice of packaging utilizing state-of-the-art software to analyze sustainable factors down to individual components. By having a complete view of which specific elements of packaging are contributing most to a package’s carbon footprint, clients can make more informed decisions.
“Sometimes small changes can have a compounding impact,” says Mr. Schroeder. “For example, this software revealed that when changing from a plastic tray to a molded, paper fiber tray, global warming impact is reduced by 50%. Together with our clients, PCI work to develop the most appropriate solution that aligns to their ESG goals and budget.”
With the industry evaluating ways to enable a closed loop system whereby they capture and recover used post-consumer devices, this likely will be a more impactful and a more immediate solution than the industry developing a delivery form made of recyclable materials, which then needs to be separated downstream as medical waste, he says.
“On the other hand, disposable syringes contribute to plastic waste, which has become a significant environmental concern,” he says. “In response, manufacturers are exploring ways to develop disposable syringes using biodegradable or recyclable materials to minimize their environmental footprint. Additionally, efforts are underway to optimize packaging and disposal methods to further reduce environmental impact.”
Prefilled syringes as a standalone configuration provide efficiency, eliminating the waste caused by overfilling vials. The design, components (including stopper), and functionality improve dosing control, thereby reducing drug product waste.
Disposable syringes may be cheaper, he adds, but cost is only one consideration and the flexibility of a prefilled syringe as a delivery format alongside benefits of patient-centricity compared to traditional vial and syringe drug delivery options, are driving significant growth of prefilled syringe usage. A prefilled syringe in an autoinjector provides a patient-centric device that supports a high acceptance of self-administration. While the unit cost may be higher, self-administration eliminates the cost of administration within a clinical setting, and removing the need to go to clinic also helps reduce carbon footprint.
“Providing a balance of accessibility/ self-administration without the cost of an autoinjector, advances in needle safety devices such as needle guarding caps and retractable needle systems also aid in reducing stick injuries to those administering vaccines and other injectable treatments,” says Mr. Schroeder. “Ultimately, safety, ease of use, and a positive patient experience leads to better adherence and better health outcomes, which in the long run leads to a more effective overall healthcare spend.”
SCHOTT Pharma: Providing Products That Meet Myriad Industry Trends
As a drug containment and delivery system provider, SCHOTT Pharma is a one-stop-shop for pharma companies, CDMOs, and start-ups. Its portfolio includes prefillable polymer and glass syringes, cartridges, vials, and ampoules, and functional services.
Tom van Ginneken, Head of Product Management Polymer Solutions at SCHOTT Pharma, explains that the company’s products ensure that medications reach the patient in a safe and timely manner, and thereby address major pharma trends, such as GLP-1, ADCs, mRNA, the shift from hospital to homecare, the shift from intravenous to subcutaneous, as well as the manufacturing transformation of pharma companies making use of ready-to-use products.
“We see a change in drug formulation that results in the route of administration shifting from intravenous to subcutaneous,” he says. “This allows for patients to self-inject medications in the comfort of their home. This trend is driven by pharma companies that are manufacturing medications for chronic and lifestyle diseases and try to make the treatment as comfortable for patients as possible.”
He adds that the drug delivery process needs to be as uncomplicated as possible with very few manual steps to ensure that the drug is administered safely and in the right dosage. This is where prefillable containers, such as syringes, come into play as they are prefilled with the exact drug dosage. SCHOTT Pharma supports several such products on the market today, such as autoinjectors with prefillable glass syringes (for small volumes of 0-3mL), wearable devices equipped with prefillable glass syringes or cartridges (for medium volumes of 3-10mL) or larger homecare infusion pumps combined with prefillable polymer syringes (for large volumes of 10-50mL).
“Prefillable syringes actually offer various advantages over disposable options,” says Mr. van Ginneken. “These include a longer shelf life, safer and easier drug administration, the easier option for high-speed filling of medications, and no need for drug preparation steps, which results in lower risk of dosing errors, contamination or infections. On top of that, the total cost of ownership is lower compared to disposable options, making prefillable syringes a preferred choice to ensure a safe and easy drug administration.”
One such example is the SCHOTT TOPPAC® freeze prefillable polymer syringe, which was designed to meet the growing needs of drugs that are stored and transported at low temperatures. The syringes can withstand extreme temperatures without compromising structural integrity or drug stability.
Selkirk Pharma: New Fill/Finish Facility Has Purpose-Built Design
US-based manufacturing is critical to alleviate growing demands and capacity constraints within the fill/finish industry. Recent acquisitions will likely continue to amplify those constraints until new reliable capacity becomes available. Selkirk Pharma is a new fill/finish facility providing state-of-the-art capacity. Its purpose-built design includes isolator technology, high-yield filling, software controlled unidirectional flow, and investment in Pharma 4.0 (digitization of operations) as critical technologies for best-in-class operations.
“We see investment in Annex 1-compliant technology and systems as a requirement for future production and a focus of pharmaceutical companies,” says Tony Murray, Director, Commercial Operations, Selkirk Pharma. “Implementation of software-controlled systems for unidirectional flow prevents cross-contamination and is critical for Annex 1 compliance within a multi-product manufacturing facility. A comprehensive Pharma 4.0 strategy and computer system assurance approach is essential to ensure data integrity.” Additionally, Selkirk has high-yield vial filling capability available for both clinical trial and commercial biologic products and has invested in two new syringe lines to support growing demand for syringe capacity.
He says the market for prefilled syringes and cartridge drug delivery looks very strong and is expected to grow. Self-administration and ease of use of administration in healthcare settings continue to drive the injectable drug market. Chronic conditions requiring regular administration for health issues including diabetes, heart disease, and cancer are at the forefront of the shift. In addition, simplification of delivery and increased safety moving from a multi-step administration to a one-step delivery, is preferred. “Every indication is that this trend will continue as more biologics are considering the use of prefilled syringe and cartridge platforms,” Mr. Murray says.
Simtra BioPharma: Committed to PFS Capacity
Simtra BioPharma Solutions (Simtra) is an independent CDMO specializing in partnering with leading pharmaceutical and biotech firms on injectable drug products. Simtra offers a wide range of manufacturing options for syringe sizes of 0.5–20mL. Its capabilities include rotary piston and peristaltic pump filling, insertion-rod stoppering, excess time-delay function and aseptic formulation.
“Simtra has experience with many different molecule types, such as expertise helping clients select the right container for their product and manufacture it efficiently to meet the demands of the market,” says Benoite Angeline, Vice President, Head of Marketing at Simtra.
The COVID pandemic has accelerated market demand for self-treatment and remote physician consultations, with many patients now more willing to treat themselves and manage their conditions with fewer face-to-face interactions with healthcare professionals, she says.
“As prefilled syringes are ready to use and no manipulation is needed, they are the favored container system for self-administered drugs – not just for diabetes or weight loss, but also for asthma, migraine, multiple sclerosis, arthritis, osteoporosis, sexual dysfunction, and fertility treatments,” says Ms. Angeline. “It’s a big win for healthcare systems as patients don’t need to go to a clinic or ask the pharmacy to reconstitute the drug. A PFS may be more expensive in terms of pricing, but significant savings can be made through eliminating the cost of healthcare overhead, whether that involves a clinic or a pharmacist, or having a nurse administer the product.”
Simtra is making significant investments in increasing its PFS capacity. For example, the company has added a new high-speed syringe line at its Halle/Westfalen, Germany facility, which will be cGMP-ready in Q1 2025. It also recently announced a $250+ million investment to expand its sterile fill/finish manufacturing site in Bloomington, Indiana. A new, state-of-the-art 150,000-sq. ft. building will be constructed to house two high-speed automated isolator syringe fill lines and a new high-speed isolator vial line equipped with three 30-sq. meter lyophilizers. Each process suite in the new building will be fitted with dedicated formulation/compounding rooms.
Singota Solutions: PFS Are Low-Cost, Dose-Accurate Solutions
Singota Solutions is a US-based CDMO specializing in formulation development and aseptic fill/finish for injectable biotech projects through the development and clinical-stage process. Singota utilizes state-of-the-art robotic aseptic filling technology operating within a completely gloveless work cell, ensuring highly repeatable and precise fills for small-batch manufacturing, ideal for the production of preclinical and clinical injectable products in prefilled syringe, vial, and cartridge formats with minimized line losses, explains Will Powers, Senior Director Business Development, Singota Solutions. The company works with proteins, biosimilars, peptides, oligonucleotides, other biologics, and small molecules, and has extended its support beyond manufacturing, offering stability studies, finishing (labeling and kitting), supply chain (storage and distribution), as well as transportation engineering and testing services.
Singota’s development and manufacturing services have assisted several clients in their product development pipelines. Mr. Powers describes how Singota played a significant role for one of its clients in the development of an injectable peptide drug using a PFS format with indications for hematologic and various blood disorders. “Over a multi-year period, Singota provided formulation and analytical development and stability studies for multiple concentrations, placebo formulation, and engineering and clinical batches for Phases I, II, and III clinical trials for both US and European theaters,” he says. “Singota also conducted process studies for lyophilization parameters. The product is currently in Phase III trials.”
This case study illustrates the growing demand for PFS. There is also increasing demand for patient monitoring. Mr. Powers says self-injectable devices lower the cost of administration (no need for a clinician) and a use of a PFS or similar cartridge can facilitate the reality of an autoinjector. The injector can be fitted with data collection capabilities, and when coupled with WiFi, can be transmitted and then monitored by remote healthcare professionals.
“Technology advancements in parenteral presentations over the years have been driven by the need for improvements in quality, convenience, cost of administration, and data gathering,” he says. “The benefits of using PFS are numerous. In the clinic, this format allows efficient, reliable, convenient methods for administration.”
He adds that PFS eliminates the need to transfer product from a vial to a syringe, which reduces costs (no additional handling and disposal of a second container). “While the prefilled syringes themselves might appear to be a costly material item on their own, they provide a number of downstream cost saving, product quality, safety, efficiency and reliability benefits in providing an important means of administration to improve the lives of patients.”
Finally, PFS reduces chances for dosing errors. Manufacturing of the PFS products ensures a sterile product and uniformity of the dose, and dosing errors are eliminated, he says.
Stevanto Group: Range of Integrated Solutions for Faster Market Entry
The growth of biologics is driving the need for new solutions in terms of primary containers, delivery devices, and technologies to rise to the challenge of critical issues such as protein aggregation, inorganic extractables, underdosing, and delamination. This is why Stevanato Group has developed the Alba® prefilled syringe platform for high-value drugs. According to Enrico Barichello, Product Manager for the Syringe Platform at Stevanto Group, the Alba PFS significantly reduces development time, time to market, and the quality costs associated with any wastage of the drug product. “Alba is a breakthrough solution for silicone challenges, achieving minimized particle release and optimal drug product stability,” he says. “It is designed for sensitive biologics – employing a plasma treatment on a standard silicone coating to create a barrier that ensures exceptional stability and resistance over time.”
Another rapidly growing area in the healthcare industry is GLP-1 drugs, which are transforming the treatment of diabetes and obesity. A reliable container supply, smooth operation, and safe and easy self-administration are crucial for these new drugs, so Stevanato Group has developed the Nexa® high-performance syringe system. Mr. Barichello says: “Nexa syringes are optimized for integration in autoinjectors and give consistent gliding and injection force, with ultra-low tungsten and glue residuals, and enhanced cosmetic quality.”
Additionally, the Aidaptus® autoinjector, a two-step, single-use autoinjector with a versatile design, can accommodate both 1mL and 2.25mL prefilled syringes in the same base device – so injections can be daily, weekly, monthly, or quarterly. “Aidaptus is at the forefront of bringing self-administration therapies into patients’ homes due to its unique user-friendly and versatile features, making it ideal for GLP-1 and biologics,” says Adam Stops, Head of Product Management for Drug Delivery Systems, Stevanato Group.
Innovation in moving therapy from hospital to home care is crucial to address the human and financial burdens of managing chronic conditions. Drug delivery systems play a crucial role by enabling complex therapies to be self-administered in a user-friendly way, in a home environment. “Stevanato Group offers innovative user-friendly devices that help ensure patients receive an accurate dose each and every time with minimal inconvenience,” he says. Moreover, he says all devices are designed to minimize user steps and improve the overall patient experience. Each therapy requires a unique solution, which is why the company offers the Alina® pen injector, the Aidaptus autoinjector, and the Vertiva™ on-body delivery system platform.
“Stevanato Group offers a range of optional integrated solutions, including device customization, drug containment solutions, analytical services, and equipment for final assembly and packaging – offering an unprecedented set of integrated solutions for faster time to market and reduced total cost of ownership,” he says. “Our unique approach as a one-stop-shop provider means it can cover the entire product lifecycle, from concept definition to industrial delivery and final packaging.”
Ypsomed: Developing Next-Generation Pens & Autoinjectors
Ypsomed’s comprehensive pen and autoinjector platform portfolio, including UnoPen and YpsoMate, is positioned to support the burgeoning demand for peptide hormones for treating Type 2 diabetes (T2D) and obesity. Ypsomed is building its global manufacturing footprint in Switzerland, Germany, and China, and manufacturing options in the US are currently being assessed. “Ypsomed has ongoing development projects based on UnoPen and YpsoMate with a range of companies active in the peptide hormone space and is developing next-generation pens and autoinjectors to better serve the needs of T2D and obesity patients,” says Ian Thompson, Vice President, Account & Business Development, Ypsomed Delivery Systems.
Disposable or prefilled pens and autoinjectors are still the devices of choice, ensuring easy-to-use and safe self-injections. He says: “The huge demand for GLP-1 drugs for treating T2D and obesity, which are injected weekly, is increasing demand for both pens and autoinjectors. If the drug can be formulated in a pen containing four doses, the number of devices required per patient annually can be reduced significantly compared to single-use autoinjectors.”
Sanner Group: Finding Solutions Where Others Have Not
Springboard Pro provides device design and development expertise from new requirements to approved products for its parent company, Sanner GmbH, or to a third-party for manufacture. Sanner provides state-of-the-art primary syringe and drug container manufacturing, secondary packaging for autoinjectors, pen injectors, pumps, inhalers, and other devices, incorporating electronics, and offers sterilization concepts and box-built-logistic services. Sanner Group has developed devices from initial brief to manufacture, including projects that have faltered with other companies.
“Customers regularly ask us for help where their drug interacted with the syringe in an unacceptable way,” explains Tom Oakley, Vice President of Design & Development, Springboard Pro Ltd. “For example, when the force required to complete an injection could be too high or too variable, or when the plunger exhibits “stick slip” where the injection is far from constant or stops entirely, or the drug could be damaged by its interaction with the syringe, needle, or plunger. Skilled engineers and scientists have been able to establish the root cause of the issues and work out robust solutions.”
Demand for self-injection is driven by increased patient convenience through at-home administration, improved adherence by missing fewer appointments, reduced healthcare professionals’ time, cost, and not needing facilities. This potentially reduces environmental impact by removing the need for patients to travel.
Additionally, disposing of an autoinjector has significant environmental impact and the options for disassembly and recycling are limited due to contamination. “But, the environmental impact of disposable emergency autoinjectors can be justified by preventing loss of life, and should be offset against the environmental impact of patients travelling to receive injections,” he says. “Nevertheless, reusable autoinjectors have gained renewed interest as a way of minimizing environmental impact, and can incorporate disposable subassemblies containing the syringe and needle, but are largely reusable. They tend to require more user steps and be more expensive than disposables, and have a higher initial environmental impact. A reusable device has more scope for additional features such as electronics and connectivity, although these bring their own environmental burden.”
He adds that modern disposable autoinjectors are easy to use and minimize administration errors. But, there may be some additional costs reflected in regulatory, quality, and development. “Factors such as sterilization, documentation, and high capital manufacturing lines are not discernable in the final product, but prefilled syringes need specific raw materials of extremely high purity, which are relatively expensive, and exquisite quality assurance,” says Mr. Oakley. “A developer may also need to make significant i nvestments to perform necessary leachables and extractables and drug stability testing.”
Novocol Pharma: Supporting Fill/Finish Demand for GLP1-RA Cartridge Injectables
Novocol Pharma is a CDMO specializing in sterile cartridge fill/finish, and supports both clinical phase and commercial customers with turnkey services from product development, tech transfer, fill/finish to final device assembly. In addition, through its Duoject Medical Systems device group, Novocol Pharma offers drug delivery design services and drug delivery solutions including a portfolio of reconstitution, injection, and safety systems.
“Self-administration of injectable drug products via pen injector, autoinjector or prefilled syringe continues to be a growing market trend due to the prevalence of chronic diseases, advancing drug delivery innovations and new product development with the intention of reducing healthcare burden and improving patient convenience,” says Eric Lee, Director, Business Development, Novocol Pharma. “This demand is being propelled by the recent boom in demand for GLP-1 RA weight-loss and diabetes treatments.”
Novocol recently completed the installation of a new high speed aseptic cartridge filling line that is well-suited to produce GLP-1 RA drug products, which are commonly filled aseptically in 3mL glass cartridges and then assembled into a pen injector device. This new installation will provide additional capacity of over 50 million units to Novocol’s existing cartridge manufacturing facility.
In addition, solutions from Duoject align with this growing trend of patient-centric drug delivery and reconstitution systems. The commercially marketed PenPrep EVO device, a cartridge-based reconstitution system, addresses administration challenges (including multiple steps and needlestick injuries) for lyophilized drug products that are typically supplied in a standard glass vial and allows for the patient to self-administer the admixture using commercially available cartridge-based pen injector devices.
“Duoject also supports customers with the design and development of all-in-one reconstitution and drug delivery systems to further simplify the patient user experience,” says Mr. Lee. “These novel technologies use standard commercially available vials and cartridges without relying on specialty components such as dual chamber cartridges and syringes where supply and manufacturing capacity may be constrained.”
References
- Connected drug delivery device development, by Michael Earl, Today’s Medical Developments, Sept. 2023, https://www.todaysmedicaldevelopments.com/article/connected-drug-delivery-device-development-wearable-medical-manufacturing/.
- Lyophilized Injectable Drugs Market: Charting Growth to 2032, by Ojas Panse, Apr. 17, 2024, https://www.linkedin.com/pulse/lyophilized-injectable-drugs-market-charting-growth-2032-ojas-panse-vaxhf/.
- Lyophilized Injectable Drugs Market Size Global Forecast 2023-2032, Global Market Insights, July 2023, https://www.gminsights.com/industry-analysis/lyophilized-injectable-drugs-market.
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