Tolerance stack-up analysis is an invaluable tool for designing and verifying devices (e.g., prefilled syringes, autoinjectors). However, relying solely on tolerance stack-up analysis may not be sufficient in certain scenarios. Consider, for instance, the sterile seal created by the rubber plunger stopper against the barrel of a syringe.

When the plunger stopper is placed within the barrel, the rubber stopper undergoes compression. This compression generates the pressure to form a sterile seal. Figure 1 illustrates a compressed rubber stopper inside a syringe barrel. The color gradient (red, green, blue) in the figure represents the varying levels of stress (or pressure) exerted on the rubber stopper. This visualization helps in understanding the distribution of pressure, ensuring that the seal is effective and maintains sterility.

Employing such detailed analyses alongside tolerance stack-up helps in accurately predicting the performance and reliability of the sealing mechanism, thereby ensuring the overall functionality and safety of the medical device.

Example: Worst Case Tolerance Stack-up Analysis (Interference Fit Between Rubber Stopper and Syringe Barrel)

Specifications:

• Outer diameter of rubber stopper: 6.60 mm ± 0.1 mm
• Inner diameter of syringe barrel: 6.45 mm ± 0.1 mm

Analysis: In the worst-case scenario for a sterile seal, the weakest contact pressure arises from the combination of the widest syringe barrel and the thinnest plunger stopper.

Calculation:

• Interference fit to provide the weakest contact pressure: Interference fit = (widest syringe barrel−thinnest plunger stopper) / 2 = (6.55 mm−6.50 mm) / 2 = 0.025 mm

Is it acceptable to maintain product sterility?

To determine acceptability, the contact pressure should be calculated. This can be challenging to determine experimentally due to complexities in sample preparation and contact pressure measurement. Finite Element Analysis (FEA) can play a crucial role in this scenario.

FEA Main Inputs:

1. Individual part drawings and assembly drawing
2. Material properties (e.g., stress-strain model, Poisson’s ratio, volumetric compression)
3. Meshing
4. Boundary conditions

Using FEA, the contact pressure can be determined for various scenarios, including target and worst-case dimensions.

• Target Dimensions:
  • Rubber compression: 0.075 mm
  • Resulting pressure: More than 1 MPa
• Worst Case:
  • Rubber compression: 0.025 mm
  • Resulting pressure: Several hundred kPa

Next Steps: A study should be conducted to determine the acceptable pressure for maintaining a sterile seal. Research suggests that a contact pressure of approximately 0.6 MPa is effective for justifying a sterile barrier. Supporting studies, “Air, Helium, and Water leakage in Rubber O-ring Seals with Application to Syringes” (Tribology Letters, 2022), provide valuable insights into the relationship between contact pressure and leakage.

By leveraging FEA and empirical data, the design can be optimized to ensure that the sterile seal is maintained even under worst-case conditions, thereby ensuring the safety and reliability of the syringe system.