5/21/2018 Extractable and Leachable Testing In Prefilled Syringes Components

1/3

I JSRD - I nternational Journal for Scientifi c Research & Development| Vol. 1, I ssue 3, 2013 | ISSN (onli ne): 2321-0613

All rights reserved by www.ijsrd.com 788

Extractable and Leachable Testing In Prefilled Syringes Components

Prakash Patel1Bharat Shah

2

1, 2 L. D. College Of Engineering, Ahmedabad, Gujarat, INDIA

AbstractIn prefilled syringes (PFS) two words are namelyLeachable and Extractable are becoming a centre for

discussion in therapeutic protein produces to patients.

So understanding and testing of leachable and extractable of

prefilled syringe components is of utmost requirement in

parental drug delivery formulation development.

Keywords:Rubber Plunger, Leachable, Extractable, Parental

Drug delivery formulation development.

I. LEACHINGTYPE

Leachable are compounds that leach into the drug or

biological product from the container-closure system such

as the elastomeric or plastic components, or coatings of thecontainer and closure system.

Leaching is mainly as a result of direct contact with

the formulation under normal conditions of use.

Leachable are typically a subset of extractable, and

have potential to affect the product in various ways.

II. HOWEXTRABLESANDLEACHABLEDIFFER

FROMEACHOTHER

1) Different extracting conditions

2) Different time frames

Particular Extractable or Leachable can occur in more than

one component of the container

e.g. Calcium from both plastic resin and elastomer

III. WHATISPREFILLEDSYRINGES?

PFS (Pre-filled Syringes) is a pre-measured single-dose

ready-to-use injectable for parenteral drug delivery

Why Extractable?

IV. MANUFACTURINGPROCESSOFPFS?

Pfs components which cn contribute to Extractable and

Leachable .

A. Glass

Type I borosilicate glass is commonly used to make

prefilled syrynges abd it may contain various inorganic

oxides such as boron, silicon, calcium. Sodium, potassium,

iron oxide may not pose a f=direct toxicological risk butmigration of glass dissolution, pitting, stress, surface

weathering or erosion corrosion effects may lead to particleformation.

B. Rubber Material

( Rubber Plunger, Luwertips, Needle Shield)

The plunger and Luwertips are Made from BromobutylFormulations, needle Shields are made from a Latex Free

Polyisoprene Rubber Compounds.

The Rubber componets also comes in a Direct Conact with

Formulations,

e.g, Rubber Plunger Top surface is remain contact with a

different formulations or solvents so due to this storage

any residue forma plunger which can causes a

toxicoological effects to a formulations or may cause aprotein formation which is toxic in nature.

Mainly extractable: Nitrosoamine, vulcanising agents,

Plasticisers. Etc.

C. Silicone Oil

Silicone oil is applied to coat the barrel inside surface,

rubber plunger outer surface and Metal Canulla outer

Surface.

Silicone oil is polydimethylsiloxane and function as alubricant allowing the plunger guide smoothly within the

barrel to inject a Drug. As the deman for prefilled syrynges

and automated injection devices increases , so does theimportant of understanding silicone oil. Functionally

silicone oil is not a majoor concern for manual injections

5/21/2018 Extractable and Leachable Testing In Prefilled Syringes Components

2/3

Extractable and Leachable Testing In Prefilled Syringes Components

(IJSRD/Vol. 1/Issue 3/2013/0096)

All rights reserved by www.ijsrd.com 789

since a nurse r a doctor is capble of applying the necesaary

forces to push the plunger to end point. However a springcan provide a fixed amount of of forces and unanticipated

friction may cause the plunger to stall before complete drug

delivery.

Silicone oil is a inert insoluble in water it may

interact with in a formulation causing a protein

aggregation,droplets and particlesIdeally the silicone oil application process should

balance the need to minimise the quantity of silicone oil

also. The silicone oil distribution is non uniformely

distributed with least amount located near needle end of

syrynge.

D. Syrynge Pin-Tungsten Pin:

Lee obvious sources of PFS extractable are

contamination from tools that were used to manufacturer

and process syrynges. Glass syrynges are made from Cutting

and molding Glass tubing at high temprature. Heated glass

incontact with various processing tools like a Canulla Fix

sizes is made at more than 1,200 Degree C. now a tungstenpin is used to make a size for Canulla capillary, and at 150

>c a tungsten metal comes in contact with air and it cinvert

as Oxide as white substance residue in the syrynges.

These residue may survive the syrynge washing

step and may contact the drug upon syrynge filling andstorage.

E. Hypodermic Needle

The attached hypodermic needle is made if stainess steel.

Inorganic metal is used in stainless steel formulation such as

Fe, Cr, Mn,Ni and Mo may Leach from a Syrynge.and may

be a toxic in nature.

V. ANALYTICALTECHNIQUESFORTESTINGOF

EXTRACTABLEANDLEACHABLE

Analytical charactrerization and quantitation techniques

associated with organic and inorganic chemicals are

commonly used to analyse extractable/ leachable.

Gas chromatography mass spectrometry(GCMS), solid

phase micro extraction (SPME) GCMS, liquid

chromatography (HPLC), and nuclear magnetic resonance(NMR) spectrometry techinques are used to analyze unkown

organic extractable compounds. Inductively coupled plasma

mass spectrometry (ICPMS) can be used to identify and

quantitate inorganic metallic elements. Evaporative light

supplemental detection (ELSD) can be supplemental toHPLC and suitable for oligomers/polymers and non-

chromophores molecule analysis.

VI. CONCLUSION

To sum up ,PFS components and residues from processing

tools may leach organic and inorgenic chemicals into

formulated drugs. Leachable information is often not readily

available from the syringe manuftacturer promoting drug

manufacturers to initiate extractable and leachableinvestigation. Leachable from PFS may have contributed

safety concern related to protien aggrigation, particle

formation and toxicological risk factors. Identifyingextractable and leachable provides key information enabling

safety assesment that addresses toxicology and drug quality

impact for evaluating PFS

REFERENCES

[1] Novel Drug Delivery System: Extractable and

Leachable study in Drug Delivery System

Report2005,Autumn/Winter,47-49.

[2]

CDER/CBER Guidance for Industry: conainer ClosureSystem for Packaging Human Drugs.and Biologics-

Chemistry, MAnufacuring and Controls

Documentations. US Food And Drug Adminstration:Rockville, MD, April 1999: www.

FDA.Gov/Downloads/Drugs/Guidance C Ompliance

Regulatory Information/Guidances/UCM07055.Pdf.

[3] Jenke D.R. Evaluation of Model Solvent system for

assessing the accumulation of Container Extractable in

Drug Formulations. J. Pharm. Sci. 2001,224 (1-2).51-60[4] Jenke ,D.R. Linking Extractable and Leachables in

Container/closure applications.PDA J.Pharm

,Sci.Technol.2005.59 (4),265-281.

[5]

wang, Q, selectionn of Analytical Techniques forPharmaceutical leachables studies. Am Pharm, Rev.2005,8(6) . 38-44.

[6] Wakankar, A,A: Wang, J.Y: Canova-Davis,E; Ma S;

Schmalzing, D; Griego,J: Mibly,S; Martin-Moe, S; on

Developing a Process for Cundctiong Extractable and

leachable Assesment Of Components Used For Storage

of Bio-Pharmaceutical . J.Pharm Sci. 2010, 99(5) 2209-

2218.

[7] Nashed. Y: Torraca, G; Liu, D: Fujimori, K:Zhang, Z;

Wen, Z; Lee,H, Particle in a Glass Syrynges:

extractable /Leachable Cas Study.PDA J.Pharm. Sci.

Tech.2010,64 242-248.

[8]

Jiang , y; Nashed-Samuel. Y: Li,C.Liu, W.: Pollastrinji,J; Mallard, D; Wen. ZQ: Fujimori. K: Pallitto, M:

Donahue,L:Chu,G:Torraca,G:Vance,A:Mire-

sluis,T:Freund,E:Davis,J:NAhrhi,L.J.Pharm

Sci.2009,98 9(12),4695-710

[9] Hung G.W. Nunez L.J.: Autian J. Correlation of

Kinematic Parameters and thermal behaviour ofsegmented polyurathane elastomer with biological

response. J Pharm.Sci.1975.64,14921497.

[10]Danielle L. Advanced Innovations on a New Generation

of Prefilled syrynges. Cedar Cottage, New Timber

Place Lane, west Sussex, BN 6, United Kingdom: ON

drug Delivery Ltd. 2010

[11]

Walther, M: Rupertus, V: Seenmann, C; Bechcht, J;

Hormes, R; Swift, R.W. Pharmaceutical Vials With

Extremely High Chemical Inertness. PDA. J. Pharm,

Sci/ Technol, 2002 , 56( 3), 124-129.

[12]Jones L.S. Kafumann A. and Middaugh, C.R. Silicone

Oil Is Induced Aggregation of Proteins. J. Pharm

Sci.2005,94(4).918-927.

[13]Thirumangaathu , R. Krishanan, S. Ricci, M.S. Brems,

D. N.Randolph, T.W. and Carpenter, J.F.Silicone Oil-

and Agitation- induced Aggregation of a Monolcional

Antibody in Aqueous Solution. J. Pharm,Sci.2009,98(9)

[14]Lee. H; nashed- saumel, Y: Fujimori,k: Liu, D; Perez,

L.Tungsten Leaching from Prefilled Syrynges in

5/21/2018 Extractable and Leachable Testing In Prefilled Syringes Components

3/3

Extractable and Leachable Testing In Prefilled Syringes Components

(IJSRD/Vol. 1/Issue 3/2013/0096)

All rights reserved by www.ijsrd.com 790

Therapeutic Biologic Protein Products. Am.Pharm,

Rev.2006,9( 6) 3167-3181.[15]Deman ,J.M. Principles of food chemistry 3 rd Edition.

(1999) Aspen Publisher. ISBN: 0-8342-1234-X,131-

132.

[16]Thompson, I : New-Generation Autoinjector

Completing the scale of Convenience for self-

injection.