ISO 10993-1 “THE EARLY YEARS”

JAMES M ANDERSON, MD, PHDDISTINGUISHED UNIVERSTIY PROFESSOR

DEPARTMENTS OF PATHOLOGY, BIOMEDICAL ENGINEERING, AND MACROMOLECULAR SCIENCE

CASE WESTERN RESERVE UNIVERSITYCLEVELAND, OHIO

DISCLOSURES

• AD HOC CONSULTANT FOR CR BARD, INC.

• CONVENER FOR ISO 10993-1 (1987-2019)

• AD HOC CONSULTANT FOR MEDTRONIC CARDIOVASCULAR

• AD HOC CONSULTANT FOR DURECT, INC.

CONTRIBUTORS

Raju Kammula Jack Lemons Don Marlowe Jennifer Good Jeremy Tinkler Jon CammackArne Hensten Arthur BrandwoodDavid Mueller

“EARLY PLAYERS”

Don Gibbons Paul UpmanStephen Perren Richard WallinEd Muller Roger DabbahSharon Northrup Emanuel HorowitzMarie-Francoise HarmandPaul Didisheim Robert PryzgodaDan McLain A. Nakamura

ISO/TC 194 WG 1

• FDA TOXICOLOGY SUBGROUP SEPT., 1984(510K, PMA, IDE)

• TRIPARTITE BIOCOMPATIBILITY GUIDANCE SEPT., 1986

• PFORZHEIM, W. GERMANY 1989

• LONDON, UK JAN 31-FEB 1 1990

• ISO 10993-1 1992

EARLY CHAIRS, ISO/TC 194

STEPHEN PERREN, SWITZERLANDLAWRENCE HECKER, USA

EARLY FOUNDATIONS1961 JOHN AUTIAN PLASTICS: USES AND PROBLEMS IN

PHARMACY AND MEDICINE; AM J HOSP PHARM; 18: 329 (1961)

1965 USP BIOLOGICAL TESTS FOR PLASTIC CONTAINERS

1976 ADA GUIDE TO DENTAL MATERIALS AND DEVICES;CHAPTER 14; RECOMMENDED STANDARD PRACTICES FOR BIOLOGICAL AND CLINICAL EVALUATIONS

1979 BS 5736-1 EVALUATION OF MEDICAL DEVICES FOR BIOLOGICAL HAZARDS; PART 1: GUIDE FOR THE SELECTION OF BIOLOGICAL METHODS OF TEST

1981 BS 5736-2-11 SPECIFIED TEST METHODS

1982 ASTM F748 GENERIC BIOLOGICAL TEST METHODS

1985 ISO TC-150 BIOCOMPATIBILITY TESTS (VERTICAL STANDARDS: SPECIFIC DEVICES)

1986 TRIPARTITE BIOCOMPATIBILITY GUIDANCE USA (FDA), UK (BSI), CANADA

EARLY ASTM BIOCOMPATIBILITY STANDARDS AND METHODS

• F561 1978 Retrieved Implant, Tissue, and Fluid Analysis

• F619 1979 Extraction of Medical Plastics

• F719 1981 Skin Irritation – RABBITS

• F720 1981 Contact Allergens – GUINEA PIGS

• F748 1982 Generic Biological Test Methods

• F749 1982 Intracutaneous Injection – RABBITS

• F750 1982 Systemic Extract Injection – MICE

Intravenous or Intraperitoneal

• E756 1982 Hemolysis Assay – Extract and Direct Contact

• F763 1982 Short-Term Screening of Implant Materials

Muscle Implants – 7 and 30 Days

RATS, RABBITS, OTHER ANIMALS

• F813 2001 Direct Contact Cell Culture

• F895 1984 Agar Diffusion Cell Culture

• F981 1986 Long-Term Screening of Implant Materials

Muscle and Bone Implants – 12, 26 and 52 Weeks

RATS, RABBITS AND OTHER ANIMALS

• E1262 1988 Gene Mutation Assay, Cell Culture

ASTM F748 Generic Biological Test Methods - 1982

• Cell Culture Cytotoxicity

• Sensitization

• Irritation

• Systemic Injection (Acute Toxicity)

• Blood Compatibility

• Hemolysis

• Complement Activation

• Pyrogenicity

• Short-Term Implants

• Long-Term Implants

• Genotoxicity

• Carcinogenicity (2x2x2)

• Immunotoxicity

ISO TC 194 WG 1 - TIMELINE

• 1987 WASHINGTON, D.C.• 1988 NICE, FRANCE• 1989 LONDON, U.K.• 1990 LONDON, U.K

OSLO, NORWAY (ARNE’S 50TH BIRTHDAY)BOURDEAUX, FRANCE

• ??? ZERMATT, SWITZERLAND• 1996 STOCKHOLM, SWEDEN

• 2003 (04?) TROMSO, NORWAY• 2005 UTRECHT, NETHERLANDS• 2006 CHICAGO, USA• 2015 LUND, SWITZERLAND

DRASTIC CHANGES BETWEEN 1997 AND 2006 (DIS)

• 1997 – NO “RISK ASSESSMENT” ANNEX

NORMATIVE – BIOLOGICAL EVALUATION TESTS

INFORMATIVE – ANNEX B – FLOW CHART

NO ANNEX ON “LITERATURE REVIEW”

• 2006 – RISK ASSESSMENT (MANAGEMENT) – ANNEX B

ANNEX B – ISO 14971 + OVERALL RESIDUAL RISK/BENEFIT EVALUATION - OUTLINE

NORMATIVE – FLOW CHART

INFORMATIVE – BIOLOGICAL EVALUATION TESTS

ANNEX C – LITERATURE REVIEW

ISO 10993-1• 1992 FIRST EDITION

• 1997 2ND EDITION

• 2003 3RD EDITION

• 2009 4TH EDITION

• 2018 5TH EDITION (REVISION STARTED IN 2015, LUND, SWEDEN)

ISO/DIS 10993-23

6. IN VITRO IRRITATION TESTS

6.2 IN VITRO RECONSTRUCTED HUMAN EPIDERMIS (RhE) MODEL

CELL VIABILITY – MTT TEST

CELL ACTIVITY – IL-1α ASSAY

STANDARDS ARE ALWAYS EVOLVING AND CHANGING AS NEW TECHNOLOGIES AND

ASSAYS BECOME AVAILABLE

A MAJOR GOAL IN STANDARDS DEVELOPMENT IS THE REDUCTION OF THE USE OF ANIMALS AND REPLACEMENT BY IN

VITRO METHODS

“THE ONLY CONSTANT IS CHANGE”

-WINSTON CHURCHILL

There are lies, damned lies and statistics

Facts are stubborn, but statistics are more pliable

-Mark Twain