Annex

1 SOP

1.1 General Recommendations

This part of the attachment outlines in detail the content a standard operating procedure (SOP). All SOPs should have the same structure and section titles. The actual content of each section is described in the following sections (9.1.2. Structure and Content of SOP). There might be parts of a procedure, which are not covered by the given sections of the document template. Hence additional section and titles can be added to the current document structure. But one should avoid deleting any sections and their titles.

The drafting of SOPs starts after the initial development phase of a method. The main objectives of SOPs are:

  • Document the way an operational procedure has to be executed (Operational Procedure).
  • Execution of a procedure in an exactly repeatable and hence reproducible way over time and space. (Standardized Operation).
  • SOPs permit the determination of performance characteristics of the operational procedure and with it the specification of acceptance criteria.

The drafting process is facilitated, if the content of each of the section is already available. The content of SOPs should be structured in such a way that it focuses on usability. The comprehensibility of the document is essential, so that any other laboratory can easily implement the procedure in their own laboratory without any further in-depth training. Each section should have an appropriate level of details.

SOPs shall be kept under version control. Any refinement of the content and with-it of the text of a SOP should lead to a new version number. All results of a measurement shall be assigned to the respective version number of the respective SOP.

1.2  Structure and Content of SOPs

The structure of the sections (chapter titles) of SOPs are listed and their aim and content are outlined below.

1.2.1 Chapter Titles of SOPs

  1. Introduction
  2. Principle of the Method
  3. Applicability and Limitations (Scope)
  4. Related Documents
  5. Equipment and Reagents
    1. Equipment
    2. Reagents
    3. Reagent Preparation
    4. Reference Materials
  6. Procedure
    1. Flow Chart of the Measurement Procedure
    2. Step by Step Description of the Measurement Procedure
    3. Definition and Equation of the Measurand
    4. Statistical Data Evaluation
    5. Reporting of the Results
  7. Potential Pitfalls
  8. Controls, Quality Control Samples and Acceptance Criteria
  9. Health and Safety Warnings, Cautions and Waste Treatment
  10. Abbreviations
  11. References
  12. Annex

1.2.2 Content of the different sections of SOPs

In general, all SOPs follow similar ideas or outlines, but there might be some differences in the detail structure. Therefore, a description of the content of each section is given below. If there is any section of your measurement procedure missing in the document template, then it should be added at the appropriate location. No section of the template shall be deleted.

1.2.2.1 Introduction

The introduction of the SOPs describes shortly its content and aim supporting the user in selection the appropriate measurement procedure.

1.2.2.2 Principle of the Method

This section provides a description of the biological or analytical chemical principles, which build the basic of the measurement procedure. It should help the users in their understanding of the method.

1.2.2.3 Applicability and Limitations (Scope)

The scope describes the boundaries, within which the measurement procedure of the SOP can safely be applied. For example, the scope describes the materials, for which the measurement procedure is fit for purpose.

It is essential to have the comprehensive understanding, for which area of application the measurement procedure has been tested and hence the measurement model is valid. An appropriated description of the scope of the measurement procedure helps users comprehending under which condition the application of the method is fit for purpose or not.

1.2.2.4 Related Documents

This section lists all the SOPs, which are related to this SOP and which have to be in place so that the actual measurement procedure functioning properly.

1.2.2.5 Equipment and Reagents

1.2.2.5.1 Equipment

A comprehensive list of all the equipment, which is used to perform the measurement procedure described in the SOP.

1.2.2.5.2 Reagents

A comprehensive list of all the reagents and chemicals, which are used to conduct the measurement procedure. If feasible specify all chemicals using their CAS number.

1.2.2.5.3 Reagent Preparation

A step by step description, how the different reagents are prepared, which are used in the measurement procedure. This does not include ready to use reagents bought from manufacturers.

1.2.2.5.4 Reference Materials

All measurements are relative measurements, which are directly linked to reference materials. Here all the used reference materials and their detailed specifications are given. Such information is specified in the reference material certificates, which should also provide information about the traceability of the certified values.

1.2.2.6 Procedure

1.2.2.6.1 Flow Chart of the Measurement Procedure

It proved very useful in many fields of measurement science to have a detailed flow chart of the measurement procedure. This allows obtaining an overview of the measurement procedure or locating a single step within the whole context of the procedure. Therefore, a detailed flowchart is drawn for each logical unit of steps, which is listed in the written description of a measurement procedure.

Figure: the flow chart of the MTS viability assay1 is given as an example –
 The flow chart shows each logical unit of steps of the measurement procedure

1.2.2.6.2 Step by Step Description of the Measurement Procedure

A detailed step by step description of the measurement procedure is one of the essential parts of any SOP. This description has to be in such detail that any person familiar with the measurement method and its field can directly perform the measurement without any additional training of information. It should include all the special aspects of the measurement procedure.

This detailed description is the essential precondition so that each measurement can be performed exactly according to the SOP.

1.2.2.6.3 Definition and Equation of the Measurand

The measurand2 describes the value of the quantity, which is intended to be measured with the measurement procedure detailed in the SOP. The comprehensive understanding of the specification of the measurand is essential for all measurement procedures. The definition of the measurand includes the detailed equation of the measurand2,3. It shall list all the parameters of the equation and it describes the measurement model.

1.2.2.6.4 Statistical Data Evaluation

The section describes step by step the statistical evaluation of the measured values.

1.2.2.6.5 Reporting of the Results

The reporting of the measurement results is outlined in this section.

1.2.2.7 Potential pitfalls

A listing of potential pitfalls helps users of the SOPs to debug any measurements, which do not pass the acceptance criteria, which show out of specification control results or which results of the quality control samples are not within the range of the control chartings. This section helps the users avoiding the reporting of blunders.

1.2.2.8 Controls, Quality Control Samples and Acceptance Criteria

Controls, quality control samples and acceptance criteria allow to establish the confidence that the results obtained with the measurement procedure specified in the SOPs can be trusted. They are essential quality control measures, which should confirm that the performed measurements are according the specification of the measurement procedure and the measurement model is valid. Controls, quality control samples and acceptance criteria should be designed in such a way that they detect any shortcomings, mishap or failures when performing the measurements. Their design shows the standardization bodies that the context of the measurement procedure is understood and the robustness of the method has been established thoroughly. Their effectiveness persuades the regulatory bodies of the quality of the measurement procedure.

1.2.2.9 Health and Safety Warnings, Cautions and Waste Treatment

All health and safety warnings together with all precaution measured are outlined in this section. They help the user to perform measurement procedure safely and avoid any health risk. It also tells the users, if they fulfill all the training requirements to handle potentially dangerous goods. In addition, the waste treatment of any hazardous reagents used in the measurement procedure is described in detail. Waste treatment has to comply with international regulation.

1.2.2.10 Abbreviations

All abbreviations are defined in this section.

1.2.2.11 References

This section lists all references, which are essential for the SOPs. The listing should include any publication of regulatory bodies or of standardization bodies, which are relevant for the SOP.

1.2.2.12 Annex

This section lists any annex, which are essential for the implementation of the SOP.

 

1.3 Checklist

The checklist helps to review the completeness of the SOP.

Structure of SOP

  1. Section of SOP in right order
  2. Are there missing sections
  3. Are there any additional sections

Equipment and reagents

  1. Is the list of equipment comprehensive and specified in enough detail?
  2. Is the list of reagents itemizing all reagents used in the SOP?
  3. Are all the reagents specified well enough, so that any confusion can be exclude (CAS #)
  4. Is the preparation of the reagents described detailed enough?

Reference material

  1. Exact specifications of the reference material given
  2. Conditions to store the reference material are described
  3. Rules to check the stability of the reference material given

Understanding of measurement procedure

  1. Scope of the measurement procedure clearly defined
  2. Detailed flowchart of measurement procedure is included
  3. Comprehensive step by step description of the measurement procedure existing
  4. Is the level of detail sufficient, so that the description of each step leaves no room for interpretation?
  5. Measurand clearly defined
  6. Full equation of the measurand included
  7. All parameters of the equation of the measurement defined
  8. List with potential pitfalls existing
  9. Full set of controls, quality control samples and acceptance criteria with a description, of which part of the measurement procedure is monitored, given
  10. Are the acceptance criteria in line with relevant publications and requirements of the regulatory bodies?

Statistical evaluation of the measurement

  1. A full description of the statistical evaluation of the measurement given
  2. A data set to testing the proper functioning of the statistical evaluation given
  3. Simple rules to verify the approximate values of the results independently given

Quality control samples

  1. Exact specifications of the quality control samples given
  2. Conditions to store the quality control samples are given
  3. Rules to check the stability of the quality control samples given

1.4 References

  1. Roesslein, M. et al. Use of Cause-and-Effect Analysis to Design a High-Quality Nanocytotoxicology Assay. Chem. Res. Toxicol. (2015). doi:10.1021/tx500327y
  2. BIPM. International vocabulary of metrology - Basic and general concepts and associated terms (VIPM). JCGM 200:2012 1–108 (2012) https://www.bipm.org/en/publications/guides/vim.html
  3. BIPM - Joint Committee for Guides in Metrology (JCGM). Evaluation of measurement data - Guide to the expression of uncertainty in measurement. JCGM 100:2008 1–134 (2008) https://www.bipm.org/en/publications/guides/gum.html