Major Advisor : Dr. K. JayakumarSpeaker : Amol R. Padol

CREDIT SEMINAR-I

INTRODUCTIONINTRODUCTION

OECD ???o an intergovernmental organisation.

o Representatives of 30 industrialised countries in North America, Europe, Pacific and the European Commission.

o To co-ordinate and harmonize policies, discuss issues of mutual concern, and work together to respond to international problems.

o Environmental Health and Safety Division.

o The Principles of GLP have been developed to promote the quality and validity of test data used for determining the safety of chemicals and chemical products (Schechtman, 2007)

Good Laboratory PracticeGood Laboratory Practice

o A quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

(OECD/ENV/MC/CHEM,1998)

o Its principles are required to be followed by test facilities carrying out studies to be submitted to national authorities.

o Common principles for GLP facilitate the exchange of information and prevent the emergence of non-tariff barriers to trade.

(Berend, 2002)

o The issue of data quality has an important international dimension.

o If regulatory authorities in countries can rely on safety test data developed abroad, duplicative testing can be avoided.

HISTORYHISTORY

o The GLP regulations for non-clinical laboratory studies published by the US-FDA in 1976 (Baldeshwiler, 2003).

o The OECD Principles of GLP were first developed by an Expert Group on GLP established in 1978 under the Special Programme on the Control of Chemicals.

o Principles of GLP were adopted by the OECD in 1981.

o Expert Group was established in 1995 to develop a proposal to revise the Principles of GLP.

o The Revised OECD Principles of GLP were reviewed in the relevant policy bodies of the Organisation and were adopted by Council on 26 November, 1997.

o Indian GLP Compliance Monitoring Authority - April, 2002.

SCOPESCOPE

Principles of GLP should be applied to the non-clinical safety testing of test items contained in, Pharmaceutical products Pesticide products Cosmetic products Veterinary drugs Food and feed additives Industrial chemicals.

o Test items: synthetic chemicals, natural or biological origin and, may be living organisms.

o Safety studies covered by the Principles of GLP include work conducted in the laboratory, in greenhouses, and in the field (Jena et al ., 2009)

o Principles of GLP apply to all non-clinical health and environmental safety studies required by regulations for the purpose of registration.

GOOD LABORATORY PRACTICE “PRINCIPLES”

Key Personnel in GLP

Test Facility Management

o The person(s) who has the authority and formal responsibility for the organisation and functioning of the test facility.

Responsibilitieso Maintenance of a record of the qualifications,

training, experience and job description for each professional and technical individual.

o Appropriate and technically valid SOPs are established and followed.

o Quality Assurance Programme is being performed in accordance with the Principles of GLP.

o Individual with the appropriate qualifications, training, and experience is designated by the management as the Study Director before the study is initiated.

o In the event of a multi-site study, a Principal Investigator is designated.

o Test Facility Management should ensure the documented approval of the study plan by the Study Director.

o Ensure that the SD has made the approved study plan available to the QA personnel.

o An individual is identified as responsible for the management of the archive(s).

o For a multi-site study clear lines of communication should exist between the SD, Principal Investigator(s), the QAP(s) and study personnel.

o Computerised systems should be validated, operated and maintained in accordance with Principles of GLP (Udaka and Horii, 1985)

Study Director

o The individual responsible for the overall conduct of the nonclinical health and environmental safety study.

o The single point of study control.

o Approve the study plan and any amendments by dated signature.

o SD should ensure that the QA personnel have a copy of the study plan and any amendments.

o Study plans (and amendments) and SOPs are available to study personnel.

Responsibilities of SD

o SD should ensure that all raw data generated are fully documented and recorded.

o Computerised systems used in the study should be validated (Taylor, 1984)

o SD should sign and date the final report to indicate acceptance of responsibility for the validity of the data.

o SD should ensure that after completion of the study, the study plan the final report raw data supporting material

are archived.

Principal Investigator

o an individual who, for a multi-site study, acts on behalf of the SD and has defined responsibility for delegated phases of the study.

o The PI should ensure that the delegated phases of the study are conducted in accordance with the Principles of GLP.

Responsibilities of Study Personnel

o Knowledgeable in those parts of the Principles of GLP which are applicable to their involvement in the study.

o Access to the study plan and appropriate SOPs.

o Any deviation from these instructions should be documented and communicated directly to the SD, or the Principal Investigator.

o Responsible for recording raw data promptly and accurately and for the quality of the data.

o Study personnel should exercise health precautions to minimise risk to themselves and to ensure the integrity of the study

(Schechtman, 2007).

Quality Assurance Programme

o "an internal control system designed to ascertain that the study is in compliance" with the Principles of GLP.

o The test facility should have a documented QAP.

o An individual or individuals designated by management, who are familiar with the test procedures (Hughes, 1999)

o should not be involved in the conduct of the study being assured (Becker et al., 2009)

o Maintain copies of all approved study plans and SOPs.

o Verify that the study plan contains the information required for compliance with the Principles of GLP.

o Conduct inspections to determine that all studies are conducted in accordance with the Principles of GLP.

(Hughes, 1999)

Responsibilities of the QA-Personnel

o Inspect the final reports to confirm that,

the methods, procedures and observations are accurately and completely described.

reported results accurately and completely reflect the raw data of the studies.

o Promptly report any inspection results in writing to management and to the SD, or Principal Investigator(s).

o Prepare and sign a statement, which specifies types of inspections and their dates, including the phase(s) of the study inspected.

Facilities

o Suitable size, construction and location to meet the requirements of the study.

o Adequate degree of separation of the different activities to assure the proper conduct of each study

(Garner and Barge, 1989)

Facilities for Handling Test and Reference Itemso Separate areas for receipt and storage of the

test and reference items, and mixing of the test items with a vehicle.

o Storage areas for the test items should be separate from areas containing the test systems.

o Storage areas should be adequate to preserve identity, concentration, purity, and stability.

Archive Facilities

o Archive facilities should be provided for the secure storage and retrieval of study plans, raw data, final reports, samples of test items and specimens.

Archive design and archive conditions should protect contents from untimely deterioration (Udaka and Horii, 1985)

Waste Disposal

o Handling and disposal of wastes should be carried out in such a way as not to jeopardize the integrity of studies.

o Provision for appropriate collection, storage and disposal facilities, and decontamination and transportation procedures.

Apparatus, Material and Reagents

o Apparatus should be suitably located and of appropriate design and adequate capacity.

o Periodically inspected, cleaned, maintained, and calibrated according to SOPs.

o Apparatus and materials used in a study should not interfere adversely with the test systems

(Stevenson, 1992)

o Chemicals, reagents, and solutions should be labelled to indicate identity, expiry date and specific storage instructions.

o Information concerning source, preparation date and stability should be available.

Test SystemsTest Systems

o any biological, chemical or physical system or a combination thereof used in a study.

Physical/ChemicalPhysical/Chemical Location Design Capacity.

o Proper conditions should be established and maintained for the storage, housing, handling and care of biological test systems.

o Newly received animal and plant test systems should be isolated until their health status has been evaluated.

o Acclimatised to the test environment.

Biological

Standard Operating Procedures

o A test facility should have written SOPs approved by test facility management.

o Language interpretable to those who are going to use them (Federick, 2006)

Documented procedures which describe how to perform tests or activities normally not specified in detail in study plans or test guidelines.

o Deviations from SOPs should be documented and acknowledged by the SD or the Principal Investigator.

o Published text books, analytical methods, articles and manuals -supplements to the SOPs.

o Reviewed regularly.

o SOPs should be available for the following categories of activities:

Test and Reference Items Apparatus, Materials and Reagents Record Keeping, Reporting, Storage, and

Retrieval Test System Quality Assurance Procedures.

Content of the Study Plan

o Identification of the study, the test item and reference item.

o Information concerning the sponsor and the test facility.

o Dateso Test Methodso Records

Conduct of the Study

o A unique identification should be given to each study, all items concerning this study should carry this identification (Royal, 1994)

o Specimens from the study should be identified to confirm their origin.

o Conducted in accordance with the study plan.

o Data generated should be recorded directly, promptly, accurately and signed and dated.

o Any change in the raw data should indicate the reason for change and should be dated and signed by the individual making the change.

o Computerised system should always provide for the retention of full audit trails to show all changes to the data without obscuring the original data.

Reporting of Study Results

o The final report should be signed and dated by the SD to indicate acceptance of responsibility for the validity of the data.

o The extent of compliance with the principles of GLP should be indicated.

o Amendments should clearly specify the reason for the corrections or additions and should be signed and dated by the SD

(Ranade, 2007)

Content of the Final Reporto The final report should include, Identification of the Study, the Test Item and

Reference Item. Information concerning the Sponsor and the

Test Facility. Dates QAP statement Description of Test Methods Results Storage (study plan, test and reference items,

specimens, raw data)

Mutual Acceptance of Data

o Testing of chemicals is labour-intensive and expensive, and testing the same chemical in several countries adds to the cost in time, resources and laboratory animals.

o To relieve some of this burden, the OECD Council adopted the concept of MAD in 1981.

o Mutual Acceptance of Data:

“Data generated in a member country in accordance with OECD Test Guidelines and Principles of GLP shall be accepted in other member countries for assessment purposes and other uses relating to the protection of human health and the environment.”

(Turnheim , 2008)

o OECD Council sets out a step-wise procedure for non-OECD countries with a major chemical industry to take part in the work of OECD (Sasaki et al., 2009)

o This leads to full membership in the part of OECD related to the MAD.

o South Africa was the first non-OECD country to have completed this process and to have been invited to join the system as a full member.

o Slovenia and Israel - full members.

o Argentina, Brazil, India (2003) , Malaysia and Singapore are the provisional adherents.

o The provisional adherence procedures have begun for Thailand.

National GLP Compliance Monitoring Authority (NGCMA)

o April, 2002o Department of Science and Technology (DST).o Provisional Member of the OECD for GLP.o Head, National GLP Programme has been

nominated by the Department as an Observer to the OECD’s Working Group on GLP.

o functions as per OECD Norms & Principles and efforts are being made to achieve OECD recognition, so that India acquires full-member status in OECD (Stanley, 2009)

There is still long way to go……………..!

CONCLUSIONCONCLUSION

o The purpose of GLP is to assure the quality and integrity of data submitted in support of the safety of regulated products.

o Protocols, SOPs, adequate facilities, and equipments, identification of test substance, proper animal care, accurate recording of observations and adequate reporting of results are basic necessities for the conduct of high quality valid toxicity study.

o Test results obtained in compliance with GLP are to be mutually accepted by the health authorities and environment authorities of the OECD member states. Therefore, multiple testing can be avoided.