The document discusses the significance of extractable and leachable testing in prefilled syringes (PFS) components, emphasizing their impact on drug safety and quality. It explains the differences between extractables and leachables, identifies PFS materials that may release these compounds, and outlines analytical techniques used for testing. The report highlights safety concerns related to protein aggregation and toxicological risks associated with chemical residues from syringe manufacturing and components.

1. IJSRD - International Journal for Scientific Research & Development| Vol. 1, Issue 3, 2013 | ISSN (online): 2321-0613
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Extractable and Leachable Testing In Prefilled Syringes Components
Prakash Patel1
Bharat Shah2
1, 2
L. D. College Of Engineering, Ahmedabad, Gujarat, INDIA
Abstract—In prefilled syringes (PFS) two words are namely
Leachable 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. LEACHING TYPE
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 the
container 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. HOW EXTRABLES AND LEACHABLE DIFFER
FROM EACH OTHER
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. WHAT IS PREFILLED SYRINGES?
“PFS (Pre-filled Syringes) is a pre-measured single-dose
ready-to-use injectable for parenteral drug delivery”
Why Extractable?
IV. MANUFACTURING PROCESS OF PFS?
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 but
migration of glass dissolution, pitting, stress, surface
weathering or erosion corrosion effects may lead to particle
formation.
B. Rubber Material
( Rubber Plunger, Luwertips, Needle Shield)
The plunger and Luwertips are Made from Bromobutyl
Formulations, 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 a
protein 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 a
lubricant 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 the
important of understanding silicone oil. Functionally
silicone oil is not a majoor concern for manual injections

2. Extractable and Leachable Testing In Prefilled Syringes Components
(IJSRD/Vol. 1/Issue 3/2013/0096)
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since a nurse r a doctor is capble of applying the necesaary
forces to push the plunger to end point. However a spring
can 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 particles
Ideally 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 tungsten
pin 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 and
storage.
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. ANALYTICAL TECHNIQUES FOR TESTING OF
EXTRACTABLE AND LEACHABLE
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 to
HPLC 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 leachable
investigation. Leachable from PFS may have contributed
safety concern related to protien aggrigation, particle
formation and toxicological risk factors. Identifying
extractable and leachable provides key information enabling
safety assesment that addresses toxicology and drug quality
impact for evaluating PFS
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