Interface from PFS to Autoinjector - PFS & Injectablespfs- · PDF fileInterface from PFS...

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Transcript of Interface from PFS to Autoinjector - PFS & Injectablespfs- · PDF fileInterface from PFS...

  • Joyce Zhao

    September 27, 2017

    Interface from PFS to Autoinjector

    DISCLAIMER: The views expressed in this presentation are my own and do not represent the opinions of Dr. Reddys.

  • 2

    Agenda

    Autoinjector v.s. Prefilled Syringe

    Interface from Prefilled Syringe to Autoinjector

    Autoinjector/PFS development

    Whats the next Large Volume Wearable Injector

    Conclusion

  • 3

    Autoinjector (AI) v.s. Prefilled Syringe (PFS) - AI has undeniable advantages over PFS

    Autoinjector is more advanced than Prefilled Syringe (PFS) Human Factor

    Functional performance

    Product customization

    Human Factor Usability & Engineering

    Functional Performance Product

    Customization

  • 4

    Autoinjector (AI) v.s. Prefilled Syringe (PFS) - AI has undeniable advantages over PFS (contd)

    Human Factor Usability & Engineering

    Prefilled

    Syringe (PFS) Auto-

    injector (AI) Advantage

    (AI over PFS)

    Administer Method

    Manual injection

    Automatic injection

    - Easier to use - Possible for user with impairment

    in vision and/or dexterity to self-administration injection.

    - Clinic visit may not be required.

    Needle Stick Injury safety

    feature Active step

    Passive feature

    - Significantly reduce needle stick injury.

    Needle hiding No Yes

    - Significantly reduce needle phobia anxiety resulting in preference to AI and adherence to therapy

    Ergonomic design

    Requires good dexterity for

    injection administration

    Minimum requirement for dexterity.

    - Make self-administer injection possible for patients with impairment in dexterity.

  • 5

    Autoinjector (AI) v.s. Prefilled Syringe (PFS) - AI has undeniable advantages over PFS (contd)

    Functional performance

    Prefilled Syringe (PFS) Auto-injector (AI) Advantage (AI over PFS)

    Dose Accuracy

    Rely on filling and user compliance.

    Well controlled by associated mechanism.

    - Ai is more consistent in terms of dose accuracy, resulting in better efficacy.

    Needle depth control

    No Yes - More consistent with injection depth and

    efficacy. - More user compliance.

    Injection time

    No control Normally 2 20 seconds

    - AI provides relatively short injection time which benefits patients with certain disease.

    - Short injection time meet the requirement under emergency conditions.

    Use for emergency

    Yes Yes - Quicker injection can be completed by using

    AI due to the simple activation mechanism, two-step pull-push or three step activation.

    Dose selection

    No Feature is available - AI is flexible in terms of dose selection.

    Picture from Noble

    http://www.gonoble.com/auto-injector-images/

  • 6

    Autoinjector v.s. Prefilled Syringe (PFS) - AI has undeniable advantages over PFS (contd)

    Product Customization

    Internal design customization to meet requirements for specific drug, injection time, injection depth, etc.

    External look and feel customization to differentiate product.

    Product differentiation by external look & feel customization.

    Customization in spring force, needle gauge, needle length to meet the requirements for specific drug viscosity, injection time, delivery volume, etc.

    Picture from ORENCIA BMScustomerconnect.com

    Picture from in-pharmatechnologist.com

    Picture from MPR

    https://www.orencia.bmscustomerconnect.com/how-to-take-orencia/clickject-autoinjectorhttp://www.in-pharmatechnologist.com/Drug-Delivery/Create-painless-devices-for-quicker-regulatory-approval-says-BDhttp://www.in-pharmatechnologist.com/Drug-Delivery/Create-painless-devices-for-quicker-regulatory-approval-says-BDhttp://www.in-pharmatechnologist.com/Drug-Delivery/Create-painless-devices-for-quicker-regulatory-approval-says-BDhttp://www.empr.com/news/rebif-rebidose-approved-for-multiple-sclerosis/article/274637/

  • 7

    Interface from PFS to Autoinjector

    -Challenges and Solutions

    Challenges in device design and manufacturing have significant impact to performance of an Autoinjector.

    Challenges in Manufacturing

    - Fill and Finish process

    - Final assembly of Autoinjector and PFS

    Challenges in Device Design

    - Compatibility between Autoinjector and PFS

    - Material of Autoinejctor components

    - Autoinjector feature design

    Challenges

    Impact Performances

    Solutions

  • 8

    Interface from PFS to Autoinjector - Challenges and Solutions (contd)

    Challenges in device design includes compatibility between AI and PFS, component deformation during shelf life, and AI component geometry design.

    Optimize component geometry and dimension

    More control on fill and finish process

    SOLU

    TION

    S

    PFS flange breakage during activation and injection.

    Optimize interface between AI and PFS Control PFS shoulder geometry during

    formation

    Severe AI component deformation or breakage during shelf life

    Prolonged injection time

    Optimize material of AI component Reduce the interferences between

    components. Reduce spring force

    Needle gauge Increase driving force (spring forces) Reduce frictional force (lubrication,

    interference reduction, etc.)

    CH

    ALL

    ENG

    ES

    Out of spec dose accuracy

    RNS stays on PFS after cap removal Optimize design of the interface

    between Cap and RNS.

  • 9

    Interface from PFS to Autoinejctor - Challenges and Solutions (contd)

    Challenges in manufacturing includes PFS fill and finish process and final assembly of PFS to AI.

    SOLU

    TION

    S

    Stopper placement in the PFS is out of specification.

    Optimize the stoppering process (mechanical v.s. vacuum)

    Adjust AI design to accommodate the necessary tolerance of stopper position and the air bubble from stoppering process.

    Failures in final assembly PFS and/or AI breakage during final

    assembly Compromised container closure

    integrity Finished AI malfunction

    Optimize interface between AI component and PFS.

    Optimize assembly process parameters

    Adjust AI component design

    CH

    ALL

    ENG

    ES

  • 10

    Autoinjector Development - Device Development Phase

    The five stages to develop a combination product device is to comply with

    the design control process for combination product device development

    required by FDA, 21 CFR820.

    Key deliverables of each stage to ensure

    The design meets the design input requirements

    The device meets the user requirements

    The risks/harms of using the device is eliminated, minimized and mitigated, and

    the device is safe and effective to use.

    Concept

    Device selection

    Container closure selection

    Fill finish selection

    Definition

    Design Input Requirement

    TPP

    Risk management

    Human Factor formative study

    Development

    Design Verification

    Risk assessment (dFMEA, pFMEA)

    Design freeze

    Qualification

    Manufacturing process validation

    Design validation (human factor summative study)

    Design transfer

    Risk management

    Launch/NDA/ANDA

    Design history file closure

    NDA or ANDA review and approval

    FDA 21CFR 8320.30

    https://www.fda.gov/downloads/MedicalDevices/.../ucm070642.pdf

  • 11

    - AI compatibility with drug

    - PFS compatibility with drug

    - AI/PFS compatibility

    Quality and Regulatory

    Autoinjector Development - Considerations

    Considerations vary with development phases, each phase focuses on different aspect of device development

    Manufacturing capability

    Definition

    Development

    Qualification

    Launch/NDA/ANDA

    - DV test - Test method

    development and validation

    - Risk analysis

    - Design input requirement

    - Human factor input - Risk analysis

    - PFS compatibility with drug

    - AI compatibility with drug

    - PFS/AI compatibility

    - Device validation - Manufacturing

    validation (IQ, OQ, PQ) - Risk analysis

    Concept

    - Design output - Regulatory

    submission - Design history file

    (DHF)

  • 12

    Whats the next?

    Large Volume Wearable Injector

    Why Large Volume Wearable Injector

    Large Volume Wearable Injector

    Autoinjector

    Automatic injection Assembled with prefilled container Administer by patient or caregiver

    Volume (up to ~2.0mL) Viscosity (up to ~10cP) Injection time (up to ~20s)

    Volume (up to ~20.0mL) Viscosity (up to ~100cP) Infusion time (up to ~5 hrs) Customize infusion rate and injection time

  • 13

    Whats the next?

    Large Volume Wearable Injector (contd)

    Challenges

    Prefilled container closure system Most of the prefilled container/cartridges use for Wearable Injector needs customization to

    compatible with the device.

    Biocompatibility

    Skin sensitivity to adhesive

    Needle stays in body for a longer time

    Manufacturing

    Fill finish customize cartridge

    Final assembly

    In the Future More user centric

    Safe and minimum use error

    More biocompatible

    Wider therapy regime

  • 14

    Conclusion

    The advantages of Autoinjector over PFS mainly lie on ease and safety of