GLP (Good Laboratory Practice) | How To Implement

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GLP regulates pharmaceutical development qualitatively and quantitatively. Be it is purchasing materials or process control or intermediate stages or final Active pharmaceuticals GLP plays a vital role. That is why I decided to share my skill-based knowledge on this topic. In this article, you will learn GLP, 21CFR part 58, 21CFR part 11, elements of GLP, QAU and the role of GLP in managing sop, GDP (good documentation practice) stp, protocol, report, validation, reference standards, equipments, calibration and solutions.

GLP (Good Laboratory Practice)

GLP (Good Laboratory Practice) is a quality control system covering the organizational process and the conditions under which non-clinical health and environmental studies are planned, performed, monitored, recorded and reported.

The Aim of the GLP

• To establish safety culture during pharmaceutical development stage
• To promote pharmaceutical development with high quality test data
• Generate reliable and reproducible data

6 Key Elements of GLP

A laboratory which intends to perform GLP compliant studies should be organized. The following are 6 key elements of GLP organization:

1. Study Director or Head of Department: He or she is overall responsible to control (conduct, interpret, analyze and report the studies result) the studies. He or she should not be overloaded and free to monitor the studies.
2. QA or Quality assurance unit: QA personnel are responsible to audit the Laboratory studies
3. Personnel: They are well educated and skilled to conduct laboratory studies
4. SOP or Standard operating procedure: These are written and approved documents to conduct all laboratory activities
5. STP or standard testing procedure: These are written and approved documents to conduct analysis. It contains details of analytical method of a pharmaceutical.
6. Reference standards: Only the standard characterize using appropriate analytical techniques (like NMR, mass, and FTIR) and calculated potency using an approved chromatographic method should be used for laboratory studies. Standard bottle label should include storage condition, potency, date of opening the bottle, quantity and expiration date.
7. Reagents and solutions: All solid chemicals, liquid chemicals, reagents and solutions must be labelled. Label must contain concertation, date of preparation/ manufacturing, date of opening, quantity and expiry date.
   • Date of preparation
   • Concentration/standard factor
   • Shelf life
   • Date of expiry
   • Prepared by
8. Raw data: Paper notebook should be used to write all laboratory actvities. Data should be reviewed and signed off by laboratory incharge. Nowadays electronic notebooks are also used to write down the raw data.
9. Storage and achieving: There should be a separate room to store all the documents like SOPs, STPs, protocols, reports and raw data. Storage should be done using SOP.
10. Analytical Techniques/Equipments: All equipment used laboratory study and generating data must be in working condition and have history files and SOPs (operational and calibrational). Calibration should be done as per calibration plan or after any break down (as mentioned in the SOP)
11. Protocol and GLP: Activities like validation, tech transfer should be conducted as per defined and pre-approved SOP

GLP and Validation

Validation is one of the most important key requirements of GLP and it includes:

• Equipment hardware validation
• CSV (Computer System Validation)
• System validation
• Analytical method validation and
• Data validation

GLP and Verification/Mini-validation

Method Verification/Mini-validation is performed during pharmaceutical developments to see the authenticity of the developed method under GLP condition. It is performed prior to complete validation or as per regulatory requirement.

DQ, IQ, OQ, PQ, and GLP

• DQ (design qualification): DQ must meet the user specification. For example, if the user requires HPLC with binary gradient system, an isocratic HPLC system will not solve the purpose. The necessary and sufficient condition is that there will be no validation if system does not satisfy the user’s requirement.
• IQ (Installation qualification): IQ verifies that the instrument has arrived as purchases and that it has been properly installed
• OQ (Operational qualification): OQ verifies that the instrument functions and performs in the user laboratory as defined in the DQ
• PQ (Performance qualification): PQ includes preventive maintenance an regula test such as system suitability test (SST). For computer system it includes regular data back up, virus checks and change control procedures.

Role of GLP in Stability Studies

GLP plays a vital role in stability studies such as in deciding stability condition, such as in designing the stability protocol and report. Stability studies are performed to evaluate how the quality of a pharmaceutical changes over time under the influence of environmental factors like temperature, humidity, and light.

GLP helps in the following ways stability studies:

1. Quality and Reliability of Data: GLP guidelines ensure that the methods, equipment, and processes used during stability testing are consistent and accurate. This helps ensure that the data generated is reliable and reproducible.
2. Documentation and Record-Keeping: GLP mandates thorough documentation of all processes, protocols, and results. Proper records are crucial in stability studies to track changes over time, verify conditions, and confirm compliance with regulatory requirements.
3. Standardization of Procedures: Stability studies involve various testing procedures (e.g., accelerated stability testing, long-term stability testing). GLP ensures that these procedures are standardized, making sure tests are carried out in the same way each time, reducing variability in the results.
4. Regulatory Compliance: For pharmaceutical products or chemicals, regulatory bodies (such as the FDA, EMA, or ICH) require stability data to be generated according to GLP standards. This ensures the data can be submitted for DMF filing and meet safety and efficacy requirements.
5. Traceability and Accountability: GLP guidelines require traceability of materials and reagents used in the study, personnel involved, and equipment calibration. This ensures accountability, helping to identify the source of any errors or issues during testing.
6. Risk Management: Stability testing under GLP involves thorough planning and protocol design

21CFR Part 11 and GLP

The 21CFR part 11 (electronic signature and records) deals with data security, integrity, traceability of the Analytical research department, The following are the primary requirements of an Analytical Laboratory as per 21CFR part 11:

• Authorised and traceable access to systems applications
• Use of the Electronic audit trail
• Secure retention of electronic records to instantly reconstruct the analysis
• Implementation of data security, data integrity and confidentiality through limited authorized system access
• Use of secure electronic signatures for closed and open systems
• Mechanism to delete or change records

Note:

• When the study results are submitted to the FDA, archived records must be retained at least for 5 years.
• When the study results are not submitted to the FDA, archived records should be retained at least for 2 years.

7 Step Data Correction Procedure or what is data correction procedure as per GLP?

In the context of Good Laboratory Practice (GLP), data correction refers to the process of rectifying errors or discrepancies in raw data while ensuring the integrity, traceability, and authenticity of the data is maintained. The GLP guidelines establish stringent procedures to manage data correction and ensure the reliability of scientific results. The following steps must be followed while correcting the data:

1. Identification of Error
   • Errors or inconsistencies in raw data (e.g., measurement errors, transcription mistakes, or missing data) must be identified.
2. Documentation of the Error
   • Any error detected must be documented clearly, including the nature of the error, how it was found, and any possible causes.
3. Correcting the Data
   • If an error is found in a physical or electronic data record (e.g., a lab notebook or a computer system), the correction should be made by crossing out the incorrect data with a single line and inserting the correct data next to it.
   • For electronic records, the correction should be made in such a way that the original, incorrect data is still traceable. This could involve using comments or annotations, and any changes should be logged in the system with the time and date.
4. Initialing and Dating
   • The person making the correction must initial and date the correction to indicate responsibility and the timing of the change. This helps maintain traceability.
5. No Overwriting of Data
   • Raw data must not be overwritten or erased entirely. For example, if data is recorded on paper, strikethroughs or corrections should be clear, and for electronic systems, proper audit trails should be maintained.
6. Approval of Corrections
   • In many cases, corrections must be reviewed and approved by a supervisor or authorized person. This ensures that the correction is appropriate and does not alter the scientific integrity of the results.
7. Record Keeping and Audit Trails
   • The original data, along with any corrected data, must be retained and available for review. If using electronic systems, a proper audit trail should be maintained that records each change made, by whom, and when.

The idea is to ensure that any correction made to data does not compromise the quality, accuracy, and traceability of the original observations, and to maintain the credibility and integrity of the data as per GLP standards.

Case study: How to make typo correction

The following approach should be adopted while doing the correction

What are differences between GLP and GMP?

Typical Examples of GLP

The following are some examples of GLP:

• Always wear PPE (personal protective equipment) during the laboratory experiment
• Reas MSDS prior to start the experiment
• Work according to standard operation procedure
• Participate in the refresher training and safety exercises
• Maintain log book for each laboratory activities
• Keep the instrument clean
• Calibrate the instrument prior to schedule date
• Implement internal and external audit system

OOS, OOT, CAPA and GLP

OOS (Out of specification), OOT (Out of trend) and CAPA (corrective and preventive action) are governed by GMP guidelines

Advantages of GLP

The following are the advantages of the GLP:

• Safety compliance culture
• Better and safe workplace
• Confidence in result
• Auditable workplace

GLP and Document Archiving Policy

Good Laboratory Practice (GLP) guidelines outline a clear set of requirements for document archiving to ensure that data generated during studies is preserved, accessible, and can be audited for regulatory purposes. The key points regarding document archiving under GLP include:

1. Retention Period: GLP requires that raw data, study documentation, and related records be archived for a minimum period of five years following the final report submission, unless otherwise specified by applicable regulations or the nature of the study.
2. Data Integrity: All documents must be kept in a secure and organized manner, ensuring they cannot be altered or lost. Proper control measures should be in place to protect against unauthorized access or modifications.
3. Accessibility: Archived records should be readily accessible for inspection by regulatory authorities or for internal audits. Systems and procedures should allow for quick retrieval if needed.
4. Conditions of Storage: Archives must be stored in a controlled environment that protects them from damage due to environmental factors such as moisture, temperature, or fire. This could involve physical or electronic storage systems.
5. Responsibility for Archiving: The study director is typically responsible for ensuring that all relevant documents are archived and that they comply with GLP standards.
6. Electronic Records: If electronic systems are used for record-keeping, they must comply with 21 CFR Part 11 (for U.S. regulatory requirements), ensuring data security, integrity, and audit trails.
7. Destruction of Records: Records should only be destroyed after the required retention period has elapsed, and this process should be properly documented.

Each organization must ensure that their document archiving practices comply with the GLP regulations relevant to their jurisdiction and type of study.

Advancements in Technology and GLP

Automation and digitalization have revolutionized laboratory processes, enhancing data integrity, and research efficiency. These advancements have enabled laboratories to streamline workflows, reduce human errors, and improve data management.

Laboratories now utilize sophisticated laboratory information management systems (LIMS) and electronic lab notebooks (ELNs) to capture and analyze data more efficiently. These digital tools allow for seamless integration of experimental data, provide enhanced traceability, and enable better collaboration among researchers

Related topic: Analytical Method Development and Validation in Pharma

Conclusion

I hope this article has helped you understand GLP or Good Laboratory practices and its importance in pharmaceutical companies. Now you have the knowledge to implement the GLP culture in the department.

You may also want to check out other articles on my blog, such as:

• How to make strategy for QC USFDA audit?
• How to Prevent Data Integrity Violation in Pharma

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FAQs/Interview questions on GLP

References

• A good laboratory practice and current good manufacturing practice, Ludwig Huber, Agilent
• https://safetyculture.com/topics/good-laboratory-practice-glp/

Abbreviations

• GMP: Good manufacturing practice
• GLP: Good laboratory practice
• CFR: Code of federal regulation
• AMV: Analytical method validation
• SOP: Standard operating procedure