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Management Process of Good Laborarory Practices

INTRODUCTION

HISTORY OF GLP

NEED OF GLP

MANAGEMENT PROCESS OF GLP

CONCLUSION

MANAGEMENT PROCESS OF GLP

1.Personnel – There are 2 chapters of regulations for personnels. For GLP studies with right quality, things listed below are considered important-

Sufficient number of employees
Personnels should be qualified.

Qualification can be relevant educational background, experience or training, but it must be documented. Apart from this, job profiles, tasks and responsibilities must also be documented.

2. Facilities - This includes a number of responsibilities listed below-

Appointment of a study director
Monitoring the entire study process. If there happens to be any discrepancy in the process, then the study director is replaced.
Ensuring that quality assurance unit is available
Handling tests and control articles
Availability of sufficient qualified personnels for study.
Animal care facility requirements
Storage facilities

The three main requirements for facilities includes limited access to the building rooms, adequate size and construction.

3. Study Director- The study director is responsible for-

Technical conduct of safety studies.
Interpretation of the results
Analysis of the results
Documentation of the results
Reporting of the results.

4. Quality Assurance Unit (QAU)- It serves to control internal functions. These include-

Ensures that facilities, devices, personnels, practice, protocol, records, SOPs, reports and archives are in accordance to the GLP regulations.
Immediate reporting of problems along with actions recommended and taken, and scheduled date for inspection in a written format.
It is mandatory that the responsibilities applicable to QAU and records maintained by QAU with the indexing of these records, are maintained in writing.
Master schedule sheet containing test system, nature and date of the study, identity of sponsor and name of the study director are to be indexed by test articles.
Maintaining protocol of the study for which QAU is responsible.
Inspection of studies at regular intervals to assure integrity of the study and maintain properly signed records of each inspection.
Ensuring that the derivatives from protocols and SOPs were made with proper authorization and documentation.
Final review of the report to ensure that the results accurately reflect the raw data.
Prepare and sign a statement to be included in the final study report specifying dates of audits and reports to the management and study director.

5. Equipment- GLP regulation also specifies requirements for equipment. These are pertaining to

Design- Equipments used for generation, measurements and assessments of study data shall be of appropriate design and capacity. They shall be suitably located for operation, inspection and maintenance. Validation of equipments must be done to make sure that consistent intended functions are performed.
Maintenance- Cleaning and maintenance of equipments is very critical. They must be adequately tested, calibrated and standardized. The entire process is called qualification for equipments. Time interval for calibration, re-validation and testing of of equipments depends on the equipment itself, laboratory experience and extent of use.
Records and other documents – Written records shall be maintained for qualification of equipments and validation operations including date of operation, and specify is SOP s were followed for conducting maintenance operation. These equipment records can be maintained in the form of a log book.

6. SOPs – Standard Operating Procedures (SOPs) specifies the manner in which a protocol-specified activities are carried out. SOPs are written in the given series of steps-

Regular monitoring of the maintenance, testing, calibration and standardization of equipments.
To deal with equipment failure
Analytical operations
Data handling, storage and retrieval
Safety precautions
Recording, storing and retrieval of data.
Data handling and use of computerized systems.

SOPs are preferably written and reviewed by instrument operators. The working of SOPs ensure that information is accurate and document is liable for routine use. FDA's warning letter contains 3 devations for SOPs including unavailability, inadequacy and non-consideration of SOPs. To begin with, a SOP is designed on writing SOPs, which defines who is responsible for initiating, authorizing and approving SOPs.

7. Reagents – The quality, purchasing and testing of reagents and solutions used for GLP studies shall be handled by QAU.

All reagents shall be labeled to specify titer, concentration, storage requirements, and expiry date.
Reagents for GLP and non-GLP regulated studies must be labeled separately.
Date opened must be included which can be critical for some chemicals.
Reagents or solutions without any information about storage temperature do not require cool storage conditions.
Expiration date can be mentioned based on literature or laboratory experience.

8. Test and Control Articles – Control articles are also referred to as reference substances by OECD. They are commonly used to calibrate the instruments. Test results depends on the accuracy of reference article. The requirements for control articles include-

Determination and documentation of the features like identity, strength, purity and other characteristics for each batch.
Method of synthesis, fabrication and derivation of test and control article should be documented.
Copies of this document must be available for FDA inspection.
Stability of test and control articles must be determined.
Storage container for test and control articles must be labeled
Certified appropriate standards can be purchased from appropriate suppliers.

9. Retention and Retrieval of Records- GLP regulation specifies how records are stored and retrieved.

Achieved data- This includes all the documents from raw data to final results along with protocols from meetings and decisions taken. GLP requires an archivist. Any document taken out of the archive must be documented and signed by the person who requested it.

Retention period- In US material supporting FDA submission should be retained for 2 years after FDA approval, and 5 years after FDA submission. According to GLP regulation original copy of the record can be retained. This exact copy can be a copy of a instable thermo paper or plain paper or paper records scanned into TIF or PDF files.

Raw Data- Raw data is defined as any laboratory worksheet, memorandum, or exact copies thereof that are the result of original observation of the study. Raw data may include hand-written notes, photographs, print-outs, magnetic media, and recorded data from automated instruments.

Electronic records – There's no requirement of electronic records as long as the print-out includes every information that is necessary to reconstruct the study.

10. Inspection – FDA is responsible for inspection of GLP studies before a drug or device or any other product is marketed in US. There are 2 types of inspection programs.

Routine Inspection- This should be conducted every second year to ensure that laboratory's compliances are in accordance with the GLP regulations.
For-cause Inspection- They are conducted less frequently, only about 20% of all GLP inspections. FDA conducts such inspections only when it suspects non-compliance while NDA applications.

If the laboratory refuses to accept FDA inspections, then FDA will not accept studies in support of new drug application.

11. Enforcement- If the inspection team finds deviation, they mention these deviation in a particular form. These deviations are discussed in exit meeting. The lead inspector then prepares a establishment inspection report and depending on the deviations, warning letter is issued. This letter is issued to the company's management and corrective action plans are implemented by the company within 14 days.