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. Reddy’s.

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Agenda

• Autoinjector v.s. Prefilled Syringe

• Interface from Prefilled Syringe to Autoinjector

• Autoinjector/PFS development

• What’s the next – Large Volume Wearable Injector

• Conclusion

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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

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

• 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.

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

• 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

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

• 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

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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

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Interface from PFS to Autoinjector - Challenges and Solutions (cont’d)

• 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.

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Interface from PFS to Autoinejctor - Challenges and Solutions (cont’d)

• 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

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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

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- 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)

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What’s 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

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What’s the next?

“Large Volume Wearable Injector” (cont’d)

• 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

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Conclusion

• The advantages of Autoinjector over PFS mainly lie on ease and safety of use, more robust functional performance and more options for product customization. These undeniable advantages make Autoinjector market grows fast.

• The interface from PFS to Autoinjector facing the challenges both in device design and manufacturing. Proposed solutions to the challenges are focused on improve compatibility between PFS and Autoinjector such as PFS dimensions, AI component geometry and dimensions, materials, etc.

• As a medical device, development process of Autoinjector is in compliance with FDA design control regulation, 21 CFR820.30. There are 5 development phases from concept through launch. Each phase focuses on different considerations of development.

• As an advanced version of Autoinjector, large volume wearable injector meet the user/market requirements which are unmet by Autoinjector and is expected to have significant market share in near future.

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Thank you!