Good Laboratory Practice (GLP) regulations became part of the regulatory landscape in
the latter part of the 1970s in response to malpractice in research and development (R&D)
activities by pharmaceutical companies and contract facilities used by them.
The malpractice included cases of fraud, but by far the most important aspects were the
lack of proper management and organization of studies performed to generate data for
regulatory dossiers.
The US Food and Drug Administration (FDA) mounted a series of
investigations in toxicology laboratories throughout the USA. The results of these investi-
gations revealed a situation that could only be dealt with by imposing binding regulations.
These regulations are the GLP regulations. GLP regulations were first instituted by US
FDA, then by US Environmental Protection Agency (EPA); many other countries have
since followed suit.
THE OECD GLP PRINCIPLES
GLP started when the FDA issued mandatory GLP requirements on 20 June 1979. The
FDA subsequently revised these regulations a number of times but it has never altered its
scope; regulations still apply to non-clinical safety studies applied to drugs.
Preliminary pharmacological studies and pharmacokinetic studies not designed to test safety are still exempt from GLP requirements. A little later, the OECD introduced the OECD Principles for GLP (GLP Principles) concerning the safety testing of any chemical substance. This GLP text is binding on all 30 OECD member states. This is why these GLP Principles have
been adopted as the basic rules for the training programme devised for the WHO/TDR.
The OECD recognizes that not all parts of the GLP Principles are easy to interpret. This
is why the OECD has published a series of advisory documents on various aspects of the
GLP Principles. In all, there are 15 OECD documents concerning GLP (including the GLP
Principles). Many of these have been derived from discussions between regulators and
members of industry during consensus workshops. The contents of the documents represent the current thinking of the OECD. Any member state can request that a particular
subject be discussed during a consensus meeting. It is up to the OECD to decide whether
the subject merits a full three-day consensus type meeting.
The OECD has established a GLP Group made up of senior members of the respective
member states’ GLP monitoring authorities. This group oversees the GLP activities of the
OECD. The activities include the organization of training courses for GLP inspectors from
all over the world and the organization of joint inspections. Together, these help to har-
monize the approach of the various member states to GLP inspections.
In 1981, the Organization for Economic Cooperation and Development (OECD) also
published GLP Principles, and these now dominate the international arena. To date 30
countries (the member states of the OECD) have signed an agreement binding them to
OECD GLP Principles. Other non-OECD member states have also adopted the OECD
GLP Principles.
The intent of GLP is to regulate the practices of scientists working on the safety testing
of prospective drugs (and other chemical or biochemical entities). With the obvious
potential impact on patients taking medicines and on people recruited for clinical trials,
the safety of drugs is a key issue and GLP is seen as a means of ensuring that scientists do
not invent or manipulate safety data, and as a means of ensuring that studies are properly
managed and conducted, thereby considerably increasing the chances of producing valid
experimental data. GLP compliance is a guarantee that safety data are being honestly
reported to the registration authorities. The results of these studies form the basis for the
decision to proceed with clinical trials, prior to allowing a new drug onto the market. GLP
was imposed on industry by regulatory authorities in the same manner as Good Manufacturing Practice (GMP) had been before, and Good Clinical Practice (GCP) would be later.
Good Laboratory Practices (GLP) was first introduced in New Zealand and Denmark in 1972, and later in the US in 1978. It was followed a few years later by the Organization for Economic Co-operation and Development (OECD) Principles of GLP in 1992 & the OECD has since helped promote GLP to many countries.
GLP is not only limited to chemicals but also it applies to medical devices, food additives, food packaging, colour additives and other non-pharmaceutical products or ingredients as well.
Good Laboratory Practice contains a set of principles that provides a framework within which laboratory studies (Activities) are planned, performed, monitored, recorded, reported and archived. GLP help assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be confidence upon when marking risk/safety assessment.
Why GLP is Important in Pharmaceuticals :
Good Laboratory Practice contains different principles which are designed to ensure and promote consistency, quality, safety, reliability and integrity of chemicals during non-clinical and laboratory testing.
Basic Rules of GLP :
- Make sure to have the correct written instructions before starting a task.
- Do not carry out task for which you have not been trained.
- Keep records of information, results and actions taken. Make clear accurate records of what was done.
- Check that the instrument/ equipment/material used are clean, calibrated and correct ones as per procedure.
- Always notify if labels are seen either detached or appear to incorrect or are in wrong place.
- Never remove a label which has been incorrectly applied and never stick a new label over an old one of the same type. If label is incorrectly affixed strike it off, sign and paste new correct label adjacent to it
- Clean the glassware drying oven, refrigerator, walk in chamber incubators, water bath of the instruments like dissolution tester, disintegration testers etc, used in the quality control laboratory as per the procedure.
- Clean the work benches after completion of work or at the end of the day whichever is earlier and keep the respective specification, General test procedure (GTP), Standard test Procedure (SOP’s) etc used back to the designated place.
- While closing the Quality Control Laboratory, ensure that all water taps, instruments (which are not running), equipments, computers are put ‘OFF’. Put off the lights, AC’s and closes the department.
Premises and Utilities :
- Maintain the laboratory and its premises clean.
- Keep work benches of laboratories clean and tidy all the time.
- Keep the samples, standards, laboratory reagent, apparatus, accessories and records at adequate and suitable storage space.
- For analytical preparation wherever water is to be used, use purified water for chromatographic analysis like HPLC, GC, etc. use HPLC grade water or water generated by Milli-Q system.
- The utilities like compressed air, vaccum required for the functioning of laboratory should have identification mark.
- Maintain temperature and humidity record as per respective procedure wherever applicable.
- Follow the procedure in case access control system is to be followed where restricted entry is necessary 8. In case of hazardous and poisonous materials, keep it at adequate storage area/facility with lock and key to avoid misuse. Also keep reserve sample, stability sample, laboratory standards in lock and key Use eye washer, water shower, first aid kit etc. in case of emergency which may arise during operation & Always identify the location of emergency exit in the laboratory for exit during emergency
Personnel :
- All personnel prior to employment should be periodically re-examined for medical fitness. The Quality Control Manager should ensure that the personnel are medically fit to carry out the job.
- Personnel suffering from an infectious disease or having open lesion on the exposed surface of the body should not engage in activities that could results in compromising the quality of analysis.
- All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.
- The job responsibility should be assigned according to competency of the person and it should be timely revised for addition or deletion of responsibilities assigned previously.
- Smoking, eating, drinking,chilling or keeping plants, food,drinks and personnel medicine should not be permitted in laboratories area, where they might adversely influence the product quality.
- Personnel should wear clean clothing (company uniform)suitable for activity with which they are involved and this clothing should be changed when appropriate. Personnel should strictly follow entry/exit and gowning procedure.
- While handling hazardous chemicals and while performing sterility, microbiological analysis, procedure of change of clothing and use of personnel protective equipment’s and safety appliances should be strictly followed.
- Never handle any chemicals, raw materials intermediate & finished, unpacked product with bare hands. Always use the appropriate hand gloves while handling the same.
Training :
- Training should be regularly conducted by qualified individuals and should cover, at a minimum, the particular operation that the employee performs. Training should be given on both the theory and practice of the work being undertaken in a particular area, as well as relevant ‘on-job’ training.
- Records of training must be maintained. Training should be periodically accessed. All staff, including new staff and existing staff should be given basic training on Good Laboratory Practices during induction and at regular intervals subsequently. This training programme should be periodically updated.
Instruments / Equipments / Accessories :
Stability Studies :
Stability studies should be carried out to obtain evidence on how the quality of a drug substance or drug product varies with time under the influence of factors such as temperature, humidity and light and enables establishment of recommended storage conditions, retest periods or shelf life for drug substances or drug products.
A schedule should be designed to monitor the stability of each product .
Out ofspecification or significant a typical trends should be investigated. Product failures should be promptly reported to technical head, regulatory affairs, R and D, quality assurance and customer, (if applicable), for necessary action. The possible impact on the batches distributed in the market should be considered.
Asummary of data generated should be written and maintained. This summary should be subjected to periodic review.
Chemicals , Reagents, Glassware and Analytical Standards :
All reagents and solutions in the laboratory shall be properly identified with a label. Validity should be provided as appropriate for analytical reagents or standard solutions prepared and should be indicated on label together with specific storage conditions.
Check the validity period of chemicals before use & standards and solutions should be labelled .All the solutions, solvents dispensed and solvent waste collected in vessel / beaker should be covered entirely with appropriate cover.
The glassware should be examined before use for cleanliness and damage; do not use cracked, chipped or any other defective glassware.
Documentation :
Specifications, instructions, procedures and records must be free from errors and available in writing.
Documents should be approved, sign and dated by appropriate and authorized persons.
Records should be made or completed at the time each action is taken and in such a way that all significant activities are traceable.
Equipment
SOP s must be present for each instrument
They must be stored under recommended environmental conditions & calibrated regularly
Light & electrical systems must be as per regulations & not overloaded
Glassware must be calibrated & certified for use.
Chemicals & reagents
Storage of chemicals must be done as per the MSDS sheet All chemicals must be appropriately labelled and stored with their MSDS sheet
Any transfer must occur with a proper audit trail
Any prepared solution must be labelled and dated with an expiry date,Mouth pipetting is unacceptable; use a rubber suction pump instead .
Organisation & personnel
Every individual in the laboratory must have the necessary qualification and training to participate Sufficient number of personnel must be employed Every individual must be given personal protective equipment (PPE)
A well-defined organogram of the laboratory must be drawn up and assigned based on the roles required .
Documentation
Every single procedure, event, and entry/ exit must be recorded SOPs for usage, maintenance, and calibration must be provided for each equipment ,All samples/ reagents must be labelled and stored as per guidelines
Examples: Sampling, Validation, Testing, Data recording, Operation, etc.
Quality Control
For samples: Documentation of receipt, usage and storage ,Sampling procedure and testing methodologies used must be recorded.
Lab Safety
Personnel must be required to undertake required immunisations and protective measures before beginning their experiments
Facilities & accessories must be present for first aid, drug testing, accidents such as water leakage or fires .
Auditing Procedure
A dedicated committee must be instituted to maintain the quality standards of the laboratory
It must be done in accordance with GLP requirements.