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Chapter 34: A Case Study of Bridging from a Lyophilizate Formulation to an Autoinjector for Patient Self-Administration

  • Gerard J. BruinEmail author
  • Marie Picci
  • Kennneth Kulmatycki
Chapter
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Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 35)

Abstract

The case study in this chapter describes the development of the anti-IL-17A monoclonal antibody secukinumab from a lyophilizate formulation as used during the main Phase 3 program to a commercial autoinjector, including the associated development challenges for the first indication and development opportunities for nonclinical bridging studies in later indications. Moving from a lyophilizate formulation in vial to a prefilled syringe and autoinjector can be potentially accelerated by leveraging prior experience from an established drug or device constituent part in combination with a new device or drug. Technical development bridging studies, accompanied by a strong analytical comparability program, are the cornerstone of a successful bridging strategy and may include drug-device compatibility, design verification, simulated use human factors studies, and a thorough risk analysis. These studies might pave the road for an efficient and lean clinical program.

Keywords

Prefilled syringe Autoinjector Lyophilizate Secukinumab PK comparability studies Human factor studies Subcutaneous administration 

References

  1. 1.
    Bertau C, Schwarnezenbach F, Donazzolo Y, Latrielle M, Berube J, Abry H, Cotten J, Feger C, Laurent PE. Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers. Patient Prefer Adherence. 2010;4:379–88.CrossRefGoogle Scholar
  2. 2.
    Schiff M, Jaffe J, Freundlich B, Madsen P. New autoinjector technology for the delivery of subcutaneous methotrexate in the treatment of rheumatoid arthritis. Expert Rev Med Devices. 2014;11(5):447–55.CrossRefGoogle Scholar
  3. 3.
    Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Exp Ther. 2008;84(5):548–58.CrossRefGoogle Scholar
  4. 4.
    Bruin G, Loesche C, Nyirady J, Sander O. Population pharmacokinetic modeling of secukinumab in patients with moderate-to-severe psoriasis. J Clin Pharmacol. 2017;57(7):876–85.CrossRefGoogle Scholar
  5. 5.
    Kinnunen HM, Mrsny RJ. Improving the outcomes of biopharmaceutical delivery via the subcutaneous route by understanding the chemical, physical and physiological properties of the subcutaneous injection site. J Control Release. 2014;182:22–32.CrossRefGoogle Scholar
  6. 6.
    Struemper H, Murtaugh T, Gilbert J, Barton ME, Fire J, Gorark J, Fox NL, Roth D, Gordon D. Relative bioavailability of a single dose of belimumab administered subcutaneously by prefilled syringe or autoinjector in healthy subjects. ACCP. 2016;5(3):208–15.Google Scholar
  7. 7.
    Freundlich B, Kivitz A, Jaffe JS. Nearly pain-free self-administration of subcutaneous methotrexate with an autoinjector. J Clin Rheumatol. 2014;20(5):256–60.CrossRefGoogle Scholar
  8. 8.
    Cosentyx package inserts FDA and EMA.Google Scholar
  9. 9.
    Blauvelt A. T-helper 17 cells in psoriatic plaques and additional genetic links between IL-23 and psoriasis. J Invest Dermatol. 2008;128(5):1064–7.CrossRefGoogle Scholar
  10. 10.
    Lynde CW, Poulin Y, Vender R, Bourcier M, Khalil S. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71(1):141–50.CrossRefGoogle Scholar
  11. 11.
    Krueger JG, Fretzin S, Suárez-Fariñas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145–54.CrossRefGoogle Scholar
  12. 12.
    Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38.CrossRefGoogle Scholar
  13. 13.
    Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab administration by pre-filled syringe: efficacy, safety, and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484–93.CrossRefGoogle Scholar
  14. 14.
    Paul C, Lacour JP, Tedremets L, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29(6):1082–90.CrossRefGoogle Scholar
  15. 15.
    Tovey MG, Lallemand C. Immunogenicity and other problems associated with use of biopharmaceuticals. Ther Adv Drug Saf. 2011;2(3):113–28.CrossRefGoogle Scholar
  16. 16.
    Reich K, Blauvelt A, Armstrong A, Langley RG, Fox T, Huang J, Papavassilis C, Liang E, Lloyd P, Bruin G. Secukinumab, a fully human anti–Interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in subjects with moderate to severe plaque psoriasis. Br J Dermatol. 2017;176:752–8.CrossRefGoogle Scholar
  17. 17.
    Novartis internal report.Google Scholar
  18. 18.
    US 21 CFR, Part 4; Current good manufacturing practice requirements for combination products.Google Scholar
  19. 19.
    European Medical Devices Directive - 93/42/EEC with 2007/47/EC.Google Scholar
  20. 20.
    Guidelines on medical devices, MEDDEV2.7/1 revision 4, European Commission.Google Scholar
  21. 21.
    ISO 11040-4: 2007 -Prefilled syringes – Part 4: Glass barrels for injectables.Google Scholar
  22. 22.
    ISO 7864: 1993 -Sterile hypodermic needles for single use.Google Scholar
  23. 23.
    ISO 11608-1: 2012 -Needle-based injection systems for medical use – requirements and test methods, Part 1: needle-based injection systems.Google Scholar
  24. 24.
    EN ISO 10993-1:2009/COR 1:2010 - Biological evaluation of medical devices – Part 1: evaluation and testing within a risk management system.Google Scholar
  25. 25.
    EN ISO 23908:2011 - Sharps injury protection - requirements and test methods - sharps protection features for single-use hypodermic needles, introducers for catheters and needles used for blood sampling.Google Scholar
  26. 26.
    IEC 62366: 2007 Medical devices – application of usability engineering to medical devices.Google Scholar
  27. 27.
    FDA CDRH (2011) Applying human factors and usability engineering to optimize medical device design, draft guidance for Industry and Food and Drug Administration Staff, Issued on 22/06/11.Google Scholar
  28. 28.
    ISO14971: 2007 Medical devices - application of risk management to medical devices.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2020

Authors and Affiliations

  • Gerard J. Bruin
    • 1
    Email author
  • Marie Picci
    • 2
  • Kennneth Kulmatycki
    • 3
  1. 1.Pharmacokinetic Sciences, Novartis Institutes for BioMedical ResearchBaselSwitzerland
  2. 2.Device Development and Commercialization, Technical Research and DevelopmentNovartis PharmaBaselSwitzerland
  3. 3.Pharmacokinetic SciencesNovartis Institutes for Biomedical ResearchCambridgeUSA

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