Laboratory Compliance

Laboratory compliance or lab compliance refers to procedures, policy and general approach required in a laboratory to guarantee the analytical results generated are evocative, convincing and appropriate for the decisions which will be made from the data.

Cost of non-compliance
Following processes and operations needs to be put on highest vigil to find out early any occurrences of non compliance which can lead to failure of lab related investigation and subsequent warning letter and finally disqualification of laboratories.
  • Generally observed criteria for disqualification
    • Testing facility failed to comply with GLP
    • Noncompliance adversely affecting study validity
    • Other regulatory actions not effective
  • Steps followed after non-compliance is observed in a laboratory
    • Warning letter - The letter typically addresses issues like failure to maintain equipment quality, malpractice or malfunction of equipments, failure to write and follow adequate procedures for maintenance and cleaning and also issues like failure to prepare Master Production and Control Records and other observed discrepancies.
      In case of failure to rectify the discrepancies mentioned in the warning letter, next step is -
  • Disqualification - While disqualifying a facility, the FDA Commissioner specifies the reasons in a letter addressed to the top management of the facility, which are commonly:
    • The testing facility failed to comply with one or more of the regulations set forth in this part (or any other regulations regarding such facilities in this chapter);
    • The noncompliance adversely affected the validity of the nonclinical laboratory studies; and
    • Other lesser regulatory actions (e.g., warnings or rejection of individual studies) have not been or will probably not be adequate to achieve compliance with the good laboratory practice regulations.
      Usually, the facility receives an opportunity of hearing.
  1. Whenever the Commissioner has information indicating that grounds exist under Sec. 58.202 which in his opinion justify disqualification of a testing facility, he may issue to the testing facility a written notice proposing that the facility be disqualified.
  2. A hearing on the disqualification shall be conducted in accordance with the requirements for a regulatory hearing set forth in part 16 of this chapter.

Finally, after the regulatory hearing, or after the time for requesting a hearing expires without a request being made, upon an evaluation of the administrative record of the disqualification proceeding, makes the findings required in Sec. 58.202, the Commissioner issues final order for disqualification

Common Areas/processes to look for non-compliance occurrences

1.) Laboratory Equipment related issues: include problems in:

  • Calibration - The process of checking or adjusting the accuracy of a measuring instrument by comparison with a standard is known as calibration.
  • Preventative Maintenance - Preventive maintenance means providing care and servicing to maintain laboratory equipments and facilities in a satisfactory functioning condition. Purpose of this preventive action is to prevent the equipments used in the laboratory or the facility from failure in inspection through repeated detection and correction. Maintenance on the other hand, includes experiment, measurements, modification, and substitution, and is done to thwart faults before they take place.
  • Laboratory Validation - It is a process that ensures that laboratory test data and results are reliable, correct and to-the-point. Faulty validation report can lead to non-compliance of laboratory regulations.

2.) Standard Operating Procedures - SOP's: SOPs are written procedures for a laboratories program. They define how to carry out protocol-specified activities. They are written to explain how the lab procedures are supposed to work. Though there are no stipulated methods for developing SOPs, but SOPs are most of the time written in a chronological listing of action steps and include few mandatory information such as scope of the SOP, hazard assessment, assessment of exposure control, description of protective equipments. Absence of these information and others may result into failure in compliance. Following are the necessary components to ensure effective SOPs

  • Laboratory Records - Failure to keep records with right dates and reports can lead to non-compliance of laboratory regulations.
  • Data Sheets - Maintaining data sheet with accurate data and assessment of data help the facility to avoid non-compliance.

3.) Out of Specification (OOS): Trough OOS investigations, following problems can be found:

  • Laboratory Errors - These errors suggest problems in inadequate training, poorly maintained equipment, and improperly calibrated equipment.
  • Investigations - OOS investigation should be done scientifically and should be free from any bias. Target of the investigation is to inspect the containers, data and SOP.
  • Documentation - Documenting of every step of OOS investigation is important as failure to documentation may lead to non-compliance.

4.) Training: Insufficient training can raise problems in areas such as documented program, analytical method validation and reagents, solutions and reference standards.

Pre-Analytical Errors:

Pre -analytical errors tend to occur during the collection or transportation of the samples. In many cases they occur because the person who is collecting the sample fails to properly identify the patient that the sample has been collected from. It is vital that all personnel involved in these phases are fully cognizant of the risks and are trained in taking the right steps to ensure that they do not occur; this can reduce the risk of a misdiagnosis or accidental death.

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Sample Re-Analysis:
Laboratory Investigations Relating to Sample Re-Analysis will benefit laboratories, regulatory management, QA management, clinical research managers and associates, sales personnel, consultants, and quality system auditors. Understanding the procedure will help to avoid unnecessary sample re-analysis.

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Errors in Laboratory Testing:
One of the biggest issues the food and drug industry is facing today is the high number of complaints regarding the accuracy of their laboratory testing procedures. One of the major reasons for mistakes is that the laboratory testing facilities often fail to realize regulations properly and hence, fail to be complaint with them.

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Laboratory Compliance Best Practices/Standard

Good Laboratory Practice

According to the Organisation for Economic Co-operation and Development (OECD) Principles of GLP and national regulations, good laboratory practices or GLP refers to a system of management which ensures laboratories and research organizations are maintaining consistency and reliability of results. However, good laboratory practice not only is an analytical practice, but is an FDA act.

Objective of GLP is to assure quality, traceability, integrity and validity of test results. It is needed for non-clinical safety studies of developmental drugs, pesticides for agricultural purposes, toxic chemicals and to test substance of explosive hazards.

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ISO 15189

Published in 2003, ISO 15189 is on Medical laboratories - Particular requirements for quality and competence. The standard specifies need of medical laboratories to develop quality system management. Developed by the International Organisation for Standardizations' Technical Committee 212, ISO 15189 states that any laboratory to become accredited must adhere to this standard. The standard gives an in-depth focus on patient safety and addresses the importance of employee ethics in medical laboratory.

ISO/IEC 17025

Published in 2005, ISO/IEC 17025 specifies the general requirements for the competence to carry out tests and/or calibrations, including sampling. Originally known as ISO/IEC Guide 25, ISO/IEC 17025 covers testing and calibration performed using standard methods, non-standard methods, and laboratory-developed methods.

This standard is applicable to all organizations performing tests and/or calibrations. These include, for example, first-, second- and third-party laboratories, and laboratories where testing and/or calibration forms part of inspection and product certification.

Federal OSHA Hazard Communications Standard

The purpose of this section is to ensure that the hazards of all chemicals produced or imported are evaluated, and that information concerning their hazards is transmitted to employers and employees. This transmittal of information is to be accomplished by means of comprehensive hazard communication programs, which are to include container labeling and other forms of warning, material safety data sheets and employee training.

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Federal OSHA Laboratory Safety Standard

This section shall apply to all employers engaged in the laboratory use of hazardous chemicals as defined below. Uses of hazardous chemicals which do not meet the definition of laboratory use, and in such cases, the employer shall comply with the relevant standard in 29 CFR Part 1910; subpart Z, even if such use occurs in a laboratory. Procedures using chemically-impregnated test media such as Dip-and-Read tests where a reagent strip is dipped into the specimen to be tested and the results are interpreted by comparing the color reaction to a color chart supplied by the manufacturer of the test strip.

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Laboratory Permissible Exposure Limits (PELs)

OSHA sets enforceable permissible exposure limits (PELs) to protect workers against the health effects of exposure to hazardous substances. PELs are regulatory limits on the amount or concentration of a substance in the air. They may also contain a skin designation. OSHA PELs are based on an 8-hour time weighted average (TWA) exposure.

Permissible exposure limits (PELs) are addressed in specific standards for the general industry, shipyard employment, and the construction industry.

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Laboratory safety and hygiene

Chemical Hygiene Plan - Chemical Hygiene Plan is an essential part of laboratory compliance. To be compliant with laboratory guidelines, laboratory employees must understand the plan thoroughly.

Material Safety Data Sheet (MSDS) - Before using any new chemicals, employees should identify the potential risks associated with the chemical. To learn the health risks, chemical reactions, secure handling, or proper clearance process, the laboratory employee need to maintain and access the Material Safety Data Sheet.

Procedures - Before using any new apparatus or process , the lab employees must recognize the potential harms associated with the tool or process. And to recognize the potential problems, they should refer to books like "Prudent Practices in the Laboratory: Handling and Disposal of Chemicals" and "CRC Handbook of Laboratory Safety."

Spills - Laboratory employees must always know the correct response for chemical spills. Even in case of minor spills, employees should ensure that the spill does not cause chemical exposure.

Fires - For being compliant with laboratory regulations, employees should be thoroughly aware of the proper procedures of handling fire and using fire extinguishers.

Hazardous Waste - For all Hazardous Material Waste Containers, employees must ensure that they contain:

  1. LABEL indicating "HAZARDOUS WASTE."
  2. DATE indicating the first time use to collect hazardous materials.
  3. Label mentioning FULL NAMES, AMOUNTS or PERCENTAGES of the contents.

Chemical Containers - All chemical containers must contain legible labels mentioning full names of compounds. Also, it is a better practice to mention the name of the researcher and date and reference to a research laboratory notebook.

Workspace - A clean and safe workplace is mandatory in laboratory and keeping it safe and clean is the responsibility of the employee.

*Software for Laboratory Compliance

Laboratory Information Management System

LIMS (Laboratory Information Management System) is a software system used for collecting vast amount of laboratory data so they must be secure and highly reliable. Also, it helps in management of samples, laboratory users, instruments, standards and other laboratory functions such as invoicing, plate management, and workflow automation. Often IT, QA, and the users are too busy and inexperienced to implement the system, however, once this software is uploaded on your system, it will help reducing costs and implementation time; typically to one third.

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Laboratory Compliance Training:
Good Laboratory Practice Regulations
Learn FDA and International GLP regulations such as 21 CFR Part 58 and how to prepare for, conduct, and document GLP studies.
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Learning from Laboratory-related FDA Warning Letters
This presentation will cover laboratory-related warning letters that contain 483s related to regulatory issues that affes.
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Understanding and Implementing ISO 17025
Learn ISO 17025 - management, technical and documentation requirements. The strategies for ISO 17025 cost effective implementation and benefits, steps towards ISO 17025 laboratory accreditation, and ISO 17025 audit.
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Investigating Out of Specification Guidance (OOS) in the Laboratory
Understand the requirements and interpretation of investigational results of Out-of-Specification (OOS) in the laboratory and comply with FDA's OOS final guidance document entitled Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production.
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cGMP 'Pitfalls' in the QC Laboratory-Preparing the QC Laboratory and Staff for an FDA Inspection
The principles of GMP compliance for improved laboratory performance and overall compliance and train the Laboratory staff for an Inspection as well.
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LIMS (Laboratory Information Management System) Validation in One Third the Time
Learn how to reduce costs and software implementation time and how to avoid 483s and warning letters.
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Good Laboratory Practices (GLP): Documenting Deviations & Unexpected Circumstances
Discover the importance of documentation of deviations and unexpected circumstances and responsibilities of study director, principal investigator, QA and management.
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Decoding CLIA (Clinical Laboratory Improvement Amendments) Regulations: Calibration, Calibration Verification and Method Validation - Learn about CLIA standards for frequency, and its methodology of implementation and also meaning of calibration, calibration verification and method validation. More Info
System Based Inspections - Laboratory Controls
Learn what is Systems Based Inspection and its difference from the old inspectional techniques.
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CLIA (Clinical Laboratory Improvement Amendments) Guidelines on Quality Control and Quality Assessment
Understand the differences and the proper methods to meet the Clinical Laboratory Improvement Amendments (CLIA) guidelines. Identify the difference between Quality Assurance and Quality Assessment.
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Auditing the QC Microbiology Laboratory for FDA Compliance
This webinar will provide a comprehensive overview of the infrastructure of a compliant microbiology testing laboratory, preparation for an inspection, potential areas for nonconformance, test failures, resolution of audit findings, and examples of issuance of 483s and warning letters.
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Understanding and Preparing for System Based Inspections: Laboratory Control System
Prepare for your Pre-Approval Inspection (PAI). Review the elements of the Laboratory Control System, examine examples of FDA 483 observations and understand how FDA conducts systems based inspections.
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Out-of-Specification Investigations, Identifying the Attributable cause or Laboratory Error
This webinar will guide you through initial laboratory investigation which follows the FDA guidance; Guidance for Industry: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production.
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Laboratory Investigations Relating To Sample Re-Analysis: Covering the Basics before Being Called Out
This webinar provides guidance on procedures investigating unexpected results for Non-Clinical and Clinical Trials and will discuss several suggested procedures, avoiding unnecessary re-analysis.
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Strategies to Establish and Manage a Compliant Contemporary Microbiology Laboratory
Gain a comprehensive overview of Auditing of a Microbiology Laboratory for QC compliance and microbiology testing laboratory in accordance with current global regulatory (FDA, ICH and CDC) directives.
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Setting up a cGMP compliant Microbiology Laboratory
Understand the best practices related to microbiology laboratory programs, the equipment needs, testing controls, trainings and OOS investigations for setting up a microbiology laboratory.
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Out-of-Specification Investigations - Beyond the laboratory
Out-of-Specification Investigations webinar will begin with the confirmed out-of-specification laboratory result and discuss how the investigation is expanded into the whole organization.
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The CLIA Laboratory Inspection: Failure is not an Option
Learn features of laboratory inspection as per CLIA inspection guidelines.
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Engineering and Laboratory Mythology with Water System
Understand the myths surrounding microbial monitoring and control approaches and be aware of the pitfalls of believing these myths which could cause over-confidence in a system's design for microbial control or the suitability of your microbial test methods.
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Preparing for and handling FDA Laboratory GMP inspections
The webinar provides an overview of FDA GMP Inspection process and trains how to prepare for inspections procedures during and after an inspection.
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Good Laboratory Practice Regulations - Introduction and Strategies for Implementation
Learn what GLP is, who has to comply, differentiations of US and International regulations on GLP, how to archive GLP data, document GLP and protocols.
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Laboratory Investigation Out-of-Specification Results
Learn what constitutes an OOS observation, what are the guidance's processes & steps to be taken in the laboratory in the event of an OOS observation.
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