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6. Good laboratory practice

6. Good laboratory practice

6.1 Introduction


Both the AMC and the VUmc aim to carry out basic and translational research of the highest quality. The regulations described here are intended to improve the reliability and reproducibility of basic and translational biomedical research, and to prevent scientific misconduct.

6.2 Good laboratory practice


Basic and translation biomedical research is performed in dedicated laboratories following strict rules, regulations and laws. In addition:

  • The research performed should be of a high standard and quality, should be ethical, and should respect laboratory animals, healthy volunteers and patients.
  • The personnel should be knowledgeable and well trained.
  • The laboratories should be well equipped and the apparatuses should be maintained properly.
  • Procedures should be well described, validated and up to date.
  • Findings should be recorded properly in a laboratory notebook.

Scientific research is performed in the framework of projects that should contain a transparent formulation of the aim of the research, following a critical analysis of the literature and any other relevant data. The principal investigators are responsible for the quality, accuracy, traceability and reproducibility of all research findings obtained within their research projects.

Many different diagnostic laboratories at both the AMC and the VUmc have adopted quality control systems and are accredited according to, for example, CCKL or ISO 15189 standards. Although it is not mandatory for basic and translation biomedical research laboratories to comply with these CCKL standards and obtain accreditation, it is very useful to organize the research according to those rules and regulations. Imposing these rules and regulations in the laboratory facilitates patent applications and increases funding opportunities from national and international foundations and consortia, and from biopharmaceutical companies.

 Strict rules for basic and translational research have been laid down in specific acts. These comprise, for example, strict rules for the use of radioactive material and genetically modified organisms, and the handling and use of laboratory animals.

Radioactive material, see: www.agentschapnl.nl
Genetically modified organisms, see: www.rivm.nl
Laboratory animals, see: www.minvws.nl
General information on applicable laws and government acts, see: www.rijksoverheid.nl

6.3 Project administration


In order to keep track of the research performed, biomedical research laboratories should maintain a proper project administration. The project administration must include at least the following items.

  1. 1. An overview of all current and past projects.
  2. An identification tag (e.g. a project number).
  3. A record of changes that have been made since the project was granted/started.
  4. The name and function of the principal investigator and scientific and other personnel involved in the project.
  5. Expected start and end dates of the project.
  6. Information on parts of the research that will be outsourced.
  7. Information about materials to be stored for prolonged periods of time.
  8. Information on the validation of apparatuses and processes.
  9. Justification of research processes.
  10. Information on handing materials and unpublished data to third parties.
  11. Quality control.
  12. Mid-term and end report to the financing parties, foundations, consortia and/or industries.
  13. Information on co-authorships of publications resulting from the research.
  14. Ownership of findings, patent filing.

The CCKL rules and regulations can serve as a guideline for proper project administration.

6.4 Keeping a laboratory notebook

  • A laboratory notebook is primarily kept to record all the steps taken during experimental procedures.
  • Keeping a good laboratory notebook prevents loss of data, enables easy continuation of the research when laboratory staff leave, and prevents misinterpretation of data and possible fraud.
  • A laboratory notebook should have a permanent binding; loose-leaf, spiral-bound or other temporary binding systems are not recommended.
  • The laboratory notebook should contain an index, and the pages should be numbered and dated.
  • Paper and (permanent) ink should be of sufficient quality.
  • The entries in the laboratory notebook should be legible and complete.
  • Procedures must be described in full detail (or reference must be made to standard operating procedures), including the equipment that is used.
  • Printouts and photographs should be glued (not stapled) inside the notebook.
  • All results, observations and detailed calculations should be written down.
  • Any subsequent data added to the notebook should be entered on a separate page with reference to the original entry.
  • The principal investigator is responsible for the quality of the laboratory notebook and should check it on a regular basis.
  • Old laboratory notebooks should be stored in a safe place at the institute where the research was conducted, and should be kept for 10 years after the last publication derived from the results indicated in the laboratory notebook.

Alternatively, electronic laboratory management systems may be used. For such an approach, do not use computer programs, like Word and Excel, which allow entries and dates to be altered without traceability. For information about electronic laboratory notebooks (ELNs), see for example:
http://www.labarchives.com/index.php
http://download.cnet.com/iPad-ELN/3000-2654_4-10901569.html
http://www.cambridgesoft.com/

6.5 Standard operating procedures

 
In addition to keeping a laboratory notebook in which all protocols are written down, it is recommended to keep a database of/binder containing all standard operating procedures (SOPs) that are followed in the laboratory. A SOP is defined as a 'detailed, written instruction to achieve uniformity of the performance of a specific function'. In basic and translational research, this often refers to a detailed protocol on how to perform a specific experiment. A SOP should address the following items:

1. Aim
2. Application
3. Definitions
4. Principle of the test
5. Safety
6. Reagents and solutions
7. Equipment
8. Samples
9. Standard procedures
10. Results
11. Report
12. Quality control (procedure/samples)
13. Disposal of chemicals and samples
14. Additional documentation
15. Remarks
16. Literature references
17. Appendices.

All SOPs should be numbered and stored both in a central place (or on a website) and in the laboratory. SOPs should be approved by the principal investigator and receive regular updates.

6.6 Accreditation of laboratories


Some 20 years ago, clinical laboratories began setting up an accreditation system to guarantee and demonstrate the quality of their processes and the results of their tests. The Foundation for the Promotion of the Quality of Laboratory Work and the Accreditation of Laboratories in the Health Service (Coördinatie Commissie ter bevordering van de Kwaliteitsbeheersing op het gebied van Laboratoriumonderzoek in de Gezondheidszorg; CCKL) was initiated for this purpose. The CCKL rules require the implemented quality system to be laid down in a manual that briefly sets out the laboratory's activities and organization, procurement of resources, quality of the facilities, initial and subsequent training of staff, servicing and calibration of apparatus and equipment, and how results are reported. All this has to comply with ISO 15189, an international standard for laboratories. The CCKL explains how this applies to Dutch laboratories in its Practice Guide (Praktijkrichtlijn ).

Even though accreditation is an option for both translational and basic science laboratories, the guidelines and rules can be a great aid when organizing your research efforts.

For more information: www.cckl.nl

6.7 Examples of laboratory notebook guidelines


The following examples are taken from www.bookfactory.com and www.vwr.com .

Introduction
Recording ideas, inventions, experimentation records, observations and all work details in a notebook is a vital part of any laboratory process. Careful attention to how you keep your notebook can have a positive impact on the patent outcome of a pending discovery or invention.

The following are some general recommendations to help you keep more efficient and accurate notebook entries. Remember, however, that these are simply a suggested set of guidelines. Only your attorney can supply the exact guidelines you should follow in order to satisfy specific legal requirements. That is why we recommend that you consult your legal counsel.

Recording data
Your notebook is a vital record of your work whether it is for patent purposes, legal records or documenting drug research under FDA guidelines. The notebook can help you prove:

a. Exact details and dates of conception
b. Details and dates of reduction to practice
c. Diligence in reducing your invention to practice
d. Details regarding the structure and operation of your invention
e. Experimentation observations and results
f. A chronological record of your work
g. Other work details.

Follow a few simple rules of thumb

  1. Always record entries legibly, neatly and in permanent ink.
  2. Immediately enter into your notebook and date all original concepts, data and observations, using separate headings to differentiate each one.
  3. Record all concepts, results, references and other information in a systematic and orderly manner. Language, charts and numbering systems should be maintained consistently throughout.
  4. It is acceptable to make your entries brief. Always, however, include enough details for someone else to successfully duplicate the work you have recorded.
  5. Label all figures and calculations.
  6. Never, under any circumstances, remove pages from your notebook.

Remember to treat your notebook as a legal document : it records the chronological history of your activities. The following guidelines should help you maintain the consistent and accurate entries needed for future legal purposes.

  1. Start entries at the top of the first page, and always make successive, dated entries, working your way to the bottom of the last page.
  2. After completing a page, sign it before continuing to the next page.
  3. Make sure that you record the date of each entry clearly and unambiguously.
  4. Never let anyone other than yourself write in your notebook (excluding witness signatures, which are discussed later).
  5. Never leave blank spaces, and never erase or remove material you have added. Simply draw lines through any blank spaces while you are making your entries.
  6. Do not erase errors. Just draw a single line through any erroneous entry, and then add your initials. Enter the correct entry nearby.
  7. You can supplement your entries with supporting material (e.g. test result printouts and other documentation). But you must permanently affix the material onto a page in its proper chronological location.
  8. Never rely solely on any supplemental attachment. Always include your own entry describing the attachment and add any conclusions that you might draw from its substance.
  9. Occasionally, secondary sources might be too large or inappropriate to attach directly to your notebook. In this case, you can add all secondary sources to an ancillary record maintained precisely for this purpose. However, always remember to write a description of these secondary sources, clearly and unambiguously, in your notebook.

Documenting patent activities
A primary purpose of a notebook is to document work that may be patentable. To support patent activities, it is necessary to provide clear, concise, chronological entries with specific dates. To rely on these dates, you must have at least one non-inventor corroborate that the events actually happened and that he/she understood your invention by signing and dating the 'Disclosed to and understood by' signature blocks.

Your notebook should help you document and prove:

  1. Conception date - the date that you knew your invention would solve the problem.
  2. Date of reduction to practice - the moment that you made a working embodiment of your invention.
  3. Diligence in reducing your invention to practice - diligence refers to your intent and conscious effort to make a working embodiment. You are not required to rush, or even to take the most efficient development strategy. But your notebook must include details relating to your diligent activities. These are dates and facts that show the activities that you have conducted to reduce the invention to practice, and when such activities were conducted. Since you may still be diligent despite periods of not working on reducing your invention to practice, always remember to provide reasonable explanations for these periods of inactivity by supplying facts relating to why there was no activity during the period in question. (e.g. unavailability of test conditions or equipment).
  4. How to make and use your invention - provide sufficient details to teach a colleague how to make and use your invention.
  5. The best mode of practicing your invention - document the best way to practice your invention.

A non-inventor colleague should corroborate each of these events/facts by signing the 'Disclosed to and understood by' blocks on the relevant pages.

For more information: www.cckl.nl

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