International Organization for Standardization

Forms a bridge between public and private sectors

ISO

ISO 10993 Published in 1995 Series of standards for biological evaluation of medical devices… 20-part structure

ISO 10993-1 Framework for planning a biological evaluation Evaluation of existing data and identification of gaps Assessment of biological safety

ISO 10993-1

Preference for: a. In vitro models b. material / chemical

characterization

ISO 10993-1

Device categories a) surface, external

communicating and implant b) contact mode c) duration of contact

ISO 10993-1

Framework for a biocompatibility testing program Not a formal checklist

ISO 10993-18 Materials directly influence biocompatibility

a) surface chemistry and topography

b) extractable chemical compounds

c) particulates

ISO 10993-18 Equivalence of material Predict biological response Screening new materials Evaluate manufacturing process

Biocompatibility Testing of PPM’s Products

Device Category: Surface Device

Cytotoxicity Sensitization Irritation Acute systemic toxicity

Cytotoxicity

ISO 10993-5 In Vitro test Ideal for screening Agar Diffusion

Agar Diffusion Test

FDA Standard Quantitative test for cytotoxicity (ISO 10993-5) MTT Cytotoxicity In Vitro test Extract of the material

MTT Cytotoxicity

Sensitization ISO 10993-10 In Vivo Test Reactions are delayed, not localized and dose independent

Kligman Maximization Guinea pigs Day 0: Intradermal injection Day 7: Topical at same site Day 23: Topical at new site Days 23 – 25: Scored ISO 10993 scoring system

Irritation

ISO 10993-10 In Vivo Test Single exposure Reaction is immediate

Intracutaneous Injection

Rabbits Direct or extracts and control materials Scored over 72 hr period ISO 10993 scoring system

Systemic Toxicity

ISO 10993-11 Toxic effect:

a. distant from exposure site b. biological systems

Acute Systemic Injection

Mice Single intravenous and/or intraperitoneal injection Observed over 72 hr period Compared with controls

Material-Mediated Rabbit Pyrogen

Rabbit Single intravenous injection Body temperature: 30 min. intervals for 3 hour period Temp. increase limit: 0.5 ºC

Summary

Biocompatibility is vital PPM evaluates potential toxicity according to ISO 10993, parts 5, 10 & 11

Thank You

Questions?

George Paleos gpaleos@pittsburghplastics.com