Good Laboratory Management:

Means compliance with the correct regulations for each individual study…..

EPA “Good Laboratory Practices…..

40 CFR 160 Federal Insecticide, Fungicide and Rodenticide Act [FIFRA]

40 CFR 792 Toxic Substances Control Act [TSCA]

Minor differences do exist between EPA and FDA “Good Laboratory Practices…..

Difference from FDA….Test System Care Facilities…160.43…

marine test organismsfreshwater test organismsplants [field studies]

Minor differences do exist between EPA and FDA “Good Laboratory Practices…..

Important difference is 40 CFR 160.12:

Statement of compliance or non compliance….

40 CFR 160.12: Statement of compliance or non compliance

Application must contain a statement signed by the applicant, sponsor, and SD that

(a) study was conducted according to 40CFR160 or

(b) describe in detail all differences between the practices used in study and those required..or

(c) a statement that the study was not conducted in accordance to 40CFR160

40 CFR 160.17: Effects of non- compliance

Submission of a statement required by 160.12 which is false may…lead to criminal prosecution

Civil Penalties

High Level GLP Violations

Failure to notify contractors of GLP applicability

Failure to keep personnel records

Failure to designate a Study Director

Failure to assure existence of a QAU

Failure of QA to perform inspections and maintain records

Failure to maintain SOPs

Civil Penalties cont.

High Level GLP

Failure to follow SOPS without proper authorization

Failure to characterize test materials

Unauthorized protocol deviations

Failure to record raw data; failure to retain raw data

Falsification of raw data

EPA Quality Assurance Project Plan

Be Aware of all regulations….

Especially the regulations for studies that your laboratory is conducting !!!!

Be a web warrior…

Other regulations ….

ISO [International Organization for Standardization] is the world’s largest developer of standards

What are ISO 9000 standards….

A collection of formal International Standards, Technical Specifications, Technical Reports, Handbooks and web based documents on Quality Management and Quality Assurance

www.iso.org

ISO is a network of the national standards institutes of 156 countries

A Central Secretariat in Geneva, Switzerland….that coordinates the system

One member per country

International standardization began in the electrotechnical field..

International Electrotechnical Commission [IEC] established 1906

In 1946 delegates from 25 countries ..created a new international organization

“to facilitate the international coordination and unification of industrial standards”

This new organization ISO officially began operations in 1947

When the large majority of products or services …..

Conform to International Standards, a state of industry wide standardization can be said to exist.

This is achieved through consensus agreements between national delegations representing all the economic stakeholders concerned…..

• suppliers

• users

•government regulators

• consumers

Agreement on specifications and criteria to be applied consistently in the ….

• manufacture and supply of products

• testing and analysis

• classification of materials

• terminology

• provision of services

So……

International Standards provide a reference framework or a common technological language between suppliers and their customers which facilitates trade and the transfer of technology

Benefit sBusinesses….

• can base development of their products and services on specifications that have acceptance in their sectors

• means businesses that use ISO standards are increasingly free to compete on many more markets around the world

Customers

• compatibility of technology

• brings an increasingly wide choice of offers

• benefit from the effects of competition among suppliers

Governments

• provide the technological and scientific bases underpinning health, safety and environmental legislation

Trade Officials

• Negotiating the emergence of regional and global markets…..creates “a level playing field” for all competitors on those markets

• ISO standards are the technical means by which political trade agreements can be put into practice

ISO 10993 Biological Evaluation of Medical Devices

• 10993-1 “ Guidance on Selection of Tests

• 10993-2 “Animal Welfare Requirements

• 10993-3 “Tests for Genotoxicity, Carcinogenicity, and Reproductive Toxicity”

• 10993-4 “ Selection of Tests for Interactions with Blood

ISO 10993 Biological Evaluation of Medical Devices

• 10993- 5 “ Tests for Cytotoxicity—In Vitro Methods”

• 10993-6 “ Tests for Local Effects after Implantation”

• 10993-7 “ Ethylene Oxide Sterilization Residuals”

• 10993-9 “ Degradation of Materials Related to Biological Testing”

ISO 10993 Biological Evaluation of Medical Devices

• 10993- 10 “ Tests for Irritation and Sensitization”

• 10993- 11 “ Tests for Systemic Toxicity”

• 10993- 12 “Sample Preparation and Reference Materials”

ISO 10993-1

Excellent guidelines for considering the safety of medical devices…

Materials should be characterized to provide an understanding…

of formulation

potential impurities

extractables

……to provide the basis for specifications

ISO 10993-1

Testing should be conducted according to good laboratory practices and evaluated by competent informed persons

Full experimental data should be made available to reviewing authorities

All relevant data, including information from nonclinical sources, clinical studies and postmarket experiences, should be taken into account when evaluating a device

Other regulations ….

OECD…Organization for Economic Co-operation and Development

What is the OECD?

• An Organisation of 30 member countries committed to democracy and the market economy

• A provider of comparative data, analysis and forecasts

• So that governments can:

- compare policy experiences

- seek answers to common problems

- identify good practice

- co-ordinate policies

OECD Member Countries

An organisation with global reach

Working with countries around the world

The OECD’s mission

Article 1 of the OECD Convention:

• Support economic growth• Boost employment • Raise living standards • Maintain financial stability• Assist other countries’ economic

development• Contribute to growth in world trade

Our environment

• Make markets work for a healthier environment

• Use science and technology to benefit people everywhere

• Cut wastage and pollution

Economics and trade

• Analyse and publish comparative data• Produce forecasts• Develop policies for growth and stability• Foster open markets• Encourage expansion of financial services• Promote cross-border investment• Share best practices

Social cohesion

• Ensure equal access to education for all

• Promote effective and accessible health systems

• Fight social exclusion and unemployment

• Bridge the “digital divide“ between rich and poor

Governance• Promote effective public administration• Encourage companies to run their

affairs better• Ensure transparent and fair tax systems • Foster fair competition • Fight corruption and money-laundering• Promote high ethical standards• Encourage citizen-participation in

policy-making

The OECD Secretariat

• Two official languages: English and French

• Staff members are international civil servants

• No quota system for national representation

• 2300 staff at Paris headquarter

Working with governments

• Sharing information and experience • Country and region-based co-

operation programmes• Peer review and surveillance

Working with civil society • Consulting with business

represented by the Business and Industry Advisory Committee

• Consulting with labour

represented by the Trade Union Advisory Committe

• Expanding relations with civil society• Making information available to the public

on www.oecd.org

Social cohesion

• Helping to ensure equal access to education for all

• Promoting effective and accessible health systems

• Fighting social exclusion and unemployment

• Bridging the “digital divide” between rich and poor

Our environment • Making markets work for

ecologically and economically sustainable development

• Harnessing science and technology in the service of citizens in all countries

• Strengthening decision-making to avoid wastage and pollution

Governance• Promoting good governance at all levels

of government and corporate activity

• Ensuring transparency and fairness in tax systems and competition rules

• Fighting corruption and money-laundering and promoting high ethical standards

• Supporting accountability and encouraging citizen-participation in policy-making

Some OECD achievements• DAC Guidelines for Poverty Reduction• OECD Model Tax Convention• OECD Anti-Bribery Convention• OECD Principles of Corporate Governance• OECD Guidelines for Multinational Enterprises• Export Credit Arrangement• OECD Guidelines for Conflict Prevention• OECD Chemicals Test Acceptance Agreement• OECD Chemical Hazard Classification System• OECD GM Crop Identification System

OECD Quality Assurance and GLP

Web site ….OECD.org

Quality Control

Quality Assurance

Validation

Verification

Quality Control:

Planned activities designed to produce a quality product ..

• Tools a scientist uses to measure accuracy and precision, and reduce variability

• Assuring that calibration procedures prove equipment accuracy

• Assuring equipment is reliable and gives reliable data

Quality Control:

• Verifying all transcribed data as accurate

• Assuring protocol required items are documented in data

• Assuring data stands alone; enough detail is available when needed; calculations are correct

• Assuring that data are complete, easy to read and follow

•Assure that checklists are dated and

initialed

Quality Assurance:

Activities designed to ensure that quality control procedures are functioning as intended

• Assuring protocols are followed

• Assuring deviations are documented and reported

• Assuring personnel are property trained

• Assuring that equipment is as specified in the protocol

Quality Assurance:

• Assuring management that systems are functioning as intended

• Assuring that study events are adequately documented

• Assuring that the final report ACCURATELY reflects the raw data

QA Issues

Validation: The action of proving that a procedure, process, system, equipment, or method works as expected and achieves the intended result over time.

QA Issues

Verification: A one-time process completed before the test system is used. Requires determination or confirmation of the test performance characteristics, including sensitivity, specificity, and where appropriate, the predictive values, precision and accuracy of the test.