Implantable, Dissolvable, Multifunctional, Drug Delivery Device

BIO MEDS

Final Report

May 5, 2014

CHE 4080

Alissa Aylward

Tess Gerber

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Table of Contents

1. Abstract .......................................................................................................................................................3

2. Scope-of-Work (A)......................................................................................................................................3

2.1 Problem Definition.....................................................................................................................................3

2.2 Constraints..................................................................................................................................................4

2.2.1 FDA Approval.....................................................................................................................................4

2.2.2 Current Patents....................................................................................................................................5

2.2.3 Rejection from body............................................................................................................................5

2.2.4 Drug concentration..............................................................................................................................5

2.2.5 Limited time on market.......................................................................................................................5

3. Introduction (T)............................................................................................................................................5

4. Description of Base Case (A).......................................................................................................................7

4.1 Overall Product Description.......................................................................................................................7

4.2 Mass Transfer...........................................................................................................................................15

4.3 Assumptions.............................................................................................................................................15

4.4 Discussion of Solution..............................................................................................................................15

5. Base Case Manufacturing (A)....................................................................................................................15

5.1 Product Manufacturing Flow Diagram.....................................................................................................15

5.2 Major equipment......................................................................................................................................18

5.3 Utilities requirements...............................................................................................................................18

6. Process Alternates (T)................................................................................................................................18

6.1 Silk MPA..................................................................................................................................................18

6.2 Silk MPA Manufacturing Process............................................................................................................23

6.3 Silk MPA Economics...............................................................................................................................24

7. Permitting and Environmental Concerns (A).............................................................................................26

8. Risk Management, Safety and OSHA Requirements (T)...........................................................................26

9. Project Economics (T)................................................................................................................................26

9.1 Economic Basis........................................................................................................................................27

9.2 Price Summary...................................................................................................................................27

10. Conclusions and Recommendations (T).................................................................................................30

11. Future Work (T).....................................................................................................................................31

12. Acknowledgements (T)..........................................................................................................................31

13. References (T)........................................................................................................................................32

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14. Appendices.............................................................................................................................................38

1. Abstract

Implantable drug delivery systems continue to be incorporated within various therapies ranging

from hormones, opioids, antibiotics to oncology applications. Unfortunately, the systems

currently on the market call for extraction of the device and do not provide essential feedback

about the drug delivery that is occurring. Therefore, an alternative system is proposed that would

be biodegradable, have no need for extraction, and would provide feedback. Two technologies

selected for this device are a poly(lactic-co-glycolic) acid (PLGA) and a Silk microprism array

(MPA). The general cost of this process using either technology is relatively inexpensive. The

net present value for PLGA is $5.6 million, with an IRR of 28% and a payback period of 1.5

years. For the Silk MPA system, the net present value is $161 million; with an IRR of 5342%;

and a payback period of about 1 month. Furthermore, the PLGA device was determined to be

the superior technology based upon availability of information, more reasonable economics, and

less potential environmental concerns. Overall, this product obtains all of the goals as stated

above.

2. Scope-of-Work

2.1 Problem Definition

When a patient is given pills or injections the dosage of drug has highs and lows. This is not

ideal for treatment; the ideal situation is to have a constant linear release. Figure 1 below shows

an example of this. Current implantable drug delivery devices obtain this ideal result but need to

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be extracted and provide no feedback. Therefore, this project is centered on developing a drug

delivery device that will be implantable, dissolvable, and multifunctional.

Figure 1. Drug concentration via various delivery methods.

As you can see from the figure above, oral or injection methods have highs that reach into the

toxic threshold and then dip down low; whereas the right graph shows the linear release in the

therapeutic window. One of our main goals for the device is to have the linear release as shown

in the right graph.

2.2 Constraints

2.2.1 FDA Approval

The FDA approval process will consume most of the time before this device can be officially

sold to patients. This device falls under a Class III device as defined by the FDA. Therefore, the

following timeline applies: First, 1-2 years would be needed to complete design. Then, the

process of and Institutional Review Board (IRB) Approval would need to occur. Next, 0-1 year

of the Investigational Device Exemptions (IDE). Then, 0-2 years for Clinical Studies. Next, 90

days for the Premarket Notification 510k, and finally 1-2 years for the Premarket Approval

(PMA). Then Post-Approval Studies would need to be performed.

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This device would need approved by the FDA as well as the IRB. The 510k is required for a

device that is introduced to the FDA for the first time and is going to be marketed or

commercially distributed, and thus would be needed for this specific device. The PMA needs

studies to evaluate the safety and effectiveness of Class III devices, which are where the clinical

studies come in. All FDA approved devices have post approval studies to assure safety and

effectiveness of the approved device.

2.2.2 Current Patents

Similar devices on the market cause this constraint because this device needs to be ensured not to

infringe on any current patents.

2.2.3 Rejection from body

Another constraint is that the host’s body could reject this device. This is unlikely, but all options

and scenarios must be considered.

2.2.4 Drug concentration

If a drug concentration is too high it can cause damage to tissues and organs. Therefore the rate of release will need to be determined for each type of drug and material used, as well as half-lives.

2.2.5 Limited time on market

The project life will be 6 years until a new device with newer technology or generic options will

replace this current product.

3. Introduction

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Implantable drug delivery systems continue to be incorporated within various therapies ranging

from hormones, opioids, antibiotics to oncology applications. These systems have many benefits.

One benefit is that an implantable drug delivery device allows for the drug to be administered in

a specific site, without having to diffuse or transfer over various tissue or blood vessels. Another

main benefit is the implantable device’s ability to minimize potential side effects due to its ability

to specify dosage and to sustain release. This ability for sustained release contrasts injections and

pills in patients greatly allowing for more controlled specific treatment which can be essential

especially within oncology treatment. Furthermore, implantable drug delivery devices are less

burdensome to patients. Unfortunately, these systems currently on the market call for extraction

of the device and do not provide essential feedback about the drug delivery that is occurring.

Therefore, an alternative system is proposed. This system would be biodegradable and have no

need for extraction. It would allow for rapid to slow degradation of the device depending on the

application and would integrate into native tissue. Furthermore, this device would be

multifunctional and provide feedback about the condition or disease progression of the patient.

Overall, the goal would be to produce an implantable, dissolvable, multifunctional, drug delivery

devise that would have no adverse biological effect on the patient. This presents a unique and

desirable business opportunity.

The ideal location of the implantable device will be in the subcutaneous layer underneath the

skin. This is the best location as there is an excessive amount of blood vessels in this layer which

will allow for rapid absorption of the drug. The location in the body will depend on what type of

drug is being administered and what it is treating. For example, currently on the market are pain

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relief pumps which administer the desired drug directly into the spinal column fluid. Another

example is a birth control implant in the upper arm that lasts three years. Within the scope of this

drug delivery device, the capsule and sensor would biodegrade. Therefore, there would be no

need to surgically remove either of them. Once the sensor and/or capsule are degraded to the

point they are no longer functional then a new sensor and/or capsule could be implanted based

upon patient need. Within this specific business opportunity, the main drug that was focused on

was the hormones. Potentially, hormones would be one of the best-selling markets for this

device since in 2008 there were 15.5 million women in childbearing years (15-44) using

hormone contraception. Therefore it is estimated that this would be a good drug to introduce this

device with and potentially incorporate the device with other drugs into the market at a later

point.

4. Description of Base Case

4.1 Overall Product Description

The PLGA is a honey-comb structure with the ability to stack the microstructure. Stacking the

microchambers would allow a higher drug capacity depending on the treatment. Each

microchamber layer dimensions include “the thickness of the PGLA sidewall is 50 μm, and the

depth of the chamber is 300 μm and eight ribs have been added to improve the mechanical

strength. The bottom layer thickness of this PGLA microstructure is about 500 μm. The rib’s

width is 50 μm.” [Yang] I estimated each diameter to be 1500 μm. The total volume of the layer

is 5.3*108 μm3, the volume of the PLGA is 1.8*106 μm3 and the volume of the space that the

drug can occupy is 3.5*108 μm3. The volume of each microchamber space is designed so that as

the device degrades radially the same amount of drug will be released through time. This will

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provide the desired linear rate of release. Fig. 2 below shows the honey-comb microchambers

and how they are stackable.

Figure 2. Honey-comb microchamber.

The copolymer ratio will affect the degradability and rate of release of the drug. The half-life of

the PLGA copolymer (lactic acid (LA) and glycolic acid (GA)) ratio is shown in Fig. 3 below.

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Figure 3. Half-life of lactic acid and glycolic acid.

The graph shows if the copolymer ratio is 50/50, the half-life is the smallest. This means that the

capsule will degrade faster. The longest half-life would be 100% LA but the common ratio used

is 75/25 LA/GA. In Fig. 4 below shows an example of the percent of thyrotropin-releasing

hormone (TRH) left in the chamber based on the PLGA copolymer ratio. The y-axis is the

amount of TRH remaining in the PLGA structure.

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Figure 4. Rate or release based on different copolymer ratios.

This once again confirms that the slowest rate of release is 100% LA and the fastest is 50/50. As

stated before the common ratio is 75/25. Fig. 5 below shows the remaining percent of TRH in a

copolymer with the ratio of 75/25 but with differing molecular weights.

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Figure 5. Rate of release of a 75/25 copolymer ratio with different MW.

As you can see, the smaller the molecular weight of the polymer, the faster it degrades and the

faster the TRH is diffused. As well as the larger the molecular weight, the slower it degrades and

more TRH is left in the structure.

Figures 3, 4, and 5 were taken from Wako-Chemicals.

An in vitro experiment was done with the honey-comb microchamber design with a saline

solution and sugar powders. The saline solution is homologous to the subcutaneous fluid that

would degrade the microchamber and the sugar powder is homologous to the drug that would be

inside the capsule. Fig. 6 below shows the absorbance of the sugar powder into the saline

solution.

Figure 6. Absorbance of sugar powders in saline solution.

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Sample I has twice the amount of sugar powders as Sample II. With twice the amount of sugar

powder, there was almost twice the rate of absorbance. This proves that if the patient needed a

higher dosage, the amount of drug would need to be increased. This can be done by adding

microchamber layers. This also shows a fairly linear rate of release over time. A linear rate of

release is what is desired and the goal of the device. Fig. 7 shows how the chambers degrade in

this in vitro experiment.

Figure 7. Degradation of PLGA.

The sensor that would be combined with the PLGA honey-comb structure would be an optical

biosensor that uses fluorescence energy transfer. The sensor can also be made out of PLGA,

which is part of the reason it was chosen. With this sensor the drug delivery device will be able

to provide feedback. The optical device is designed so that the analyte flows through the sensor

and reversibly binds to an analyte binding agent (i.e. antibodies, drug receptors, and hormone

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receptors). The analyte analog (i.e. the drug) is marked with a donor chromophore and the

analyte binding agent (i.e. the drug receptor) is marked with an acceptor chromophore. The

absorption spectrum of the acceptor and emission spectrum of the donor overlap when the donor

and acceptor are put into close proximity by the binding of the analog and binding agent

[Christopher]. The acceptor then emits fluorescence. The intensity of the fluorescence signal

emitted correlates with the concentration of the analyte analog in the sensor. When the sensor

starts to degrade, the amount of chromophore will decrease; therefore the intensity of the

fluorescent signal will diminish. This will allow for the detection of when a new biosensor would

potential be needed. This fluorescence is read by a fluorimeter, which is a different device

outside of the skin. The fluorimeter shines light on to the sensor in the skin and the fluorescence

is reflected back to the fluorimeter. Then a series of functions produces a reading to give

feedback about the amount of analyte analog in the analyte. There is still a lot to learn about the

sensor and fluorimeter. The series of functions that happens in the fluorimeter would be a

potential area in which there would need to be more research. This area seems to fall under more

of an electrical engineering standpoint or physics, which are not our areas of expertise but we

could try to understand the basics of how it works. Another area that needs to be researched

further is how exactly the sensor in the skin will look / be designed as well as the external

fluorimeter.

The PLGA device and optical sensor will be implanted in the subcutaneous layer of the skin with

a 14 gauge hypodermic needle. Fig. 8 shows the size of this needle in comparison to a dime.

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Figure 8. Hypodermic implantation needle size.

This needle size is smaller than the needle used to implant a microchip in a dog. In terms of the

size of the needle, since the microchip for a dog is already acceptable, we believe that the 14

gauge will be acceptable to implant this device into a human, with little to no pain.

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4.2 Mass Transfer

As mentioned before, the structure is designed so as the chambers dissolve radially, the amount

of drug released from each chamber is the same, giving the ideal therapeutic treatment. The mass

transfer is based on the geometry of the chambers, and since there is little research on the

honeycomb structure, more information was not available on the quantitative analysis of the

mass transfer.

4.3 Assumptions

Assumptions include: the cost of the drug, $0.29/mg, based upon calculations from the price of a

generic hormone based upon mg sold, $450 per unit from the current implantable hormone

device for initial economic evaluation, a current competitor for this device on the market,

Implanon, and assuming that the utility costs will not exceed the leeway within the plant

overhead.

4.4 Discussion of Solution

This device fits all of the parameters needed; a linear rate of release, dissolvability, provides

feedback, and is less burdensome on the patient.

5. Base Case Manufacturing

5.1 Product Manufacturing Flow Diagram

The proposed flow diagram for both general products would be: synthesize drug delivery device,

implant device into patient, analyze results from devise, wait/induce biodegradation, and finally,

implant again if necessary based upon analysis. This is shown in the general block flow diagram

for making and implanting the drug delivery device in Figure 9.

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Figure 9. Overall block flow diagram.

“An optical mask was used to lithographically pattern the SU-8 insert-mold as shown in steps 1–

4. A thin layer of PDMS (polydimethylsiloxane) was then coated on the SU-8 micro patterns.

The PDMS layer is mechanically peeled off to obtain the final mold. This PDMS mold was then

used to fabricate the PLGA structures. Because PDMS is very flexible, it can be easily removed

from the coated PLGA without causing significant deformation of PLGA structures. Liquid

nitrogen may also be used to help to remove the PLGA structures from PDMS insert mold

because of the stress generated by dramatically lowered temperature. In addition, other special

materials may also be coated on the PDMS to reduce adhesion and make it easier to release the

PLGA structures in molding process.” [Yang] The steps that this process is referring to are the

steps shown in Fig. 10 below.

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Figure 10. Manufacturing processing of PLGA structure.

The flow diagram of the process is shown in Fig. 11 below.

Figure 11. Block flow diagram for manufacturing PLGA structure.

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Fig. 11 is a combination of our overall block flow diagram (Fig. 9) and the manufacturing

process of the PLGA structure (Fig. 10).

5.2 Major equipment

The major equipment for the manufacturing of the PLGA would be the UV-Lithography

machine, vacuum ovens and a DI water system.

5.3 Utilities requirements

The only utilities for manufacturing the PLGA would be water for the DI water system, and

electricity. These cost were assumed to be part of the plant overheard due to their low quantity.

6. Process Alternates

6.1 Silk MPA

The second technology investigated was that of the Silk MPA. The silk MPA is prepared by

micromolding techniques that result in a 100-μm think, free-standing silk reflector film. “The

dissolvable time of the silk MPA can be controlled based upon the degree of crystallinity during

the silk protein self-assembly process by regulating the water content within the film through an

annealing step” [4]. Figure 12 shows this multifunctional device. A within this figure displays

the reflectivity contrasted against the drug release. As shown, as the drug release continues

overtime, the reflectivity decrease, thus allowing for feedback on the device.

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Figure 12. Multifunctional Optical Device.

B displays the degradation of a Silk MPA over time. C displays the contrast in the shape of the

Silk MPA device when it is loaded with a drug as compared to the silk without the MPA. D

show that when the drug is put into a MPA its dissolvability is better controlled.

Testing of the distillation rate within the Silk MPA was also performed. The results demonstrated

the in vivo sustained release of a protein for 3 months, excellent biocompatibility, and the

biodegradation at a set time point of 3 months show in figure 13 [2].

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Figure 13. In vivo Sustained Release of Protein Drug B from Injectable Silk Formulation.

Furthermore, the sustained release of different drugs was studied in vitro from an injectable silk

formulation. Two types of drugs were studied, a peptide drug shown in figure 14, and a small

molecule drug shown in figure 15.

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Figure 14. In vitro Sustained Release of Peptide Drug from Injectable Silk Formulation.

Figure 15. In vitro Sustained Release of Small Molecule Drug from Injectable Silk Formulation.

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Both were found to have a general sustained release almost equal to zero, meaning that this

sustained release achieves its desired therapeutic window for long-term sustained drug delivery

which is a goal to equal zero.

The micro prism array allows for feedback on this device based upon a reflection signal off of

the silk reflector within the device. Figure 16 displays the schematics of the set for the

evaluation of the performance of the Silk MPA.

Figure 16. The schematic of the experimental setup for the evaluation of the performance of

the Silk MPA.

The Silk reflector work with “incoherent white-light illumination provided to the silk reflector

from a fixed height and a backscattering reflection probe is used to collect the response from the

same height and couple it to a spectrometer” [4]. This gives information about the condition of

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the drug delivery device therefore giving feedback about the condition of the targeted drug

deliver situation.

The Silk MPA is proposed to be implanted in a similar manner as the PLGA, but a much smaller

needle would be needed, which is currently available on the market.

Overall, the Silk MPA has great potential for a drug delivery device that would achieve all of the

goals of this project, but further investigation and testing would need to optimize this product

before this design to become feasible to a mass market application.

6.2 Silk MPA Manufacturing Process

A Silk micro prism array (MPA) is created from a production process that is seemingly not

difficult and is shown in figure 17.

Figure 17. Flow diagram for manufacturing of Silk MPA.

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First silk must be harvested and purified from Bombyx mori cocoons. The purification process

begins with the cocoons being boiled in a 0.02M aqueous solution of sodium carbonate for 30

minutes. Then, the resulting fibroin bundle is dried. Next, this bundle is dissolved in 9.3M

aqueous solution of lithium bromide at 60℃ for four hours. Then, the lithium bromide is

extracted with a water-based dialysis process over several days. Finally, the solution is

centrifuged and filtered with a syringe based micro-filtration. This process yields about 6.5 to 8

percent solution of silk fibroin. Silk fibroin is one of the main materials that will be used within

this process to create the Silk MPA. It is at this point where the drug is added to the silk fibroin

solution. Then the silk fibroin solution is cast onto a Microprism Master Mould (3M Scotchlite

Reflective Material – High Gloss Film). When this solution is being cast the thickness and

surface feature size can be controlled based upon the mechanically robust films of

thermodynamically-stable beta sheets that the silk can be easily form into [5]. These films are

formed “by simple casting of purified silk solution which crystallizes upon exposure to air”.

Furthermore, the ability for the Silk MPA dissolution rate is based upon the “variation of the

degree of crystallinity (β sheet content) introduced during material processing”. This distillation

rate can be set to instantaneous to years. In order to finish the Silk MPA, it is allowed to dry on

top of the Microprism master mould for 8-12 hours.

6.3 Silk MPA Economics

The economic basis for the Silk MPA was based upon current market prices for the raw material

needed including the mould needed to make the MPA.

The Price Summary for the Silk MPA device is as follows in Table 1.

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Table 1. Price Summary of Silk MPA.

Type of Cost Cost

FCI $6,000

Raw Materials 284 $/yr

Total Variable Costs 303 $/yr

Total Fixed Costs 7.4 M$/yr

Start Up $560

Revenue 22 M$/yr

NPV0 161 M$

NPV10 113 M$

IRR 5342%

Pay Back Period ~1 month

The type of costs show in table one will be further discussed within the economic section of this

report. To summarize the above table, the fixed capital investment is low, as is the raw materials,

the total variable costs, the total fixed costs, and the start-up amount. Overall, the revenue is

verily high, with a large net present value initially and after ten years. The internal rate of return,

which is typically used to determine if a business opportunity will be profitable, is extremely

high for this device. Furthermore, the payback period is very short. All of these above stated

reasons conclude to the fact that the manufacturing of this device is very economically feasible,

and therefore would make a good potential business opportunity worth pursuing.

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7. Permitting and Environmental Concerns

As far as we know, the only permits we would need would be in the form of a lease for the lab

we plan to rent in Massachusetts. We also don’t believe we would have any environmental

concerns as the device is biodegradable and there are no known harmful byproducts from

manufacturing the device.

8. Risk Management, Safety and OSHA Requirements

Overall, this proposed implantable drug delivery device poses very few risks. A few of these

risks include possible malfunctions within the device, possible non-effectiveness within specific

or alternative applications of this device, the potential rejection within the human of the device

body, law suits from similar device patents, and the fact that this device will be viable on the

market for about six years. Potential safety and OSHA requirements include the manufacturing

and shipping of this device. The manufacturing of this device will need to be sterile in order to

maintain these requirements. Furthermore, because continual exposure to harmful chemicals can

be dangerous, proper OSHA procedures, such as personal protective equipment, will need to be

instructed upon and used within facilities. Also, some chemical waste will be generated within

the manufacturing of this device, proper disposal of these chemicals, such as acetone, will need

to be performed. Overall, compliance to these governmental laws should not be difficult due to

the lack of environmental impact of the manufacturing of this device.

9. Project Economics

All of these economics are based on the breakeven point. In order to determine our fixed costs,

the following equations were used: Labor would equal 30 men/Shift at 20$/hr, Maintenance

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would be 4% FCI, Laboratory Cost would be 10% Labor, Plant Overhead would be 30% of

(labor, maintenance, lab), Taxes and Insurance would be 3% FCI, and Rent of Laboratory would

cost $3327/month from Emerging Tech Center in Woburn, MA. The labor assumption is that 30

men are divided with 10 laboratory workers and 20 salesmen/teaching hospitals how to implant

the device and read the feedback. After the breakeven point analysis was performed on this

economic evaluation, a sensitivity analysis was performed. Within this sensitivity analysis it was

determined that the optimal price per device was $150/unit, not the $450/unit as initially

calculated. This analysis is shown further in the following sections. Further break down of these

economics is show within the appendix.

9.1 Economic Basis

The price basis for the PLGA is as follows. From GFS Chemicals, the average price for lactic

acid is approximately 0.08 $/mL. From Wako Chemicals the average price for glycolic acid is

approximately 0.57 $/gram ($0.72/mL). Through calculations based on the ratio of 75/25 LA/GA

and the volume of PLGA per honey-comb layer, the approximate price of PLGA is 0.00013

$/layer. Calculation can be seen within the appendix.

After finding the fixed costs, variable costs and how much we were going to sell each unit for, a

breakeven analysis was performed. From those calculations, 24,872 devices to break even would

need to be sold to break even.

9.2 Price Summary

The Price Summary for the PLGA device is as follows in Table 2 based upon the $450/unit.

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Table 2. Price Summary of PLGA.

Type of Cost Cost

FCI 1.9 M$

Raw Materials 47,000 $/yr

Total Variable Costs 47,222.98 $/yr

Total Fixed Costs 8.4 M$/yr

Start Up $186,000

Revenue 11.2 M$/yr

NPV0 5.6 M$

NPV10 2.7 M$

IRR 28%

Pay Back Period ~1.5 years

To summarize the above table, the fixed capital investment is relatively low as compared to other

manufacturing plants, as is the raw materials, the total variable costs, the total fixed costs, and

the start-up amount. Overall, the revenue is high, with a decent net present value initially and

after ten years. The internal rate of return, is reasonable for this device. Furthermore, the

payback period is within reason.

To further progress the economic evaluation of this device a sensitivity analysis was performed.

This sensitivity analysis was based upon the price per units sold of this device, which was

assumed to be the most sensitive economic factor within the production of this device. Show

below are two figures that display the results of this sensitivity analysis.

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Figure 18. Selling Price Sensitivity Analysis Displaying IRR.

Figure 19. Selling Price Sensitivity Analysis Displaying Breakeven Units.

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As this sensitivity analysis displays in figure 18, the optimal price per unit where the net present

value initially and after ten year and the internal rate of return are the highest is at $150/unit.

The only factor stopping this from being a reasonable price is the number of units sold. At this

price per unit, 232,826 units would need to be sold in order to maintain the breakeven point,

shown within figure 19 at the maximum. In order to determine if this number is possible, the

Implanon was evaluated once again. The Implanon was initially introduced to the market in

1998. Over the course of the past 16 years, the Implanon has on average sold about 300,000

units per year. Therefore, this number of 230,000 units sold is plausible, but this value is highly

unlikely within the first year of manufacturing due to lack of knowledge about the device, etc.

Furthermore, a higher NPV and IRR could be obtained at a lower price per unit, but this higher

amount of units sold is unreasonable.

Overall, these above stated reasons conclude that the manufacturing of this device is

economically feasible, and therefore would be a feasible business opportunity.

10. Conclusions and Recommendations

Throughout this semester, the device that was determined to be the best device for the above

stated parameters was the PLGA device. Therefore, our goal, to design an implantable,

dissolvable, multi-functional drug delivery device, was achieved. The PLGA device was

generally the better device based upon a more logical economic profile, more information

available concerning this device including a better description of the transport from the chemical

within this device to the surrounding body, and less environmental stress due to all the products

need to manufacture this device are all man made. Furthermore, this PLGA device is proposed

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as the best implantable, dissolvable, multifunctional drug delivery device because of not only its

versatility, but because of its ability to be easily manufactured with very little cost.

11. Future Work

The future of this implantable, dissolvable, multifunctional drug delivery device is the in the

versatility of this device. Within this project, this device was only evaluated for the use of

hormones, because this device could be potentially mass manufactured. But this device holds the

potential for various devices including opioids, antibiotics, and oncological applications.

Therefore, in order to improve this device, the implication for these other drugs, and the

manufacturing of this device within these different environments would need to be investigated.

Also, as need technology is released, this device needs to be improved and upgraded in order to

meet the market demands and the technology present. Overall, this product has the potential to

be very versatile and improve the current market standards for implantable drug devices.

12. Acknowledgements

BioMeds would like to thank the following professors in their help with this project:

Dr. Joseph Holles

Professor John Myers

Dr. John Oakey

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14 Appendices

a. Detailed Cash Flow

i. PLGA

38

1. PLGA NPV Calculations

39

40

2. PLGA Price Calculations

41

ii. Silk MPA

42

b. Equipment List

43

i. PLGA Equipment

DI Water Unit - $935.30

UV-LIGA SU - $225,000

Vacuum Oven - $8,731

Silicon Wafers – S100,000

ii. Silk MPA Equipment

DI Water Unit – $935.30

High Gloss Film - $10.00, ebay

c. Sensitivity Analysis:

i. FC, FV (100)

44

ii. NPV (100)

45

46

47

iii. FC, FV (150)

48

iv. NPV (150)

49

50

v. FC, FV (200)

51

vi. NPV (200)

52

53

vii. FC, FV (250)

54

viii. NPV (250)

55

56

ix. FC, FV (300)

57

x. NPV (300)

58

59

xi. FC, FV (350)

60

xii. NPV (350)

61

62

xiii. FC, FV (400)

63

xiv. NPV (400)

64

65

xv. FC, FV (450)

66

xvi. NPV (450)

67

68

xvii. FC, FV (500)

69

xviii. NPV (500)

70

71

xix. FC, FV (550)

72

xx. NPV (550)

73

74

xxi. FC, FV (600)

75

xxii. NPV (600)

76

77

d. Sensitivity Analysis Graphs Data

78