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

1. 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/.
2. 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/.
3. Lyophilized Injectable Drugs Market Size Global Forecast 2023-2032, Global Market Insights, July 2023, https://www.gminsights.com/industry-analysis/lyophilized-injectable-drugs-market.