GOOD LABORATORY PRACTICE

Rishabh Nagar

M.Pharm (Pharmaceutical Analysis)

1st year

Department of Pharmaceutical Analysis I.S.F. College of Pharmacy, Moga

INTRODUCTION ON GLP

Definition- Good Laboratory Practice (GLP) is concerned with the organizational process

and the conditions under which laboratory studies are planned, performed, monitored, recorded, and reported.

What are GLPs? In the 1970s, FDA inspections of nonclinical laboratories revealed that some

studies submitted in support of the safety of regulated products had not been conducted in accordance with acceptable practice, and that accordingly data from such studies was not always of the quality and integrity to assure product safety.

The FFDCA and Public Health Service Act require that sponsors of FDA-regulated products submit evidence of their product’s safety in research and/or marketing applications.

These products include food and color additives, animal drugs, human drugs and biological products, human medical devices , diagnostic products, and electronic products.

HISTORY:- GLP is a formal regulation that was created by the FDA (United states food

and drug administration) in 1978. Although GLP originated in the United States , it had a world wide impact. Non-US companies that wanted to do business with the United states or

register their pharmacies in the United States had to comply with the United States GLP regulations.

They eventually started making GLP regulations in their home countries. In 1981 an organization named OECD (organization for economic co-

operation and development ) produced GLP principles that are international standard.

WHY WAS GLP CREATED?In the early 70’s FDA became aware of

cases of poor laboratory practice all over the United States.

FDA decided to do an in-depth

investigation on 40 toxicology labs.

They discovered a lot fraudulent activities and a lot of poor lab practices.

Examples of some of these poor lab practices found were

1. Equipment not been calibrated to standard form , therefore giving wrong measurements.

2. Incorrect/inaccurate accounts of the actual lab study

3. Inadequate test systems

KEY DATES

1970 1976 FDA GLP proposed

1978 FDA GLP regulations published1980 1982 OECD GLP published (30 countries incl. U.S.), UK

GLP published, Japanese GLP published1983 EPA GLP regulations published1986 FDA GLP revised, European Union GLP Directives1989 EPA GLP revised

1990 1998 OECD GLPs revised, Canadian PMRA adopted GLPs

2000 2002 OECD consensus document 2007 EPA may consolidate two parts of EPA GLPs

NATIONAL ARCHIVES AND RECORD ADMINISTRATION:-

Code of Federal Regulations (CFR)

Title 40 Protection of Environment (laws and regulations of U.S. EPA)

Part 160: Good Laboratory Practice Standards, Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), Subparts A-J

Part 792: Good Laboratory Practice Standards, Toxic Substances Control Act (TSCA), Subparts A-J

Note: FIFRA regulates pesticides and TSCA regulates toxic substances

TestFacility

Sponsor Approve?

Submits Data Regulatory

Agency (EPA, FDA)

Yes! Permission to

Market Regulated Product

No!

Permission to Market Regulated Product Denied

Internal audits and inspections (conducted by Quality Assurance Unit)

External audits and inspections of sponsor and test facility (conducted by regulatory agency)

The Regulatory Processof GLPs

SCOPE OF GLP :- These principles of Good Laboratory Practice should be applied to testing

of chemicals to obtain data on their properties and/or their safety with respect to human health or the environment.

These principles of Good Laboratory Practice should be applied to testing

of chemicals to obtain data on their properties and/or their safety with respect to human health or the environment.

GLP is a requirement in regulatory non-clinical safety testing of the following test items-

Pharmaceutical products Pesticide products Cosmetic products Veterinary drugs Food additives Industrial chemicals

PURPOSE OF THE GLP :- Improve data quality Obtain reliable and reproducible data Obtain comparable quality between countries Achieve international confidence in study data. Avoid repetition of studies. Optimize animal condition. Shorten the registration time of the drug.

IMPORTANCE OF GLP FDA uses these data to answer questions regarding:- The toxicity profile of the article. The observed no adverse effect dose level in the test system. The risks associated with clinical studies involving humans or animals. The potential teratogenic, carcinogenic, or other adverse effects of the

article. The level of use that can be approved.

TYPE OF TESTS:-

Physico-chemical properties Toxicological studies designed to evaluate human health effects Ecotoxicological studies designed to evaluate environmental effects Ecological studies designed to evaluate environmental chemical fate

(transport, biodegradation, and bioaccumulation)

GLP REGULATIONS: RULES AND TOOLS

Chemical and sample inventory, track expiration dates, labeling

TEST, CONTROL, AND REFERENCE SUBSTANCES

Timely reporting, storage of raw data and reports

RECORDS AND REPORTS

Standard operating proceduresFACILITY OPERATION

Calibration, logbooks of use, repair, and maintenance; check freezers

EQUIPMENT

Maintain adequate space/separation of chemicals from office areas

FACILITIES

Training records, CVs, GLP trainingORGANIZATION AND PERSONNEL

Documentation (Tools)GLP Regulations (Rules)

ELEMENTS OF GLP

1. General provision (58.1)2. Personnel (58.29)3. Building and facilities(58.41)4. Documentation(58.81)5. Calibration(58.63)6. Validation of analytical methods7. Change control8. Laboratory reagents and solutions(58.83)9. Control of animal house(58.90)10. Safety11. Training 12. Quality audit13. Management review

GENERAL PROVISION:- A drug control laboratory is maintained by the drug regulatory

authority for carrying out the tests & assays required to establish that a drug conforms to the quality specifications claimed for it.

The contribution of a drug control laboratory to a national drug control system was described in the twenty-seventh report of WHO expert committee on specification for pharmaceutical preparations.

A control laboratory can provide effective support for a drug regulatory agency and its inspection services.

It describes accurately properties of the samples to permit the correct quality of each drug, and to serve as an adequate basis for any subsequent administrative and legal action.

Correct assessment of quality of a drug sample is dependent on:-

The submission of a representative sample to the laboratory, together with a precise indication of why the test is requested.

A correctly planed and meticulously executed analysis; and A competent evelutoion of the results to determine whether the

sample complies with the specification.

PERSONNEL:-

Medical check up Health & hygiene Training of personnel Job description

BUILDING & FACILITIES

Maintain building & Facilities

Clean Epoxy Flooring and wall coving - effective cleaning and no Dirt

accumulation

ARRANGE TO HAVE SUFFICIENT SPACE FOR STORAGE

LAY OUT OF LABORATORY:-

DOCUMENTATION:- The availability of a complete set of SOP necessary to govern all the

pertinent activities and procedures in the test facility is an absolute prerequisite.

They define how to carry out protocol specificities. Some of the key SOPs which need to be addressed include:- The samples handling and accountability. Receipt, identification, storage, method of sampling of test articles. Record keeping, reporting, storage and retrieval of data. Operating of technical audit personnel in conducting and reporting

audits , inspection, reports, reviews. Routine inspection of cleaning maintenance, testing, calibration of

equipment. Calibration management. Validation of analytical methods.

Change control procedure. Animal room preparation & animal care. Storage, maintenance and traceability of microbial cultures. Storage, use of reference standards and reagents. Laboratory waste handling. Record data using permanent ink (never pencil) Date and sign every entry (who is responsible?) Keep records in “real time” (no catching up later) No rewrites, need original entries (reduces transcription errors)

CALIBRATION :-

Calibration: equipment is adjusted based on comparison to certified or known reference materials (balance adjusted after comparison to certified weights by trained professional)

Verification (Testing): external check of equipment accuracy (check balance accuracy against weights at laboratory- no adjustment

VALIDATION OF ANALYTICAL METHODS:-o All analytical methods, particularly none –standard & in-house test method

must be validated by a procedure given below.o All analytical equipment must be appropriately qualified before method

validation.o The validation methodology must clearly documented & should include:- Selectivity & specificity. Range. Linearity. Robustness Precision. Limit of detection. Limit of quantification.

A record must be maintained of any modification of the validated method and should include reason for modification

and appropriate data to verify that results are as accurate and reliable as the established method.

CHANGE CONTROL

All changes in equipment, test environment, test method, services, system or location that may affect reproducibility, accuracy or standards must be formally requested, documented and accepted.

LABORATORY REAGENTS AND SOLUTIONS :-

о Their must be written procedures in place for the handling of

reagents and preparation of standards solutions.о All reagents and solutions in the laboratory areas shall be labeled to

indicate identity,concentration, storage requirements, expiration date.о Deteriorated or outdate reagents and solutions shall not be used.

Good laboratory technique has always included proper labeling of

reagents & solutions .о SOP should be maintained for the storage at ambient room

temperature unless otherwise indicated on the label. о Official FDA enforcement policy requires adherence to GLP

labeling requirements for all reagents and solutions in a laboratory in

which GLP regulated work is conducted even if some of those

reagents and solutions are used for work that is not GLP regulated.

General Expiration Guidelines:

• Dry reagents: 5 years (unless reevaluated)

• Solvents: 1 year from date opened or 2 years from date received

• Solutions: Use the earliest date of components in the solution or no longer than 6 months

CONTROL ON ANIMAL HOUSE :-

o SOPs for housing, feeding, care, handling.o Newly-received animals; isolated and health status determined

animals free of disease before and during study.o If diseased during study, treatment should not interfere with study

and be documented.o Warm-blooded animals if removed from home cage; identified (ID

on outside of housing unit)o Different species in separate rooms when necessary. Same

species/different studies; ideally separate roomso Cages, racks; cleaned/sanitized(appropriate interval.)

o Feed and water analyzed periodically for contaminants that may affect study should be documented.

o Bedding should not interfere with study.o Pest control materials should not interfere with study.

SAFETY:-

o People who work in scientific laboratories are exposed to many kind of hazards so safety of people should be considered.

o The design and construction is the first instance of building safety features in the laboratory.

o Laboratory must be equipped with:- Adequate fire extinguishers. Personnel protecting equipment. Eye wash fountains & first aid kits.o The design should facilitate the change of street clothes and

footwear by the specific laboratory personnel.o No food, beverage or cosmetic product should be allowed in the

laboratory or chemical storage area at any time.

TRAINING :- Test facility management must provide training for all personnel

whose duties involve the conducting of tests and analysis. Training appropriate to the duties assigned to them. A particular SOP should be documented for a training program. The records of their educational and professional qualification,

training undergone, skills and experience shall also be maintained.

QUALITY AUDIT:- The QA program or self audit should be carried out by an individual

or by individuals who are designated by & directly responsible to the facility manager and who are thoroughly familiar with the test procedures

These individual must not be involved in the conduct of the study/ test being assured.

The responsibilities of these QA / audit personnel include:-o Maintain a copy of all approved test method / study plan/ SOP use

in test facilities.o Verify that test methods/study plans contain the information

required for compliance with the principles of GLP.

Conduct audits/ inspections to assure that tests are conducted in accordance with these principles of GLP.

Inspections can be of three types :-

A. Study / test based inspections

B. Facility based inspection

C. Process based inspection Document and retain records of all inspections Inspect the final repots to confirm accurately and completely

described method procedures.

MANAGEMENT REVIEW:-

Management of a test facility as the ultimate responsibility for ensuring that the facility as a whole operate in compliance with the GLP principles.

Quality audit and Quality assurance program which is independent of the actual conduct of test/ study and is designed to assure the test facility management of compliance with these principles of GLP.

REFERENCES:- http://www.sjsu.edu/faculty/chem55/55glpout.htm http://www.labcompliance.com/tutorial/glp/defaul UGA Office of the Vice President for Research Wikipedia Code of Federal Regulations (CFR)

• EPA GLP Regulations

• FDA GLP Regulations

• USDA- Pesticide Data Program (PDP) Standard Operating Procedures

• Weinberg Sandy, “Good laboratory practice regulations”, third edition, volume 124, Marcel Dekker publications, New york.