Challenges and risk mitigation strategies for silicon oil problem existing in pre-filled syringes.

1. Silicone oil and Pre-filled Syringe
Challenges and Risk Mitigation Strategies
Presented by,
Erin Davis

2. OUTLINE
 Introduction
 Types of Pre-filled Syringes
 Challenges of Pre-filled Syringes
 Case study
 Alternatives
 Risk Mitigation Strategies
 Conclusion

3. Introduction
 A prefilled syringe is a unit dose medication of
parental drug to which a needle has been
fixed by the manufacturer
 Primary packaging
 Delivery system
 Prefilled syringes have actually been around
for more than two decades
 Used to package injectable drugs and diluents
 Vaccines, blood stimulants, therapeutic
proteins, erythroproteins, interferons, and
rheumatoid arthritis

4. Types of Pre-filled Syringes
Types:-
 Glass-based systems
 Plastic-based systems
 Glass prefilled syringes are of two types
Oil siliconised
syringes
•Direct contact of
rubber to glass
surface
•Higher break out
forces
•Chances of
contamination
Baked on silicone
syringes
•Provide consistent
coating of the glass
barrel
•Break out forces
stay low during
storage

5. Challenges
Design, manufacturing, quality, and choice of a pre-filled
syringe is critical in specific therapeutic area
Silicone oil an essential evil
 Commonly used silicon oil: Medical grade, Dow Corning 360
(DC-360)
 Lubricates the inner surface of glass pre-filled syringe
 Ensures functionality (easy plunger movement)
 Ensures the working of syringes even after longer storage
period
 Source of unwanted sub-visible particles that alter
sensitive proteins under certain conditions (protein/silicone
oil complexes or aggregate)

6. Challenges
 Migration of silicone oil off of the barrel and into
the drug formulation
 Slow movement
 Negative force performance
 Device failures
Effects
 Reduced drug efficacy
 Decreased immune responses
 Insufficient container siliconization
 Break-loose failure
 Extrusion-force measurement failure
 Insufficient needle pull-out forces
 Due to adhesive polymerization control

7. Challenges
 Sensitive proteins undergo heterogeneous
nucleation at silicone droplet surfaces
(adsorb / desorb)
 Irreversible conformation change
 Increased risk of protein aggregation

8. Case Study
 Particle differentiation between
proteinaceous and non-proteinaceous
particles (silicone-oil droplets)
 Micro-Flow Imaging technique used to
detect the aggregate
 Sub-visible particle analysis
 Particle formation evaluated using
polysorbate-20(PS-20) concentrations
 Protein aggregate due to agitation
increase smaller sub-micron droplets
Release of silicone oil droplets from syringes

9. Risk Mitigation Strategy
Quality by Design
 Quality target product profile (QTPP)
 Critical quality attributes (CQAs) and critical process parameters (CPPs)
Internal siliconization of glass vials
 Minimizes the interactions between the product and container
 Prevents high viscosity products on internal vial surface
 Provide prefect transparency
 Uniform silicone oil distribution to reduce silicone oil quantities
 Thermal fixation of the silicone oil (baked-on siliconization)
 Plastic-based silicone oil-free or low-silicone oil prefillable syringe systems

10. Risk Mitigation Strategy
 Gliding properties of the fluoropolymer coating on specially developed plunger
stoppers eliminate the need to siliconize plastic syringes
 Digital image processing :
 Inside surface of the syringe barrel is imaged
 Visualize typical siliconization surface structures

11. Alternatives
•Inert gas plasma cross-links the lubricant
•Provides stability without any complex reactive groups
•Can be used with standard inert silicone oil without any
additives
•plasma immobilized, inert perfluoropolyether based
lubricant
•Next-generation transparent solutions TriboFilm
Plasma Immobilized
(cross-linked)
Lubricants
•Syringes completely free of any lubricants
•Provide sufficiently low friction surface
•Restricted to plastic syringes and cartridges
•Laminate materials stiffens the elastomer closures
•Reduction in compressibility cause leakage
•Shortcomings : Design of the container & tight dimensional
tolerance
Laminated
Plunger

12. Conclusion
 Pre-filled syringes as unit dose medication is vital
 Siliconization is crucial to the efficiency of the entire system
 Lubrication is for optimal machinability performance
 RMS facilitate better quality and ensure regulatory compliance
 Robust risk management or mitigation strategy is fundamentally critical
 Innovative approaches ease the challenges

13. References
 https://tribofilmresearch.com/particle-risk-checklist-for-pre-filled-medical-device-projects
 https://www.ondrugdelivery.com/lubricious-coatings-reduce-silicone-oil-particle-levels
 http://www.biopharminternational.com/test-methods-and-quality-control-prefilled-syringes
 https://www.medicaltradefair.com/en/News/Future_of_Prefilled_Syringes:_Manufacturer_s_Per
spective_%E2%80%93_Challenges_and_Opportunities
 https://www.proteinsimple.com/mfi_overview.html
 http://www.jpionline.org/article.asp?issn=2230973X;year=2011;volume=1;issue=4;spage=200;ep
age=206;aulast=Makwana
 http://www.samedanltd.com/uploads/pdf/white_paper/1361284787_TP02040072_Reuter_sonder
druck_englisch2.pdf
 https://www.ondrugdelivery.com/next-generation-lubrication-solutions
 https://www.ondrugdelivery.com/risk-mitigation-performance-larger-volumes-drive-innovation