AUTOINJECTOR TECHNOLOGY - De-risking Biosimilar Development With a Clinically Validated & Commercially Proven Disposable Autoinjector

INTRODUCTION

As biosimilar development continues to accelerate with nearly $112 billion in biologic medicines set to lose exclusivity in the global market by 2025, the market is becoming increasingly competitive, putting first-to-market biopharmaceutical companies at a key advantage.¹ With current timelines for biosimilar devel­opment and review from health authorities estimated to be nearly 7 years at a cost of between $100 and $300 million to develop, delays during combination product development and regulatory approvals can impact launch timelines and potential market pen­etration.^2,3 A fundamental area in which biopharmaceutical com­panies can de-risk the launch process is by choosing a suitable autoinjector technology and partner.

Anticipating and retiring inherent risks in biosimilar devel­opment is one of the most essential tasks to be undertaken by companies seeking coveted first-mover status. And yet, the de­velopment and commercialization of biologic combination prod­ucts to treat chronic conditions entails highly complex and challenging processes. Stringent performance requirements, to­gether with increasing regulatory demands and intense competi­tion, contribute to the complexity. Certain factors will be essential in establishing and maintaining an early lead. These include eval­uation and selection of suitable combination product technology, and the selection of a combination product development partner with proven commercial solutions, complementary capabilities, and the expertise to positively address those complexities. A so­lution and partner that can help biopharmaceutical companies manage costs will be essential to achieve commercial success in a market that will only become more competitive. For many bio­pharmaceutical customers, BD and the BD Physioject™ Dispos­able Autoinjector have offered the appropriate combination of technology, documentation, and resources required for timely success.⁴

FACTORING IN A RAPID LAUNCH

What factors are evaluated to ensure a fast biosimilar launch? Various internal market research studies undertaken by BD suggest the chosen autoinjector should be a commercially available device that works in conjunction with a commercially available prefillable syringe.^5,6 To limit the possibility of bottle­necks during assembly and production, the device should incor­porate a simple design, which aims to limit the steps required for assembly to help streamline the production process. Ensuring that development support is available from the device partner is key. This should include assembly guidance documents as well as compliant documentation for regulatory approval. The ability of the device partner to provide fast access to small quantities of product during the development phase will also help support time to market. The device partner should be able to provide flexible support, including services such as combination product testing, and medical affairs and regulatory support, as required. Additional factors can include providing prod­uct customization options and the ability to meet the customers’ cost requirements.

BD PHYSIOJECT™ DISPOSABLE AUTOINJECTOR: ITS MILESTONES CAN STREAMLINE YOUR PATH TO MARKET

With an established track record of delivering medications for more than 10 years, the BD Physioject Disposable Autoinjector has attained some significant milestones. To date, more than 118 million BD Physioject Disposable Autoinjectors have been sold.⁷ What’s more, when inte­grated with the BD Hypak™ Glass Prefill­able Syringe for Biotech, the BD Physioject Disposable Autoinjector has proven to be a dependable system, with greater than 99.999% reliability linked to system inte­gration.⁸ Today, millions of patients and more than 15 pharmaceutical companies benefit from the robust design and manu­facturing quality of the BD Physioject Dis­posable Autoinjector for more than 10 chronic therapeutic indications.

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INTEGRATION: ONE-STOP ACCOUNTABILITY FOR PERFORMANCE OF THE TOTAL DELIVERY SYSTEM

A well-integrated system can help mit­igate system performance risks early in the combination product development process. The BD approach to integration is behind the success of the BD Physioject Disposable Autoinjector system.* BD en­sures components work together, helping avoid integration issues between the drug, the primary container, and the secondary solution, which can delay launch times significantly. The BD approach to integration focuses on ensuring every system component, including the barrel, stopper, needle, needle shield, primary container, and secondary delivery system, is compatible and functions cohesively. This strategy helps to develop a robust delivery system that per­forms as designed and meets regulatory requirements for safety, effectiveness, func­tionality, performance, and usability. The hardiness of this approach has proven it­self over the course of 118 million autoinjectors sold for chronic applications. The BD approach to integration also means that you will have a single partner that can deliver all components of a drug delivery system, along with system-level documen­tation and supporting data which, in turn, create a more readily adoptable format for the critical step of combination product regulatory approval.

HUMAN FACTORS STUDIES & RECOGNIZED EASE OF USE

Biosimilars intended for self-injection must demonstrate high levels of patient safety and ease of use while working within the competitive and price pressures specific to the biosimilars market. In its more than 100 years of developing med­ical technologies to address healthcare challenges, BD has established a patient-centric culture reflected throughout its product design approach. BD conducts human factors engineering testing on its most advanced products across a range of representative users to confirm the inte­grated devices are safe for use as a sys­tem. While biopharmaceutical companies will conduct their own human factors test­ing with the actual formulation and in­tended patient population, by leveraging human factors studies in the iterative de­sign of the BD Physioject Disposable Autoinjector, BD provides assurance in the usability of the combined components and reduces the risk of unforeseen issues.

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To inform and validate the design of the BD Physioject Disposable Autoinjector, BD conducted nine human factors studies, including seven formative and two sum­mative studies,^^ involving more than 600 individuals.^9-11 In these studies, BD exam­ined all aspects of performance, safety, efficiency patient acceptance, and ease of use, including pain perception compared with the use of stand-alone prefilled sy­ringes.^9‡ This work generated essential in­sights regarding the overall user-product interface and demonstrated patients’ pos­itive response and acceptability of both the product design and the user experience.

This emphasis on human factors led to a patient-centric design and the incor­poration of a robust integrated passive sharps injury protection feature. In human factors and clinical studies with over 1,300 simulated injections, the needle covering system integrated in the BD Physioject Dis­posable Autoinjector automatically de­ployed and locked in 100% of cases. ^{9,10^∞} The BD Physioject Disposable Autoinjector also incorporates a patient-centric design that allows the patient to control the start of the injection once the autoinjector is placed on the skin and the cap is re­moved. In a human factors study, 90.8% of patients with rheumatoid arthritis found that the force required to press the button was acceptable and 81.5% of patients found that the three-step injection process with the BD Physioject Disposable Autoin­jector was simple.^{10 §¶}

Specific design features include:

• Demonstrated patient usability and ease of use, especially in patients with limited dexterity eg, patients with rheumatoid arthritis^10,12
• A 360° view of the drug and injection process, allowing 100% drug visibility
• A simple, one-touch injection button for activation¹⁰
• A hidden needle before and during in­jection, which aims to help reduce nee­dle-stick anxiety^13-15
• A protected needle before and after in­jection, which aims to help limit the risk of needle stick injury^13-15
• A cap designed to prevent re-capping once the device has been opened¹³
• Two subassembly components, which aim to limit the steps required for assembly¹³

The patient-centric design of the BD Physioject Disposable Autoinjector was recognized in 2015 with the Ease of Use Award from the Arthritis Foundation.¹⁶

DOCUMENTATION

BD Physioject Disposable Autoinjector comes with full, supportive data packages of system performance to help de-risk de­velopment and support time to market. Documentation and support provided with the BD Physioject Disposable Autoinjector include:

• Customer product specifications
• Customer drawings
• BD Design Verification Summary Report and test methods
• ISO10993 compliance statement
• Materials of concern and safety infor­mation
• Intended use and residual risk analysis statements
• Final assembly recommendations
• BD Physioject Disposable Autoinjector validated direction for use (DFU)^#
• Human Factors Engineering summary report
• List of machine manufacturers for final assembly
• Letter or Authorization (LOA) for Master Files and technical dossier
• ISO-11608 compliance quality state­ment

FAST ACCESS TO SAMPLES

BD provides fast access to samples for clinical use through the BD PartnerPath™ Program to ensure flexibility in supply and support time to market. The BD Partner­Path Program is for anyone with a drug in development requiring access to low quantities of product quickly. For this rea­son, BD can ensure availability for a mul­titude of products including primary con­tainers, plunger stoppers, plastics compo­nents, and secondary devices, within 12 weeks.

THE BD PREFILLABLE SYRINGE – AT THE HEART OF DE-RISKED SYSTEM INTEGRATION

Since 2014 more than 3.9 billion BD Glass Prefillable Syringes have been sold to support the delivery of injectable biotech drugs.¹⁷ BD Physioject Disposable Autoinjectors are fully integrated with the BD Hypak™ for Biotech Glass Prefillable Syringe and fully compatible with the BD Neopak™ Glass Prefillable Syringe.

The BD Hypak™ for Biotech Glass Prefillable Syringe is a fully integrated Pre­fillable Syringe and key component in the more than 10-year success and track record for reliability of the BD Physioject Disposable Autoinjector. The BD Hypak for Biotech Glass Prefillable Syringe is a com­mercially proven, sterile, clean and ready-to-fill (BD SCF™) syringe barrel container featuring key compatibility factors for biotech drug delivery. It offers limited reject rates on customer process through fewer visual/cosmetic defects, and improved drug compatibility through specified low tungsten residue levels.^18-19† Its controlled Length Under Flange and gliding specifi­cations are the foundation of its compati­bility with the BD Physioject Disposable Autoinjector.¹⁹

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The BD Neopak™ Glass Prefillable Syringe platform has been developed leveraging the expertise and experience BD has acquired during its more than 30 years of collaboration with the biopharma­ceutical industry.²⁰ The BD Neopak Glass Prefillable Syringe platform is designed to address key needs of biotech manufactur­ers such as drug and autoinjector compat­ibly.^21,23 Fully compatible with the BD Physioject Disposable Autoinjector, the BD Neopak 1 mlL Glass Prefillable Syringe features increased resistance to breakage, specified low and ultra-low tungsten resid­ual levels, and reduced silicone quantity aiming to support reliable perform­ance.^22,23††

SERVICES TAILORED TO SUPPORT YOUR COMBINATION PRODUCT DEVELOPMENT JOURNEY

To every partnership, BD offers a range of end-to-end services based on ex­perience in designing and integrating components into systems and extensive collaboration with drug developers and biosimilar manufacturers. These services are designed to help biopharmaceutical partners choose the correct components and systems for their applications, to as­sess and offer solutions to any potential challenges or sensitivities, and to help pro­duce the necessary data packages needed to demonstrate the safety and perform­ance of the integrated combination prod­uct.

These services include the following:

• Analytical and bioanalytical chemistry capabilities
• Formulation services
• Functional and performance testing
• Clinical/human factors consultancy
• Combination product documentation support and testing
• Process consultancy
• Regulatory support

Combination product support occurs throughout the development process, from matching the right set of components with the formulation in Phases 1 and 2, to validation testing of the system in Phases 2 and 3. BD offers this breadth of capabili­ties in combination with the entire system of components to enable customers to an­ticipate and resolve challenges before they become issues from a system performance perspective.

SUMMARY

Depth of in-market experience with primary containers and secondary solu­tions, confirmed rigor in product develop­ment processes informed by more than 30 years of expertise in injection science and translational research, and an extensive global manufacturing network, are advan­tages BD can offer as a partner. BD lever­ages these assets to develop innovative solutions that provide peace of mind for customers and contribute to patient well-being, and de-risked combination product development and commercialization. For these reasons, the BD Physioject Dispos­able Autoinjector has been chosen by bio­pharmaceutical customers developing new biologics or biosimilars in 1mL applica­tions.

*When integrated with BD Hypak™ for Biotech Glass Prefillable Syringe
†As compared to BD Hypak Prefillables Glass Syringes
††As compared to BD Hypak™ for Biotech Glass Prefillable Syringe
**A number of services can be provided at an additional cost
‡In a clinical study with 40 healthy volun­teers, at the end of the last session, sub­jects were told they will have an unscheduled additional injection. The re­sults showed that all 40 subjects (100%) preferred the BD Physioject™ Disposable Autoinjector for that injection (which was not done, the question was solely for infor­mational purposes).
^In a human factors study with 65 pa­tients with rheumatoid arthritis, 100% (n=390/390 injections) of passive sharp injury prevention feature activation was recorded.
∞ In a clinical study with 40 healthy volun­teers, the passive sharp injury prevention feature activation was recorded 100% (n=480/480 injections) of the time.
* In a human factors study with 65 pa­tients with rheumatoid arthritis, after 6 sim­ulated injections, n=59/65 (90.8%) of patients with rheumatoid arthritis gave a score ≥6 on a 0-10 Likert scale for accept­ance of further self-injections with BD Physioject™ Disposable Autoinjector.
¶ In a human factors study with 65 patients with rheumatoid arthritis, after 6 simulated injections, the mean acceptance for the 3-step injection process (perceived required force to press the button, force to maintain the device on skin and perceived visibility of the move of the stopper during the in­jection) was 81.5% where patients with rheumatoid arthritis gave a score ≥6 on a 0-10 Likert scale.
# Directions for Use (DFU) are provided to support development of the instructions for use (IFU)
^^Between 2005 and 2010, BD con­ducted 7 formative and 2 summative stud­ies, involving over 600 individuals.

REFERENCES

1. IQVIA Institute – Spotlight on Biosimilars, June 2021.
2. McKinsey & Company, “An inflection point for biosimilars”, 2020, https://www.mckin­sey.com/industries/life-sciences/our-in­sights/an-inflection-point-for-biosimilars, consulted online January 19, 2022.
3. Bossart, J. (2020), “DEVELOPMENT TIME­LINES – Drug Development Times, What it Takes – Part 2”, Drug Development & De­livery, https://drug-dev.com/development-timelines-drug-development-times-what-it-takes-part-2/.
4. BD Physioject™ Disposable Autoinjector launched with commercialized drugs.
5. BD Sutton’s Creek Qualitative Market Re­search [internal study],Franklin Lakes NJ; Becton, Dickinson and Company; 2021.
6. BD Autoinjector Market Research Prelimi­nary Report, 2022.
7. BD WW Demand Database, 2012-2021.
8. BD Quality System complaint data – Com­plaint extract for reported user complaints related to system integration.
9. Berteau et al. (2010), “Evaluation of per­formance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy vol­unteers.” Patient Preference and Adher­ence, Vol. 4, p. 379-388.
10. Schwarzenbach et al. (2014), “Results of a human factors experiment of the usabil­ity and patient acceptance of a new au­toinjector in patients with rheumatoid arthritis,” Patient Preference and Adher­ence, Vol. 8, p. 199-209.
11. Summary Report – BD Physioject Forma­tive Evaluations (CHFIN 21-31).
12. Physioject™ Human Factors Engineering Report [internal report], Le Pont-de-Claix, France; Becton, Dickinson and company; 2021.
13. Physioject™ design input specification [in­ternal report], Le Pont-de-Claix, France; Becton, Dickinson and company; 2014.
14. Physioject™ design verification report [in­ternal report], Le Pont-de-Claix, France; Becton, Dickinson and company; 2014.
15. Physioject™ external R&D document. BD Physioject™ ISO23908:2011 Assessment of Compliance [external report], Le Pont-de-Claix, France; Becton, Dickinson and company; 2021.
16. Fain W.B, and Mann E., “BD Physioject Disposable Autoinjector Evaluation Report of Consumer Product Accessibility for Users with Arthritis”, Georgia Tech Re­search Institute, Georgia Institute of Tech­nology, April 2015.
17. Internal analysis, BD internal sales (Ven­davo Extract FY14 FY21).
18. Validation Summary Low Tungsten BD Hypak™ for Biotech Prefillable Syringe Barrels [Internal Study], Le Pont-de-Claix, France; Becton, Dickinson and Company; 2012.
19. BD Hypak™ for Biotech customer quality specification, Le Pont-de-Claix, France; Becton, Dickinson, 2017.
20. BD Medical Pharmaceutical Systems, BD Hypak™ Glass Prefillable Syringe since 1975_BD Website.
21. BD Neopak™ 1mlL customer quality specification, Le Pont-de-Claix, France; Becton, Dickinson and Company; 2017.
22. BD Neopak™ 1mlL design input specifi­cation [internal study], Le Pont-de-Claix, France; Becton, Dickinson, 2010.
23. Traction bench test and visual inspection results: BD Neopak™ vs BD Hypak™ for Biotech improved specifications [internal study], Le Pont-de-Claix, France; Becton, Dickinson and Company; 2018.

Victoria Meyer has worked at BD for more than 14 years across several business units in various commercial roles, including sales, sales operations, and regional marketing. She is currently the Senior Global Strategic Marketing Manager responsible for leading 1 mL product platforms across the BD Biologics Portfolio. In this role, she closely partners with Research & Development and other cross functional teams to define, develop, and deliver programs, data sets, and system solutions to pharmaceutical customers to help support combination product development. She earned her MBA from Columbia Business School and her undergraduate degree in Economics from the College of the Holy Cross.