Checklist for Laboratory in Pharma Industry
Laboratories should be audited regularly and at least once per year.
Auditing is an independent activity and separate from self-inspection.
Auditing activities could include reviewing SOPs, worksheets, laboratory notebooks, balance calibration records,
working control data, pipette calibration records, equipment monitoring logs and other related items for producing test results.
The auditor should use a checklist to determine the auditing scope and content (and example of such a checklist is detailed below).
The audit results then initiate corrective and/or preventive action to ensure continuous improvement of the quality
Based on past results and a review of laboratory performance (such as the number of deviations or out-of-specification reports), the auditor may elect to focus on specific areas (such as a test method) or a more general review of the laboratory, such as tracking the path of a sample from receipt through testing and to final reporting.
These different approaches will often rest upon risk and a risk-based approach to auditing.
It is important that the person tasked with auditing the laboratory has an understanding of laboratories is general and Ideally of the specific function of the laboratory.
During the audit the auditor should observe, check the documentation, and also listen to what is being said (interestingly, the word audit is derived from a Latin word “audire” which means “to hear”).
The laboratory itself should prepare for the audit in advance, such as by:
Planning thoroughly and carefully
Organizing everything ahead of time, including documents and records, to save valuable time during the audit.
Making sure all staff aware of the audit and arranging schedules so that all staff needed for the audit will be available.
The laboratory must be managed correctly, with the appropriate trained and qualified people in place. In addition, there must be a clear management function, with personnel and different levels of responsibility and seniority.
Management should have a focus on laboratory process control, which should include quality control for testing, appropriate management of the sample, including collection and handling, and method verification and validation.
The laboratory should establish, implement and maintain a management system appropriate to the scope of its activities.
The laboratory must document its policies, systems, programs, procedures and instructions to the extent necessary to assure the quality of the test and/or calibration results.
The system’s documentation needs to be communicated to, understood by, available to, and implemented by the appropriate personnel.
With management, the laboratory should have managerial and technical personnel who have the authority and resources needed to carry out their duties including the implementation, maintenance and improvement of the management system and to identify the occurrence of departures from the management system or from the procedures for performing tests and/or calibrations, and to initiate actions to prevent or minimize such departures.
Furthermore, laboratory management should provide adequate supervision of testing and calibration staff, including trainees, by persons familiar with methods and procedures, purpose of each test and/or calibration, and with the assessment of the test or calibration results.
In addition, they should have technical management which has overall responsibility for the technical operations and the provision of the resources needed to ensure the required quality of laboratory operations.
Good Laboratory Design
The laboratory must be appropriately designed laboratory to enable appropriate workflow and to avoid cross-contamination or mix-up of samples.
This will include dedicated work areas and materials of construction, such as workbenches being built of materials that are durable and easy to disinfect.
Furthermore, access to rooms where manipulation or analysis of samples takes place, or where hazardous chemicals or other materials are stored.
As part of good design principles, the laboratory must have systems to monitor, control, and record environmental conditions as required by the relevant specifications, methods and procedures or where they influence the quality of the results.
Due attention should be paid, for example, to biological sterility, dust, electromagnetic disturbances, radiation, humidity, electrical supply, temperature, and sound and vibration levels, as appropriate to the technical activities concerned.
Management need to ensure that tests and calibrations are stopped when the environmental conditions jeopardize the results of the tests and/or calibrations.
There should be effective separation between neighboring areas in which there are incompatible activities. Measures must be taken to prevent cross-contamination and access to and from laboratory areas dealing with the tests and/or calibrations need to be controlled.
The laboratory must determine the extent of control based on its particular circumstances. Further, measures
need be taken to ensure good housekeeping in the laboratory.
The laboratory management should have mechanisms in place to ensure the competence of all who operate specific
equipment, perform tests and/or calibrations, evaluate results, and sign test reports and calibration certificates.
When using staff who are undergoing training, appropriate supervision needs to be provided.
Personnel performing specific tasks are to be qualified on the basis of appropriate education, training, experience, and/or demonstrated skills, as required.
Well-operated equipment and instruments reduce variation in test results and improve the laboratory’s confidence in the accuracy of testing results.
Hence, it is important that laboratory results are of required quality and this will often rest upon the suitability of the instrumentation, and whether instrument calibration has been conducted. In addition to calibration, regular verifications are required to ensure that measurements are accurate, such as verification of balances or pipettors.
To support these requirements, an equipment management program should be in place to address equipment selection, preventive maintenance, and procedures for troubleshooting and repair.
Sample management is a key part of process control. Importantly, the quality of the work a laboratory produces is only as good as the quality of the samples it uses for testing. The laboratory needs to be proactive in ensuring that the samples it receives meet all of the requirements for producing accurate test results.
This means there need to be sample records that show chain-of-custody. Records can be manual, e.g., forms or logbooks, or electronic, e.g., LIMS (laboratory information management system).
In addition, samples need to be stored in an area that maintains their quality.
This includes areas that are properly identified, clean and orderly, and is adequate to prevent mix-up and contamination from other samples, from chemicals and reagents, and from spillage.
An important area is with sample labeling.
Each sample should be clearly labeled with:
- Unique identification numbers
- The test that has been requested
- The time and date of collection
- The sample expiry time
- Sample storage conditions
- Identification of the person who collected the sample
This leads into sample receipt:
Verifying the sample is properly labeled, adequate in quantity, in good condition, and appropriate for the test
The test request must be complete and include all necessary information.
Recording sample information into a register or log.
Enforce procedures for storing the sample prior to the test (location, time, temperature, ensuring sample segregation etc.) And then logging in the sample, recording either manually or electronically:
- Date and time of collection,
- Date and time the sample was received in the laboratory,
- Sample type,
- Tests to be performed.
- Description of what samples should be stored;
- Retention time;
- Conditions for storage, such as atmospheric and temperature requirements;
System for storage organization—one method is to store samples by day of receipt or accession number.
The laboratory must have a system in place to allow for tracking a sample throughout the laboratory from the time it is received until results are reported.
There should also be a process in place for rejecting samples.
Samples could be rejected, for instance, due to:
- An unlabeled sample Broken or leaking tube/container
- Insufficient information
- Sample label and accompanying record do not match
- Sample collected in wrong tube/container
- Sample stored incorrectly
- Sample time expired
- Inadequate volumePoor handling during transport
Traceability, Uncertainty, and Proficiency Testing Traceability, uncertainty and proficiency testing are the three important areas to be addressed in an audit.
Traceability is about gaining the assurance that the measurement results can be related to a reference through a documented, unbroken chain of comparisons. For example, the bias, precision, and accuracy of testing can be determined by testing a certified reference material and comparing the laboratory results with the certified value.
The certified value of the reference material is generally reported with uncertainty such that the comparison is of statistical significance.
Proficiency tests serve as the external quality assurance, assuming the laboratory participates in a proficiency sample test program organized outside of the laboratory.
Proficiency testing is an interlaboratory comparison, in which a number of laboratories conduct testing methods within their own lab on the same material and report the results to the organizing party.
Each individual laboratory is then evaluated for performance based on statistical calculations.
To establish required proficiency, the laboratory needs to maintain an appropriate schedule to participate in a proficiency test program.
Reference Standards and Controls
The laboratory must establish a quality control program for all quantitative tests. Evaluating each test run in this way allows the laboratory to determine if patient results are accurate and reliable.
This will be achieved using appropriate reference standards, and the suitability and verification of reference standards should be assessed as part of an audit.
The audit should also consider the controls run with each test. Controls are substances that contain an established amount of the substance being tested—the analyte.
Controls are tested at the same time and in the same way as test samples.
The purpose of the control is to validate the reliability of the test system and evaluate the operator’s performance and
environmental conditions that might impact results.
The auditor should consider:
If controls are appropriate for the targeted diagnostic test—the substance being measured in the test must be present
in the control in a measurable form.
The amount of the analyte present in the controls should be close to the decision points of the test; this means that
controls should check both low values and high values.
Controls should have the same matrix as the test sample.
For quantitative testing, statistical analysis is often used for the monitoring process, such as the use of Levey–Jennings charts.
The source of the control material should be considered: control materials may be purchased, obtained from a central or reference laboratory, or made in-house.
Purchasing and Supplier Approval The laboratory should have a policy and procedure(s) for the selection and purchasing of services and supplies it uses that affect the quality of the tests and/or calibrations.
Procedures should exist for the purchase, reception and storage of reagents and laboratory consumable materials relevant for the tests and calibrations.
The laboratory needs to ensure that purchased supplies and reagents and consumable materials that affect the quality of tests and/or calibrations are not used until they have been inspected or otherwise verified as complying with standard specifications or requirements defined in the methods for the tests and/or calibrations concerned. These services and supplies used need to comply with specified requirements and records of actions taken to check compliance are to be maintained.
An efficient laboratory requires good quality records and procedures. In this context “document” could be policy statements, procedures, specifications, calibration tables, charts, text books, posters, notices, memoranda, software, drawings, plans, etc.
These may be on various media, whether hard copy or electronic, and they may be digital, analog, photographic or written.
All documents issued to personnel in the laboratory as part of the management system should have been reviewed and approved for use by authorized personnel prior to issue.
With standard operating procedures these must be clear instructions as to ensure consistency:
everyone should perform the tests exactly the same way so that the same result can be expected from all staff.
Such procedures should also ensure accuracy, since following written procedures helps laboratory staff produce more accurate results than relying on memory alone because they will not forget steps in the process.
The objective is to achieve a consistent (reliable) and accurate result.
Records should be available for all aspects of the laboratory function.
These can be manual or computerized and they will contain are the collected information produced by the laboratory in the process of performing and reporting a laboratory test.
Characteristics of records are that they need to be easily retrieved or accessed and that they contain information that is permanent and does not require updating.
- Sample logbooks
- Sample registers
- Laboratory workbooks or worksheets
- Instrument printouts
- Equipment maintenance records
- Quality control data
- External quality assessment or proficiency testing records
- Training records
- Results of internal and external audits
- Out-of-specification reports
- Incident reports
Test records must contain key information, such as :
- Identification of the test
- Identification of laboratory
- Unique identification and location of the sample
- Date and time of collection, and time of receipt in laboratory
- Date and time of release of report
- Primary sample type
Results reported in SI units or units traceable to SI units, where applicable
Reference materials, where applicable The test result, reported in appropriate units of measurement Interpretation of results, where appropriate Applicable comments relating to quality or adequacy of sample, methodology limitations, or other issues that affect interpretation
Identification and signature of the person authorizing release of the report If relevant, notation of original and corrected results If the record is a copy, that it is a certified copy of the original With manual forms these should be authorized in advance and serialized, so that each test record had a unique identifier.
All laboratory documents need to be controlled. A system must be established for managing them so that current versions are always available.
A document control system provides procedures for formatting and maintaining documents.
The auditor should assess whether there are outdated documents in circulation if there are any document distribution problems and if there are any external documents that are not being properly controlled. Control also extends to storage and archiving.
Data and Computerized Systems in Pharma Industry
Data integrity is an important area, applying both to paper records and automated systems.
Information systems include the management of data and records contained in both computer and non-computerized systems.
Laboratory management must ensure that documented procedures for sample collection, indexing, access, storage, maintenance, amendment and safe disposal of quality and technical records are in place, among other more specific test activities.
Such procedures must guarantee that the laboratory has access to the data and information necessary to provide a service which meets the needs and requirements of the user.
Electronic systems should also have:
Permanence—backup systems are essential in case the main system fails.
Additionally, regular maintenance of the computer system will help to reduce system failures and loss of data Security— password protection with multiple user levels of access.
Traceability— electronic record systems should be designed in a way that allows for tracing the sample throughout the entire process in the laboratory Audit trails
Trending and Controls
Much of quality control is concerned with measurements or at least an assessment of a result against predetermined limits.
Where discrete results are produced, the laboratory should be undertaken trend analysis (such as by using statistical process
control) (17). Such approaches involve the application of statistical methods to evaluate variability in the laboratory testing.
Control charts provide the best means by which to monitor the testing procedures. In analytical laboratories, control charts are
produced by calculating the long-term mean and range by averaging multiple sets of experimental duplicates over time (18).
Through this, the laboratory can put in place a system to establish an expected average and variation for future comparison.
Control charts thus provide a standard against which the stability of the laboratory performance can be evaluated, and they
should feature within the audit.
Laboratory Non-Conformances in Pharma Industry
The laboratory must have a policy and procedures that that is be implemented when any aspect of its testing and/or calibration
work, or the results of this work, do not conform to its own procedures or the agreed requirements of the customer. The policy
and procedures must ensure that:
The responsibilities and authorities for the management of nonconforming work are designated and actions (including
halting of work and withholding of test reports and calibration certificates, as necessary) are defined and taken when
nonconforming work is identified
An evaluation of the significance of the nonconforming work is made
correction is taken immediately, together with any decision about the acceptability of the nonconforming work
Where necessary, the customer is notified, and work is recalled
The responsibility for authorizing the resumption of work is defined
In addition, the laboratory would have needed to establish a policy and procedure and should designate appropriate
authorities for implementing corrective action when nonconforming work or departures from the policies and procedures in the
management system or technical operations have been identified. A problem with the management system or with the
technical operations of the laboratory can be identified through a variety of activities, such as control of nonconforming work,
internal or external audits, management reviews, feedback from customers and from staff observations. Furthermore, when
improvement opportunities are identified or if preventive action is required, action plans should be developed implemented and
monitored to reduce the likelihood of the occurrence of such nonconformities and to take advantage of the opportunities for
Self-Inspection / Self-Audit in Pharma Industry
The laboratory should periodically, and in accordance with a predetermined schedule and procedure, conduct internal audits
of its activities to verify that its operations continue to comply with the requirements of the management system. The internal
audit program should address all elements of the management system, including the testing and/or calibration activities. It is
the responsibility of the quality manager to plan and organize audits as required by the schedule and requested by
management. Such audits need to be carried out by trained and qualified personnel who are, wherever resources permit,
independent of the activity to be audited.
Other important considerations for the audit include the use of reference materials, repeated analyses, and sample and
reagent blank analyses.
CHECKLIST FOR AUDITING THE LABORATORY in Pharma Industry
Below is an example checklist that can be used or adapted for auditing a laboratory function. The checklist is aimed at the
quality control laboratory function. When considering the checklist, the following framing questions may be useful:
What procedures and processes are being followed in the laboratory
What is being done at the time and against which procedure?
Do the current procedures and processes comply with written policies and procedures?
Are there written policies and procedures for each activity?
Do written policies and procedures comply with appropriate standards, regulations, and requirements?
The checklist below consists of example area are audit questions that could be asked.
Are there a nominated manager & deputy who are suitably qualified and experienced?
Is there a suitably qualified quality control manager responsible for all quality control activities in the laboratory?
Is the laboratory appropriately accredited?
Are the methods for analysis of parameters of interest accredited?
With laboratory management, the system should cover work carried out in the laboratory’s permanent facilities, at sites
away from its permanent facilities, or in associated temporary or mobile facilities (if applicable).
Is the laboratory manager supported by an adequate number of qualified staff, trained in the principles and practice of
relevant areas of analysis;
Is a training procedure in place for laboratory staff? (This procedure should cover both analytical procedures and the
relevant principles and practice of analysis, including calibration and internal and external analytical quality control)
Do the training procedures set criteria and method of assessment of the competence of staff to conduct analysis?
Are staff training records in place and kept up to date? (a training record should set out clearly those procedures and
practices in which staff have been trained, the dates and results (competency) of that training, the dates and results of
audits of training and any re-training and the results of any annual review)
Laboratory Quality Systems
Is a documented quality manual in place?
Is the quality manual based on appropriate the requirements (according to a local or international at standard)?
Does the quality manager conduct audits to assess compliance with systems and methods? (these audits should be
The laboratory should have a sampling plan and procedures for sampling when it carries out sampling of substances,
materials or products for subsequent testing or calibration.
The sampling plan as well as the sampling procedure must be available at the location where sampling is undertaken.
Sampling plans must, whenever reasonable, be based on appropriate statistical methods. The sampling process will
address the factors to be controlled to ensure the validity of the test and calibration results.
Sampling procedures should describe the selection, sampling plan, withdrawal and preparation of a sample or samples
from a substance, material or product to yield the required information.
Does the laboratory have procedures for recording relevant data and operations relating to sampling that forms part of
the testing or calibration that is undertaken? (These records should include the sampling procedure used, the
identification of the sampler, environmental conditions (if relevant) and diagrams or other equivalent means to identify
the sampling location as necessary and, if appropriate, the statistics the sampling procedures are based upon).
Sample Shipment, Receipt and Storage
Is there a SOP for sample receipt, shipment and storage of materials and test samples?
Does the SOP contain a chain of custody procedure?
Is the sample receipt area maintained separate from the sample processing area?
Reference materials should be traceable to SI units of measurement, or to certified reference materials.
Internal reference materials must be checked. Checks are needed to maintain confidence in the calibration status of
reference, primary, transfer or working standards and reference materials.
Are tests conducted according to authorized procedures?
Are tests appropriate for the sample being tested?
Are appropriate controls in place?
Are results independently checked?
Are there an assay validation, re-validation and limited validation process outlined in a SOP?
Is there a written procedure for repeat testing or invalidating lab data? Is there a repeat decision tree?
How are results that fail specifications investigated or non-conformances investigated?
Are there validated methods and acceptance criteria for each test method?
Is there a SOP for significant figures?
Is there a SOP that outlines good documentation practices?
Reagent and Solution Labeling and Qualification
Is there an SOP that outlines how reagents are labeled, how expiration dates are established?
Are reagents qualified for use? Is parallel testing of reagents performed?
Is there a current inventory of all reagents and solutions?
Does a documentation control system exist and is it functional?
Is raw laboratory data recorded in lab notebooks, electronically, or controlled data sheets?
Are laboratory final reports generated for clinical studies?
Who reviews the reports?
Is there a SOP that outlines the content of the final report?
Is there a SOP or a system for the retention, storage, and destruction of records?
Test reports should, where necessary for the interpretation of the test results, include the following:
deviations from, additions to, or exclusions from the test method, and information on specific test conditions,
such as environmental conditions;
where relevant, a statement of compliance/non-compliance with requirements and/or specifications;
where applicable, a statement on the estimated uncertainty of measurement; information on uncertainty is
needed in test reports when it is relevant to the validity or application of the test results, when a customer’s
instructions so require, or when the uncertainty affects compliance to a specification limit;
where appropriate and needed, opinions and interpretations ;
additional information which may be required by specific methods, customers or groups of customers.
Test reports containing the results of sampling should include the following, where necessary for the interpretation of test results:
the date of sampling;
unambiguous identification of the substance, material or product sampled (including the name of the manufacturer, the model or type of designation and serial numbers as appropriate);
the location of sampling, including any diagrams, sketches or photographs;
a reference to the sampling plan and procedures used;
details of any environmental conditions during sampling that may affect the interpretation of the test results;
any standard or other specification for the sampling method or procedure, and deviations, additions to or
exclusions from the specification concerned.
- Is there a dedicated facility/area for the archival of records?
- Is there control access to the archival facility?
- Is the environment of the facility monitored and controlled?
- Is the procedure for archiving records outlined in an SOP?
- Is the retention time for records stated in the SOP?
- Is there a method of electronic data archive?
Is access to computers limited by an individual username and password system (lab members cannot share a
How is the computer network and computer systems maintained, if applicable?
Are there a computer validation master plan and/or SOPs?
List computers systems and software utilized. Validated?
Are changes to computer systems controlled and documented?
Are records of computer system errors maintained and investigated?
Are records of hardware maintenance and repairs maintained?
Are computers backed up routinely to prevent loss of data? Is there a backup log?
Is there a preventative maintenance program for computer systems?
Equipment & Calibration
Is a documented calibration program in place for all necessary equipment? (As well as major pieces of instrumentation this should include small laboratory items e.g. pipettes, ovens)
Are calibration records current for all equipment and maintained on file?
Has traceability of the calibration been established to relevant SI units of measurement?
Is a documented maintenance program in place in accordance with the manufacturer’s/suppliers ’ recommendations for equipment utilized?
Are laboratory facilities appropriate for the range of tests carried out?
Is laboratory equipment located and utilized in an appropriate manner?
Is the equipment and its software used for testing, calibration and sampling capable of achieving the accuracy required and must comply with specifications relevant to the tests and/or calibrations concerned?
Have calibration programs been established for key quantities or values of the instruments where these properties
have a significant effect on the results?
Before being placed into service, has equipment (including that used for sampling) been calibrated or checked to
establish that it meets the laboratory’s specification requirements and complies with the relevant standard
Has equipment been operated only by authorized personnel?
Are up-to-date instructions on the use and maintenance of equipment (including any relevant manuals provided by the manufacturer of the equipment) available for use by the appropriate laboratory personnel?
Has each item of equipment and its software used for testing and calibration and significant to the result should, when practicable, been uniquely identified?
Are records maintained for each item of equipment and its software significant to the tests and/or calibrations
The auditor should check that the records include at least the following:
- the identity of the item of equipment and its software;
- the manufacturer’s name, type identification, and serial number or other unique identification;
- check that equipment complies with the specification;
- the current location, where appropriate;
- the manufacturer’s instructions, if available, or reference to their location;
- dates, results and copies of reports and certificates of all calibrations, adjustments, acceptance criteria, and the
due date of next calibration;
- the maintenance plan, where appropriate, and maintenance carried out to date;
- any damage, malfunction, modification or repair to the equipment.
Has equipment that has been subjected to overloading or mishandling, gives suspect results, or has been shown to be
defective or outside specified limits, been taken out of service? (equipment should be isolated to prevent its use or
clearly labeled or marked as being out of service until it has been repaired and shown by calibration or test to perform correctly).
Do calibration certificates include:
- the conditions (e.g., environmental) under which the calibrations were made that have an influence on the
- the uncertainty of measurement and/or a statement of compliance with an identified metrological specification
or clauses thereof;
- evidence that the measurements are traceable.
Ensure the calibration certificate relate only to quantities and the results of functional tests.
If a statement of compliance with a specification is made, this must identify which clauses of the specification are met or not met.
If an instrument for calibration has been adjusted or repaired, the calibration results before and after adjustment or
repair, if available, should be reported.
Are documented standard operating procedures in place for each test method?
Are all relevant procedures based on reference standard methods (as defined in the license)?
Is a copy of relevant standards available on-site?
For analytical laboratories, does the laboratory have in place procedures for estimating uncertainty of measurement?
Control of Data
Are calculations and data transfers e subject to appropriate checks in a systematic manner?
When computers or automated equipment are used for the acquisition, processing, recording, reporting, storage or
retrieval of test or calibration data, has the laboratory ensured that computer software developed by the user is
documented in sufficient detail and is suitably validated as being adequate for use?
Have procedures been established and implemented for protecting data; such procedures should include, but not be
limited to, integrity and confidentiality of data entry or collection, data storage, data transmission and data processing?
Are computers and automated equipment maintained to ensure proper functioning and are provided with the
environmental and operating conditions necessary to maintain the integrity of test and calibration data?
Ask how samples are logged in and stored.
Does the sample logbook (or another record) provide spaces for who delivered the sample and who then took it for
testing (chain of custody)?
What type of samples might be temporarily stored while awaiting testing?
What method validation or compendial reference supports the sample storage conditions (e.g., water)?
What site SOP governs what happens when a sample time point is missed? (should be a deviation).
If LIMS is used for tracking all samples and activities, check if pen raw data precedes computer and whether the
former is properly retained.
Where applicable, has laboratory in place procedures for safe handling, transport, storage, use, and planned
maintenance of measuring equipment to ensure proper functioning and in order to prevent contamination or
Laboratory Quality Control – Internal Controls
Does the Laboratory have a documented internal quality control procedure in place?
Are all relevant methods subject to internal quality control?
Are quality control outputs subject to evaluation (such as charts maintained, are actions taken upon failure)?
Are acceptance criteria set for quality control fit for purpose?
Laboratory Quality Control – External Controls
Is the laboratory a participant in a laboratory proficiency scheme e.g. Aqua Check or EPA proficiency scheme?
The results of any analysis submitted has part of a proficiency should be checked, if any samples failed the criteria set
by the scheme, procedures should be in place to conduct an investigation)
Are procedures in place to deal with proficiency scheme failures?
Laboratory method validation is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled.
Is a written methodology in place to determine the performance characteristics of test methods under the following
Is method qualification assessed for:
Limit of Quantitation,
Uncertainty of Measurement,
Range & Linearity and
To verify all the documented procedure in place to determine the suitability of the procedure for test matrices.
To check all the relevant test methods been assessed for their suitability to the test matrix.
To verify all the introduction of test and calibration methods for its own use a planned activity is developed by the laboratory?
To verify all the validation activities assigned to qualified personnel equipped with adequate resources.