multilayer plastic vial & syringe with excellent oxygen … has developed a new plastic medical...

Multilayer Plastic Vial & Syringe

with Excellent Oxygen Barrier

Researcher

Haruka Okazaki

CPhI Worldwide InnoPack Speaker’s Corner24th October, 11:50 – 12:20

1

Mitsubishi Gas Chemical (MGC)

• Belonging to Mitsubishi Group

• Head Office: Tokyo, Japan

• Established in Jan.1918

• Net Sales: US$ 5.5 billion(On a Consolidated basis, Mar. 2017, US$1=\100)

• Employees: approx. 8000(On a Consolidated basis, Mar. 2017)

• Main Products

・ Methanol

・ Hydrogen Peroxide

・ Polycarbonate

・ Nylon-MXD6

・ Oxygen Absorber (AGELESS® )

etc.

Japan；

2 sales offices, 7 productions,

3 research centers

Overseas；

5 sales offices, 19 productions

2

Nylon-MXD6

• Polyamide Resin

• Features

-Good Gas-Barrier (O2, CO2, etc.)

• Applications

Nylon-MXD6

Injection Blow Molding Extrusion Molding

‣Soda Bottles ‣Beer Bottles ‣Food Packaging

3

AGELESS®

• Sachet Type of Oxygen Absorber

• Features-Prevents oxidation

-Preserves flavor and nutrition

• Applications-Used in Gas-barrier packaging

AGELESS®

Food ProductsMedical Products

Enclosed

MGC is a leading company in the field of

oxygen barrier material and oxygen absorber.4

Today’s Overview

✓ Features of Glass and Plastics

～Various good aspects of Plastics～

✓ Excellent Oxygen and

Water Vapor Barrier Ability of OXYCAPTTM

✓ Concept of OXYCAPTTM

～Two key technologies;

New Oxygen Absorbing Resin

& Multilayer Configuration～

✓ Technical Data of OXYCAPTTM

5

Today’s Overview

6










Glass vs Plastics

7

Glass Plastics (COP)※Cyclo Olefin Polymer

Oxygen Barrier Excellent(Permeation = Zero)

Poor

Water Vapor Barrier Excellent(Permeation = Zero)

Excellent(Permeation = very low)

Resistance to Breakage Poor Favorable

Inorganic Extractables Much Low

Organic Extractables Low Low

pH Stability Bad Good

UV Barrier Poor Poor

Transparency Excellent Excellent

Weight Heavy Light

Protein Adsorption Much Low

Disposability Difficult Easy

Today’s Overview

8










Plastic has poor oxygen and water vapor barrier

compared with glass.MGC has developed a new plastic medical container

with excellent oxygen and water vapor barrier.G

oo

d←

Oxyg

en

Barr

ier

→P

oo

r

Good ← Water Vapor Barrier → Poor

OXYCAPTTM ~OXYCAPTTM Vial & Syringe~

Oxygen and Water Vapor Barrier

9

Glass Plastic s(COP)※Cyclo Olefin Polymer

OXYCAPT™

Oxygen Barrier Excellent(Permeation = Zero)

Poor Excellent(Permeation = very low)

Water Vapor Barrier Excellent(Permeation = Zero)



Resistance to Breakage Poor Favorable Favorable

Inorganic Extractables Much Low Low

Organic Extractables Low Low Low

pH Stability Bad Good Good

UV Barrier Poor Poor Favorable

Transparency Excellent Excellent Excellent

Weight Heavy Light Light

Protein Adsorption Much Low Low

Disposability Difficult Easy Easy

OXYCAPT™

OXYCAPT™ has the best properties

both of Glass and Plastics container.

10

Today’s Overview

11










OXYCAPT™ Technology

◇New Oxygen Absorbing Resin

・Excellent Oxygen Barrier

・Retains Strength

・Low Extractables

◇Multilayer Configuration

・Improves the properties

・Co-injection molding

+

◇OXYCAPT™ Vial & Syringe・ Plastic containers with excellent oxygen barrier

・ Suitable for oxygen sensitive drugs

12

Oxygen absorbing resin has excellent oxygen barrier

as it absorbs oxygen from outside.

＜passive barrier resin＞＜oxygen absorbing resin＞

Oxygen Absorbing Resin

13

Example1. The oxidation of ether with transition metal

Example2. The oxidation of butadiene with transition metal

Existing oxygen absorbing resins’ problems

・High levels of low-molecular-weight extractables

・Lose structural strength

＋＋

Degradation!Existing OA resins’ film

after oxygen absorbing

Existing Oxygen Absorbing Resin

from other company

14

～Retain Strength～～Low Extractables～＜Tensile Strength Test＞

・Sample : The 10mm wide film.

・Measurement device : tensile testing machine

The films（SA：200cm2） were soaked in

100mL water and stored for 1week at 60℃

＜TOC Analysis＞

～Does not Degrade～


15

OXYCAPT™ Syringe- injection molding -

OXYCAPT™ Vial- injection blow molding -

Drug Contact & WV Barrier Layer

COP

Water Vapor(WV) Barrier Layer

COP

Oxygen Absorbing Layer(middle)

New Oxygen Absorbing (OA)

Resin

‣ 3 Layers（COP / New OA Resin / COP）‣ COP (Cyclo Olefin Polymer)

・Low Water Vapor Permeability

・Low Protein Adsorption

・Material of container for biological drug~OXYCAPTTM Vial & Syringe~

Multilayer Configuration

16

OXYCAPTTM has advantages of both new oxygen absorbing resin

and COP, and achieves glass-like gas barrier !

Today’s Overview

17










Features of OXYCAPT™ Vial & Syringe

<Features>・Excellent Oxygen Barrier

・Excellent Water Vapor Barrier

・Extremely Low Extractables

・Low Protein Adsorption

・High Transparency

・High Breakage Resistance

・Good pH Stability

・Easier Disposal than Glass

・Much Lighter than Glass

Water Vapor Barrier Layer(made of COP)

Drug Contact & WV Barrier Layer(made of COP)

Oxygen Barrier Layer

(made of Oxygen Absorbing Resin)

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Nest & Tab

0.000

0.001

0.002

0.003

0.004

0.005

0.006

0.007

0.008

COP Glass OXYCAPT™

Ox

yg

en

Pe

rme

ab

ilit

y(c

c/p

kg

/da

y/0

.21

atm

)

Stopper

Barrel wall

Tip Cap

0.000

0.005

0.010

0.015

0.020

0.025

0.030

0.035

0.040

COP COP/PA Glass OXYCAPT™

Oxyg

en

Perm

eab

ilit

y(c

c/p

kg

/day/0

.21atm

) Closure

Vial body

Oxygen Barrier

OXYCAPT™ has excellent oxygen barrier,

and can protect drugs just like glass.

＜Oxygen Permeability＞

10ml Vial

・Measurement device : MOCON OX-TRAN® 2/61

・Condition ： 23℃ / In 100%RH, Out 50%RH

1mL Long Syringe

Similar to Glass

Oxygen

Permeability from

barrel ≒ZERO

Extremely low

(Over 100 times

better than COP)

19

OXYCAPT™ keeps excellent oxygen barrier like glass.

＜The color of gel＞

No oxidation Oxidation

~ Before (0 day) ~

GlassCOP OXYCAPTTM

~ After (40℃, 6 months) ~

GlassCOP OXYCAPTTM

~ After (5℃, 18 months) ~

Storage Test with Oxygen Sensitive Gel

GlassCOP OXYCAPTTM20

Oxygen Concentration in Headspace

0.0

5.0

10.0

15.0

20.0

0 30 60 90 120 150 180

Co

nc

en

tra

tio

no

fO

xyg

en

[%

]

Storage Period [day]

Glass

COP

OXYCAPT™

10ml Vial

Headspace

（Zero oxygen

concentration）

O2

O2

<Test method>

- Filled with 5mL water

- Freeze degassing

→N2 gas introduction

→Freeze degassing again

⇒Zero oxygen concentration

in headspace

- Stored at 25℃・60%RH

- Analysis; oxygen analyzer

OXYCAPT™ keeps Zero oxygen concentration

in its headspace just like glass for a long time.

21

Water Vapor Barrier

OXYCAPT™ has excellent water vapor barrier like COP.

0.0000

0.0020

0.0040

0.0060

0.0080

0.0100

PET COP OXYCAPT™

WV

TR

(c

c/p

kg

/day)

0.0000

0.0002

0.0004

0.0006

0.0008

0.0010

COP OXYCAPT™

WV

TR

(c

c/p

kg

/da

y)

・Measurement device : MOCON PERMATRAN-W® 3/33

・Condition ： 40℃ / In 100%RH, Out 5%RH

10ml Vial 1ml Long Syringe

Similar

To

COP

Similar

To

COP

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＜Water Vapor Permeability＞

Organic Extractables

0

0.2

0.4

0.6

0.8

1

PET PP COP OXYCAPT™

TO

C（p

pm）

OXYCAPT™

100mL Vial

<Test method>

- Filled with 100mL water

- Stored for 3 month at 40℃- Analysis; TOC

OXYCAPT™ has low organic extractables like COP.

TOC：Total Organic Carbon

23

Extractable Study

10mL Vial

Extractables from OXYCAPTTM are same

to that from COP.

Materials Solvent GC-MS (for volatile impurity) LC-UV-MS (for non-volatile impurity)DI water

50% Ethanol

DI water

50% Ethanol

1% PS-80

5M NaCl

0.5N NaOH

0.1M Phosphoic acid

DI water

50% Ethanol

1% PS-80

5M NaCl

0.5N NaOH

0.1M Phosphoic acid

Glass Not detected Not detected

COP Not detected Not detected

OXYCAPTTM Not detected Not detected

<Test method>

・GC-MS and LC-UV-MS

・6 solvents recommended by BioPhorum Operations Group were selected.

・6 solvents : DI water, 50% Ethanol, 1% PS-80, 5M NaCl, 0.5M NaOH, 0.1M H3PO4

・Prepared 2mL-solvents were put in vials and stored at 40oC, 25%RH for 70 days.

・The duration is necessary to support 3 year storage time at 0 ℃.

-The studies were conducted by American CRO, Frontage Laboratories, Inc.(Exton, PA).

*ASTM F1980-07 “Standard Guide for Accelerated Aging of Sterile Medical Devices”24

Elemental impurity

10mL Vial

*These elements were selected based on ICH Q3D.

Extractables from OXYCAPTTM are same

to that from COP.

0

5

10

15

20

25

30

Li V Cr Co Ni Cu As Se Mo Ru Rh Pd Ag Cd Sn Sb Ba Os Ir Pt Au Hg Tl Pb

Extr

acta

ble

s [n

g /

vial

] Type 1 Glass VialCOP VialOXYCAPT Vial

<Test method>

・ICP-MS

・ 1% HNO3 recommended by CRO was selected

25OXYCAPT is suited to medical containers.

0

10

20

30

40

50

60

70

80

90

100

250 300 350 400 450 500 550 600 650 700 750 800 850

Tra

nsm

itta

nce

(%)

Wave Length(nm)

OXYCAPT™

COP

Glass TypeⅠ

Ultraviolet-Visible Absorbance

OXYCAPT™ shields UV light below 300nm.

⇒ OXYCAPT™ vial can protect UV-sensitive drug.

OXYCAPT™

10mL VialUltraviolet range

26

OXYCAPTTM Glass TypeⅠ

Test method1. 5wt% albumin solution was put into

vials and stored for 24h.

2. Dyed with “Coomassie brilliant blue

R-250” solution for 6h.

3. Rinsed with methanol 4 times.

Deeper Blue = more protein residue.

Protein Adsorption

27

OXYCAPTTM has low protein adsorption,

reducing unwanted residues of protein.

Laminated Stopper for OXYCAPT™ Syringe

<Feature of laminated stopper> Slight silicone-coat or Silicone-Free

Light break-loose and gliding force

Low extractables

Meet JP, EP, USP requirementJP 7.03／EP 3.2.9.／USP <381>

Sterilized by ETO

Inspection of endotoxin and bioburden

Chlorinated butyl rubber

Full-Laminated

(fluorinated film)

<Components of OXYCAPTTM Syringe>

OXYCAPTTM Syringe barrel

・Silicone-free

Tip types

・Luer Cone

・Luer Lock

Stopper

・PTFE-laminated butyl rubber

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Gliding Force of OXYCAPT™ Syringe

OXYCAPT™ syringe can minimize silicone oil and

decrease the break-loose force and glide force.

<Test method>

- 1 mL long Syringe

(27G×1” needle was attached)

- Filled with 1mL distilled water

- Stroke device : INSTRON® 5967

- Stroke rate : 200 mm/min

<OXYCAPT™① ~standard~>

※Gliding force increases gradually due to its inner draft angle.

Silicone-freeSiliconization

<OXYCAPT™② ~optional~>

Silicone-freeSilicone-free

29

0

5

10

15

20

0 10 20 30

Glid

ing

Fo

rce（

N）

Distance （mm）

OXYCAPT™ (stopper with silicone)

OXYCAPT™ (stopper without silicone)

OXYCAPTTM (stopper without silicone)

OXYCAPTTM (stopper with silicone)

Glass

Sample Availability

Type Size Sample Supply Remarks

Vial 2mL From April 2018 ISO 8362-1

6mL Already started ISO 8362-1

10mL Already started ISO 8362-1

Syringe 1mL Long Already started ISO 11040-6

2.25mL Already started ISO 11040-6

(10mL Vial for initial evaluation) (1mL Long Syringe for initial evaluation)

(Other Sizes)

(Samples with Nest & Tub)

※Sterilized by gamma-ray.※These samples are trial products, not guaranteed.※Only for compatibility testing (e.g. 6 months storage)

RTU Syringe RTU Vial

Sample supplying has been started.

If requested, custom-made containers are available.

Closure

Crimp-Seal

Lure Cone

and

Lure Lock

30

Product Area Requirement Status

Oxygen

Absorbing

Resin

USA USP 661.1(Physicochemical) Meet Requirements

USA USP 87/88 (Biological Test) Meet Requirements

USA Drug Master File No.27495

Europe EU-Directive(PIM) Completed

Europe EP (for Polyolefin) Meet Requirements

COP(for drug contact layer)

Japan JP7.02 (as Container) Meet Requirements

USA USP 661.1(Physicochemical) Meet Requirements

USA USP 87/88 (Biological Test) Meet Requirements

USA Drug Master File No.14084 & 27657

Europe EP (for Polyolefin) Meet Requirements

Vial

Japan JP7.02 Meet Requirements

USA USP661.2 In Progress (expected to be completed by 4Q 2017)

USA USP671 Meet Requirements

USA Drug Master File No.30669

Europe EP3.2.2.1 Meet Requirements

Syringe

Japan JP7.02 In Progress (expected to be completed by 4Q 2017)

USA USP661.2 In Progress (expected to be completed by 4Q 2017)

USA USP671 In Progress (expected to be completed by 4Q 2017)

USA Drug Master File In Progress (expected to be completed by 2Q 2018)

Europe EP3.2.2.1 Meet Requirements

- ISO13485 (Bulk) Meet requirements

- ISO13485 (RTU) In Progress (expected to be completed by 4Q 2017)

Regulatory works of bulk vial are expected to be completed by 4Q 2017.

All regulatory works are expected to be completed by 2Q 2018.

Regulatory Compliance

31

• MGC has developed “OXYCAPT™ Vial & Syringe”

for bio drugs.

• OXYCAPTTM Vial & Syringe have

greatest features of both Glass and Plastics.

Glass-Like oxygen and water vapor barrier,

Low levels of inorganic and organic extractables,

Low protein adsorption,

High resistance to breakage, etc.

• Custom-made OXYCAPTTM containers are

available.

Summary

32

MGC’s booth number is 42D71.We are looking forward to meeting you at our booth.

Thank you for listening.

multilayer plastic vial & syringe with excellent oxygen … has developed a new plastic medical...

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