Gautam Shetty, Ph.D. AAPS 2014 Annual Meeting November 6 2014€¦ · Confidential-Unilife Corporation Ocular Drug Delivery Devices Gautam Shetty, Ph.D. AAPS 2014 Annual Meeting November

Confidential-Unilife Corporation

Ocular Drug Delivery Devices

Gautam Shetty, Ph.D.

AAPS 2014 Annual Meeting

November 6 2014


Disclosure 75

• Ocu-ject®, Depot-jectTM have not been reviewed by FDA

• Unilife is the designer, developer, manufacturer and supplier of

aforementioned device technologies

• Speaker is also one of the inventors of aforementioned device technologies

• Macugen® is registered trademark licensed to Valent Pharmaceuticals

• Ozurdex® is registered trademark of Allergan

• InJentle® is registered trademark of Schott AG


Presentation Overview 75

• Conventional Device-Pharma Relationship

• Overview of Ophthalmic Drugs & Drug Delivery Practice

• Case Study : Macugen Clinical Experience

• Case Study : Ozurdex Clinical Experience

• Case Study : Developing Optimal Device Technologies To Deliver

Ophthalmic Drugs


Fitting Every Problem To Existing (Wrong/Lesser) Solutions 75

From a device perspective, a number of requirements need to be taken

into consideration for a drug-device combination product

These requirements are in the context of

• End User Requirements

• Regulatory Requirements

• Industry Standards

• Drug Commercial Requirements

• Drug Clinical Requirements

• Drug Fill-Finish Requirements

• Drug Compatibility & Stability Requirements

It is not atypical for device supplier to focus on only one or few of the

above list

With commoditization of device components, accent is on fitting

problem to existing solutions rather than uniquely addressing problems

Leads to customization burden on pharma or sub-optimal

solutions


Best Versus First 75

Every drug manufacturer wants their drug or drug-device combination to be

“Best-In-Class”; however, there is hesitation to be “First-In-Class”

Resistance to change from a procurement, regulatory and/or formulation

perspective often further constrains the ability to provide the most optimal

device solution, and in many cases constrains innovation itself

There is consideration for the drug manufacturer to be receptive to the idea of

“First-In-Class”, and secure benefits that go with it

searchpp.com blog.tnsemployeeinsights.com


Ophthalmology Has Been In Focus Recently

Ref: CNN.com


Conditions Treated With Injections Into The Eye 75

Ref: Shetty, G., Busimi, A., PDA Prefilled Syringes Conference, 2014


Case Study : Macugen® Prefilled Syringe 75

Drug Macugen (pegaptanib)

Anti-angiogenic drug indicated for treatment of wet Age-Related Macular

Degeneration

Delivered via intravitreal injection

myvisiontest.com



Drug Macugen (pegaptanib)

Device Traditional 0.5mL Glass Prefillable Syringe

with 27G Staked Needle

Li, L., Container Closure Testing Method Development And Validation Of Prefilled Syringes, Am. Pharm. Review, 2013

+

Traditional prefilled syringes with attached (staked) needle have the Needle

embedded in the Needle Shield; this dulls the needle



Needle dulled by Needle Shield is probably inconsequential in the case of skin

injections

However, in the case of intravitreal injection, the dull needle increases the needle

penetration force through the sclera resulting in unacceptable patient pain



Kozak, I. et al., RETINA, 2006, 26(6), 679

The needle in the prefilled syringe

had penetration force ~4X for same

in case of a standard hypodermic

needle (needle not embedded in

needle shield)


Case Study : Ozurdex® Clinical Experience 75


Drug Dexamethasone

Indicated for treatment of

- Macular edema following branch retinal vein occlusion

- Non-infectious posterior Uveitis

- Diabetic macular edema

Implantation of the drug depot in the vitreous cavity




Drug Dexamethasone

Indicated for treatment of

- Macular edema following branch retinal vein occlusion

- Non-infectious posterior Uveitis

- Diabetic macular edema

Implantation of the drug depot in the vitreous cavity

Device Vehicle for Sustained Release

Applicator with 22G Needle

+



The dexamethasone implant is propelled into the vitreous by the applicator

The muzzle velocity of the implant is approximately 0.8m/s

The system relies on viscous drag in the vitreous cavity; however large variations

are possible

Ref: Meyer, C. H., et al., RETINA, 32, 2133-2140, 2012



Select other published complications include

- Implant impacting the lens

- Breaking of the implant post-injection

- Impacting the retina

- Vitreomacular traction

Ref: Meyer, C. H., et al., RETINA, 32, 2133-2140, 2012

Roy, R., et al., CAN J OPHTHALMOL, 48, e15-16, 2013

Bakri, S., et al., J. Ocular Pharmaco & Ther, 28, 547, 2012

Chalioulias, K., et al., Eye, 1, 2014



Migration of the implant to the anterior chamber post implantation

Stelton CR, Townsend J, Peterson LT, Khurana RN, Yeh S. “Surgical Management of Anterior Chamber Migration

of a Dexamethasone Intravitreal Implant.” (submitted to Ophthalmic Surg Lasers Imaging Retina..)


Developing An Optimal Solution 75

Case Study of Ocu-ject Syringe developed for delivery of microliter doses


Identifying Unmet Needs



Identifying Unmet User Needs



Identifying Unmet Pharma Needs



Identifying Unmet Compliance Needs



Identifying Unmet Compliance Needs



Unilife Ocu-ject Address Several Unmet Needs



User Confidence In Delivering Microliter Doses



Accuracy And Precision In Microliter Delivery



Needle Sharpness


Schott InJentle

prefillable syringe

allows for a sharp

needle in a staked

syringe configuration


User Experience In Microliter Delivery



Developing An Optimal Solution 75

Case Study of Unilife Depot-ject Syringe for Drug Depot Implantation


Comparing Unilife Depot-ject Implantation Approach


Unilife Depot-ject – Illustration Of Use

No/Low Pressure

Chamber

High Pressure

Chamber


Conclusions

Acknowledgements

Novel Delivery System Team at Unilife Corporation

- Broaden Horizons to accept novel devices or novel device

configurations to maximize drug clinical and commercial potential

- In-depth understanding of intended use, risk should drive development

of device development at different phases of combination product

development

Documents

Gautam Shetty, Ph.D. AAPS 2014 Annual Meeting November 6 2014€¦ · Confidential-Unilife Corporation Ocular Drug Delivery Devices Gautam Shetty, Ph.D. AAPS 2014 Annual Meeting November