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Arthrex requires suppliers to validate the special processes, both in-house and outsourced, that they plan to perform for Arthrex. In accordance with ISO 13485:2016 and 21 CFR Part 820, this includes any process in which the resulting output cannot be or is not verified by subsequent monitoring or measurement and, as a consequence, deficiencies become apparent only after the product is in use.

These processes may include but are not limited to:

  • Anodizing
  • Brazing and welding
  • Cleaning (in process or final)
  • Electropolishing
  • Gluing
  • Heat treating
  • Labeling
  • Painting
  • Final packaging
  • Nonsterile or sterile barrier packaging
  • Passivation
  • Sterilization
  • Coating

Validations shall follow the Installation Qualification (OQ), Operational Qualification Q), and Performance Qualification (PQ) formats and shall be conducted using statistically valid techniques that take into consideration the product risk associated with that process’s output. All other equipment that is not considered a special process still requires IQ and OQ.

Arthrex considers final cleaning to be any finishing manufacturing process that is intended to provide medical devices that are physically and biologically clean. Final cleaning processes shall be the final manufacturing process performed, with the exclusion of subsequent assembly, packaging, and sterilization processes. Examples include passivation, anodizing, electropolishing, etc.

Products that are final cleaned must meet the device cleanliness requirements shown on the following page.

 

Microbiological and Chemical Testing Specifications

Notes

Category

Test

Test Method/ Standard

Acceptance Criteria

Minimum Sample Requirement

Instrument

Implant

 

 

 

Physical/Chemical

Particulate

USP <788>

Device extraction (automatic, HIAC ROYCO), STER 800-02-1989 R1

10 μm <24,000

per device

5 devices

 

 

25 μm <4000

per device

Heavy Metals

Total content – migration in water (72 hours at 50° C per ISO 10993-12), followed by microwave digestion and ICP/MS analysis

Heavy metal profile below established margins of safety

2.6 g

 

 

Volatile / Semivolatile Compounds

Migration in

n-Hexane/IPA/

water/ (72 hours at 50° C  per ISO 10993-12),

followed by GC/MS analysis including headspace for water

Extractable/ leachable profile below established margins of safety

2.6 g per extract

X

(3 extracts) VOC – Water SVOC – Water SVOC – Hexane

X

(4 extracts) VOC – Water

SVOC – Water SVOC – Hexane SVOC – IPA

Nonvolatile Compounds

Migration in

n-Hexane/IPA/

water/ (72 hours at 50° C  per ISO 10993-12),

followed by LC/MS analysis

Extractable/ leachable profile below established margins of safety

2.6 g per extract

New polymers/plastics that have not been previously tested could require additional nonvolatile testing

 

 

 

Biological

Cytotoxicity

ISO 10993-5

MEM elution method

No cytotoxic grade can be greater than 2 on a scale of 0 to 4

Surface area of 60 cm2

Chemical characterization can supersede cytotoxicity testing for postdesign products

Bacterial Endotoxin (BET)

USP <85>

Bacterial endotoxin test: kinetic chromogenic method

<20.0 EU/device spike recovery between 50% and 200%

3 devices

 

 

Bioburden With Recovery

ISO 11737

Aerobic/fungal with inoculated recovery

<1000 CFU/device

recovery 50% (approximate target)

5 devices – bioburden 3 devices – recovery

Due to the variability of design, materials, manufacturing processes, etc, it is not always required to obtain 50% recovery efficiency (RE). Considering the data used for device cleanliness assessments (eg, bioburden screening), a lower RE would cause higher bioburden worse- case condition. Therefore, a lower RE would be a conservative estimate for this bioburden data. If bioburden RE fall below the 50% target, attempts may be made to improve the recovery efficiency. However, attempts for RE are not always required based on the use of the data.