Good Clinical Laboratory Practice

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Good Clinical Laboratory Practice (GCLP) is an international quality assurance system within the framework of the GxP for laboratories that carry out the analysis of samples from clinical studies .

The main purpose of GCLP is to provide quality system guidance that can be used internationally by organizations and individuals who perform analysis of samples from clinical trials. How the facilities, systems and procedures, the quality and integrity of the work and the results generated.

Since GCP does not define any requirements for test laboratories and GLP was developed for pre-clinical trials and therefore does not deal with the special treatment of human laboratory samples from clinical studies, a guideline was proposed by the British Association of Research Quality Assurance (BARQA) in 2003 to close this gap should. Later the WHO and the UK health authority MHRA issued their own versions of a GCLP guideline. Since February 2012 there has also been a Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples from the European Medicines Agency (EMA).

definition

Good Clinical Practice (GCP): is an international ethical and scientific quality standard for the development, implementation, recording and reporting of studies that affect human participation. Good Clinical Practice (GCP) has been implemented into the regulations of many countries to ensure public safety that the rights, safety and well-being of test subjects are protected.

Good Laboratory Practice (GLP) comprises the organizational process and the conditions under which laboratory studies are planned, carried out, monitored, recorded and reported. It is a concept to ensure the reliability and integrity of the data by the GLP (Good Laboratory Practice, Good Laboratory Practice applies specified) standards, while ensuring that the goals and objectives of GCP regulations are met. The implementation of GCLP provides a uniform guideline that can be applied globally to clinical sample analysis. This facilitates patient safety and confidence in the data generated. This promotes the mutual acceptance of clinical data by regulatory authorities worldwide.

Good Clinical Laboratory Practice (GCLP) is a GxP guideline for laboratory samples from clinical studies . Since GCP does not define any requirements for test laboratories and GLP was developed for pre-clinical trials and therefore does not deal with the special treatment of human laboratory samples from clinical studies, a guideline was proposed by the British Association of Research Quality Assurance (BARQA) in 2003 to close this gap should. Later the WHO and the UK Health Authority MHRA issued their own versions of a GCLP guideline. Since February 2012 there has also been a Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples from the European Medicines Agency (EMA).

aims

In any object that is publicly available, any claim to the presence of certain beneficial properties or the absence of harmful influences can either be trustworthy or checked by a mechanism. The responsible authorities must ensure that the safety of the products has been proven and that these safety claims can be checked. Such verification is obtained either by repeating the experiment itself or by fully, step-by-step reconstruction of all the activities and circumstances carried out that led to the result that was to be verified. So GCLP was introduced to ensure data quality and integrity.

GCLP guidelines

Organization and staff

Laboratory management tasks

The laboratory management should ensure that the principles of the GCLP are adhered to in the laboratory , thereby ensuring general compliance with the GCP. The person who will perform the laboratory management role should be identified.

The laboratory management should:

  1. ensure that qualified personnel, adequate facilities, equipment and materials are available;
  2. a record of the qualifications, training, experience and job descriptions for each individual working in the experimental facility;
  3. ensure that staff clearly understand the tasks of their job and, if necessary, receive training for these tasks;
  4. ensure that health and safety measures are applied in the test facility in accordance with national and / or international standards and rules;
  5. ensure that adequate SOPs are implemented and followed and that a record exists of all these SOPs;
  6. ensure there is a quality audit program in place with designated staff;
  7. ensure that, and when appropriate, a quality control program is carried out at the experimental facility;
  8. Ensure that there is an analysis plan that defines the analyzes to be performed by the facility. This instruction can be included as part of the test protocol;
  9. ensure that any changes to the analysis plan have been accepted and documented;
  10. Make copies of all experimental protocols and analytical plans;
  11. ensure that a sufficient number of personnel are available to conduct the work in a timely and competent manner;
  12. for each trial, identify an individual with appropriate qualifications, training and experience from the analysis project manager prior to commencing work in the trial facility;
  13. ensure that an individual or an association is identified as responsible for managing the archives used to hold the experimental and facility records;
  14. for any work that has been subordinated by the experimental facility, the experimental facility management is responsible to the sponsors for its direction.

Project manager tasks

The project manager is responsible for any and all of the analyzes carried out by the experimental facility and for its report. This responsibility should include, but not be limited to, the following functions:

  1. agree to the dated, signed analysis plan;
  2. ensure that the procedures outlined in the analysis plan are followed and that authorization for each change has been received and documented along with the reasons for it;
  3. ensure that all analysis results are fully documented and recorded;
  4. sign and date all analysis reports; obtain responsibility for the validity of the results and confirm compliance with guidelines of good clinical laboratory practice, if required;
  5. if the analysis results are published, the analysis project manager should ensure that these results are only published dated and signed by an authorized signature;
  6. ensure that after the completion of the analyzes, the analysis plan, the analysis report and / or the analysis results, the original data and supporting documentation are archived and retained;

Trial Workforce Responsibilities

  1. All staff who work with experimental materials should be aware of the guidelines that apply to their work.
  2. The entire workforce is responsible for the prompt, accurate, and compliance with these guidelines of recording the original data and is responsible for the quality of their data.
  3. The entire workforce is responsible for following the instructions given in the test protocol, analysis plans and operating instructions.

Facilities

This part consists of:

  • Laboratories: The laboratory should be of suitable size, construction and location to meet the requirements of the study and to minimize any interference that could affect the validity of the study or its results. It should also have adequate facilities of sufficient size for the type of work being carried out and with a sufficient level of separation and security to ensure the integrity of the samples at all times.
  • Archive facilities:
  1. Where appropriate, space should be provided for the secure archiving and retrieval of data, reports, samples and specimens.
  2. If suitable facilities are unable to provide storage space for the test records, alternative arrangements can be made. This could include the use of third party contractors.

Equipment, materials and reagents

This part consists of:

3.1 Equipment

  1. Equipment used for the analysis of test samples and for the operation of the laboratory should be appropriately set up in an appropriate manner and with adequate design and capacity.
  2. It should be cleaned, maintained and calibrated accordingly. Maintenance records and unforeseen maintenance or calibration should be retained.
  3. A maintenance plan that includes all relevant equipment and a schedule for planned services and calibrations should be maintained.
  4. All equipment that is out of service should be marked as such.
  5. Users of work equipment should be qualified and trained in the use of the corresponding work equipment.
  6. In any case, the equipment used should demonstrably serve the purpose

3.2 Materials

  1. The materials used should be stored appropriately for the purpose.

3.3 reagents

  1. The reagents should be appropriately labeled and indicate identity, concentration, specific storage instructions and shelf life. The best before information can include the date of manufacture and the earliest expiry date.

Standard Operating Procedures (SOPS)

4.1 General

  1. A laboratory should document the Standard Operating Procedures (SOPs) approved by the laboratory management , which are intended to guarantee the quality and integrity of the work carried out and the data generated.
  2. SOPs should be reviewed regularly to ensure they remain current and current.
  3. A list of the current SOPs, including the version number, should be kept up to date.
  4. The laboratory staff should have SOPs immediately available for the activities carried out there. Published textbooks, articles and manuals can be used to supplement these SOPs, provided that they are retained.

4.2 Application

  1. Standard Operating Procedures (SOPs) should at least be available for the following activities. The details under the heading are illustrative examples.

a) Sample deliveries

Delivery, preparation, labeling, handling, shipping, storage

b) Equipment

Workflow, maintenance, cleaning, calibration

c) Archiving, documentation, storage and retrieval of data

Coding of experiments, data collection, preparation of reports, indexing systems, handling of data, use of electronic data systems and archiving

d) test materials

Storage, query and test chain of test material

e) Preparation of sample packs

f) Measures for the receipt, transfer, sampling, storage, identification and maintenance of the test materials and samples

g) Measures for the analysis of test material

h) Quality control measures

Quality control measures are carried out by the testing facility to ensure the accuracy and quality of the results

i) Measures for quality audit

The job of the quality audit staff is to carry out test audits, inspections and analytical reports and to document them in writing.

Planning the work

This part consists of:

  • Analytical plan:

1- For each study in which the laboratory is involved, a written analysis plan should be drawn up before the start of the project.

2- The analysis plan should describe the work to be performed by the laboratory and should be available to the staff involved in this work.

3- This plan should be an accurate reflection of the requirements set out in the clinical protocol and only the work required by the informed consent of the study subjects.

4- This plan should be agreed upon by the dated signature of the analytical project leader and sponsor .

5- The analytical plan can be a controlled document or part of the contractual agreement with the sponsor or it can be included in the clinical protocol.

6- The analytical plan should be kept as part of the laboratory records for the study.

7- Any changes or revisions to the agreed analytical plan should be documented, including justification (s), and agreed by the dated signature of the analytical project leader and sponsor. Copies of all changes should be kept with the original analysis plan.

  • Content of the analytical plan: The analytical plan should be detailed enough to give clear guidance to the workers who carry out the work beyond what is required. An example of this is the identification of work.

Sub-contracting

In order to maintain the GCLP for all work, prior to subcontracting work, warranty should be obtained to confirm that the subcontractor is working in accordance with GCP, GCLP and all testing requirements.

The subcontracting agreement should clearly define the roles and responsibilities, the details of the analyzes to be carried out and the storage of sample data.

Experimental materials

Guidelines for receiving and correctly handling test materials are described here.

reception

1- Procedures for the receipt, handling, storage , recovery and management of test materials should be designed in such a way as to avoid confusion and to maintain their completeness. Test samples should be sufficiently identified at all times .

2- Test materials should be checked upon receipt to ensure their identification. Records of identity, source, arrival date and condition on arrival should be kept.

Test chain

1- Facilities and processes should be designed and implemented in such a way that the identification and traceability of test materials is guaranteed at all times.

2- Reports should be prepared in order to guarantee the reconstruction of the test chain of the test materials received and to enable the subsequent evaluation of material stores.

3- Storage sites of test materials should be monitored where controlled conditions are necessary to ensure the completeness of the test material.

Contingency plans defining the actions to be taken in the event of the monitoring equipment failing should be established. These plans ensure the completeness of the stored test material

logistics

1- When a testing facility prepares sample kits or materials for sampling , the systems used to manufacture , distribute , sample and return these materials to the testing facility must be documented and the systems and procedures used must be validated.

2- Details of the logistics required for a particular study should be documented in the analysis plan or similar document approved by the sponsor and the analytical project leader.

3- The type of material required, the type and design of packaging, the timing and manner of distribution from the test facility to the investigator and vice versa, the controls and storage conditions carried out should be detailed in the documents listed above.

4- The procedures involved in the logistics should be subordinated to the quality control procedures to ensure in practice compliance with the specific requirements.

Carrying out the work

The requirements for working with computer systems, validation and processing of the test materials are described here.

General

  1. All analyzes or evaluations of samples should be performed according to the clinical protocol and the analytical plan. Consequently, it should be verified that the analytical plan does not contradict or exceed the requirements of the clinical trial protocol.
  2. All data generated during the implementation of the analytical phase should be documented directly, correctly, accurately and legibly. These entries should be dated and signed or paraphrased.
  3. Any changes to the data should be made so that the previous entries are not obscured. The reason for the changes should be recorded and traceable by the date and signature of the person who made the change.

Computerized systems

  1. Computer systems should meet the general requirements for equipment as described in the directive. Due to the nature of computerized systems and their key role in work processes, further requirements apply to their use. The computer systems should in all cases be appropriately validated and maintained and demonstrably serve the purpose.
  2. Computer systems used to receive, capture, process or document the raw data should be acquired, developed, tested, published, used and maintained in such a way that they comply with guidelines or laws. When a computer system is used to collect raw data, a definition of what the raw data represents should be documented. This is usually documented within the SOP for this system.
  3. Procedures to ensure the security and functionality of the computer systems should exist. These should include maintaining a data audit trail, the date and time, and the person responsible for data collection, system change control procedures, maintenance, and system backup procedures that ensure the integrity of the test data.
  4. Access to the computer systems should be restricted to authorized personnel.
  5. If the data is backed up electronically, methods should be in place to ensure that the data can be retrieved over and over again.

Validation of the methods

  1. The choice of platforms and analytical methods should take into account current regulatory standards and the sponsor's expectations.
  2. Any analytical method used in the analysis of test samples should be appropriately documented, validated, controlled and approved with recognized acceptance criteria. Changes to a method should be checked and validated, resulting in the output of another version of the method.
  3. Any analytical method should be adequately validated and demonstrated suitability for use.
  4. Reports showing the validity and sustainability of such methods within the experimental facility should be maintained.
  5. Analysis methods should not be changed during the conduct of a study without the prior consultation of the sponsor and its approval. Such changes should be controlled, documented and appropriately approved and may result in the need for further process validation.

Processing of test materials

  1. Trial materials should be analyzed and documented within a timeframe and in accordance with patient safety regulations and the trial protocol, analytical plan, SOPs, and any contractual requirements.

Repeat analysis

  1. The laboratory should have documented procedures that include rules for repeating analyzes in accordance with pharmaceutical industry standards.
  2. Specific rules covering the performance of repeat analyzes can be covered in the experimental protocol or in the analytical plan.

safety

  1. Laboratory procedures should take into account local legalization and standard practices regarding the safe handling of hazardous substances and test materials.

reporting

The reporting options and the content of the various reporting options are described here.

General

  1. It is acceptable to document analytical results in different ways. Examples of typical reporting mechanisms are: Analytical Reports: A formal report that can be issued after the work outlined in the Analytical Plan is complete. Analytical Results: A document containing only the results, which is usually issued quickly after the sample analysis is completed on a given day for a given topic.
  2. The analytical plan should include the type of reporting that was carried out and the schedule for securing these documents.
  3. The decision on the type of report should be agreed between the sponsor and the analytical project manager and, if necessary, the investigator.
  4. All reports should undergo a QC review to ensure the accuracy and validity of the information generated.
  5. Copies of the analytical report or results should be given to the sponsor and investigator.
  6. A copy of all analytical reports and analytical results issued should be retained by the testing facility.

Analytical report

  1. The Analytical Report should be dated and signed by the Analytical Project Manager to indicate acceptance of responsibility for the validity of the reported data.

Content of the analytical report

  1. An analytical report should include at least the following:

a) Identification of the analytical work by means of a descriptive title and an identification number

b) The clinical trial number

c) Name and address of the sponsor

d) Name and address of the investigator

e) Name and address of any testing facility and any testing facility involved that includes the identity of any investigator.

f) Name and address of the analytical project manager

g) Start and end dates of the laboratory work

h) A quality audit certificate

i) A description of the processes and materials used, including the data processing techniques and any statistical methods used

j) A presentation of the results

k) All information and data necessary for the analytical plan

l) The locations where the analytical plan, any samples that need to be retained, the data and the final analytical report will be kept.

  • Improvements or additions to a final, already published analytical report should be added in the form of an addition. Additions should clearly state the reasons for the improvements or additions and be approved by the dated signature of the Analytical Project Manager.

Analytical results

Analytical results should be recorded appropriately and accurately. Such reports should include at least the following:

a) Identification of the analytical work with a unique identification number

b) The clinical trial number

c) Identity of the sponsor

d) Identity of the test facility and the investigator to whom the results are to be forwarded

e) Name of the analytical project manager

f) Presentation of the results

  1. The analytical results should be issued with the dated signature of an authorized signatory
  2. Analytical results can be reissued if corrections or additions are required. In these circumstances, the corrected document must make it clear that the results will be changed and include the reason for any such changes.

Quality control

The laboratory should conduct appropriate QC procedures to ensure the quality and accuracy of all aspects of the work performed and reported.

QC procedures can apply but are not limited to the following aspects of the work:

  1. Within analytical batch acceptance criteria.
  2. Results of the external competence.
  3. Preparation of analytical plans and compliance with clinical protocol.

Experimental facilities should become members of external accreditation and performance schemes to demonstrate the competence of the work being done.

Quality audit

  1. An independent audit of the laboratory should be performed to ensure patient safety, patient confidentiality, data integrity, and GCP compliance. This includes confirmation that the clinical protocol , analytical plan, SOPs and this guideline are being followed.
  2. Facilities, systems, equipment, methods, quality control procedures, personnel, reports and documentation should be audited at regular intervals according to a specific program.
  3. Audits should be carried out by competent personnel appointed by the test facility management. These personnel should be independent of the work being audited. Independent audits by external experts can also be used.
  4. All audit results should be recorded. The reports of the tests should include all observations made during the test.
  5. Analytical project management and experimental facility management should respond to these audit reports in a timely manner.
  6. Any indicated corrective action should be followed up to ensure appropriate implementation.
  7. After the audit has been carried out satisfactorily, an audit certificate should be drawn up which confirms the activities tested and the correct implementation of the activities with the guideline.

Retention and archiving of reports

A laboratory will generate two types of records while performing an experiment: test records and laboratory records. Both types of records must be maintained and are necessary for the reconstruction of the work.

The following should be retained for the duration determined by appropriate authorities or as defined in the experimental protocol

a) The analytical plan, data, samples, analytical results and the final analytical report

b) Records of all audits carried out by the quality audit function

c) Records of the qualifications, training, experience and job description of the staff

d) Records and reports of equipment maintenance and calibration

e) Archive records of SOPs including the register and any operating instructions that are part of an SOP.

f) The records and reports of any quality control tests performed to confirm the accuracy of the work

  1. Samples should be retained as required by GCP, but only for as long as the quality of the samples allows evaluation.
  2. Experimental materials should be retained in such a way that their integrity and the accessibility of the retained material is ensured.
  3. If a testing facility does not have adequate facilities to store such materials, commercial archiving facilities should be used.
  4. If a research facility ceases operations and has no legal heir, the archived material should be transferred to an appropriate archive named by the sponsor of the study.

confidentiality

Procedures should ensure that a sponsor's proprietary information is not disclosed to anyone who is not an authorized person.

  1. Procedures for handling experimental materials, collecting data and reporting results should be designed to ensure the arrangements of confidentiality, coding and blinding of the study within the requirements of GCP, the Helsinki Declaration and the experimental protocol.
  2. The sponsor should be informed of any incident that might compromise the dazzling of the study, either by accident or as a result of an investigation.
  3. Procedures should ensure that the sponsor's self-information is not disclosed to anyone other than authorized personnel.

Aperture

The testing facility should have procedures in place to ensure the independence of the study.

The laboratory should be aware of all blinding and unblinding circumstances that apply to a study and should take care not to inadvertently unblind a study. 

Particular care should be taken in reporting results to ensure that unblinding does not occur.

Patient safety

The safety of study participants is above every other aspect of the study.

Individual evidence

  1. ↑ a b EMA, Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples (as of June 18, 2014) .
  2. ↑ M.McGraw, S.Shearn: Principles of good clinical practice . 1st edition. Pharmaceutical Press, London 2010, pp. 1-13 .
  3. ↑ a b c d e f g P. Carson, N. Dent: Good laboratory and clinical practices . Heinemann Newnes, Oxford 1990, ISBN 0-434-90281-0 .
  4. ^ Good Clinical Laboratory Practice (GCLP) . Research Quality Association, United Kingdoms 2012, p. 3 .
  5. ^ Good Clinical Laboratory Practice (GCLP) . Research Quality Association, United Kingdoms 2012, p. 4 .
  6. ^ J Seiler: Good Laboratory Practice: The Why and the How . 2nd Edition. Springer Berlin Heidelberg, Berlin, Heidelberg 2012, p. 15-18 .
  7. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 5-8 .
  8. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 9 .
  9. ^ Good Clinical Laboratory Practice (GCLP). Pp. 11–12 , accessed on December 31, 2016 (English).
  10. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 12-13 .
  11. ↑ World Health Organization: Good clinical laboratory practice (GCLP). 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 13-14 .
  12. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 15 .
  13. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 16-17 .
  14. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 18-20 .
  15. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 21-22 .
  16. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 23 .
  17. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 24 .
  18. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 25-26 .
  19. ↑ World Health Organization: Good clinical laboratory practice (GCLP) . 1st edition. Geneva, Switzerland 2009, ISBN 978-92-4159785-2 , pp. 27 .
  20. ↑ a b Research Quality Association (Ed.): Good clinical laboratory practice (GCLP) . 1st edition. Suffolk 2012, ISBN 978-1-904610-21-2 , pp. 28 .

literature

  • World Health Organization : Good Clinical Laboratory Practice (GCLP). World Health Organization, Geneva 2009, ISBN 978-92-4-159785-2 .
  • W.Stevens (2003): Good Clinical Laboratory Practice (GCLP). The need for a hybrid of Good Laboratory Practice and Good Clinical Practice guidelines / standards for medical testing laboratories conducting clinical trials in developing countries. In: Quality Assurance. Vol. 10, No. 2, April / June 2003, ISSN  1052-9411 , pp. 83-89.
  • European Medicines Agency : Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples. European Medicines Agency, February 28, 2012, EMA / INS / GCP / 532137/2010.

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