Originally Published MDDI January 2005
Laboratory notebooks can be an integral part of a company's controlled documentation but must be managed carefully to ensure quality.
John A. DeLucia
|Manufacturers must consider many factors during a product's |
development to ensure proper end-use of the device.
Controlled documentation is a vital component of a quality system. Its benefits include information availability, knowledge preservation, and controlled review and approval of revisions and obsolete documents. Typically, controlled documents may include work instructions, procedures, policies, product drawings, and specifications. Laboratory notebooks are sometimes neglected; but their information can be used in the documentation required in FDA-regulated industries.
Laboratory notebooks can be a primary source for documenting raw data generation for the test engineer and laboratory technician. The notebooks also are used for recording patented inventions and concepts. Laboratory data not otherwise controlled by standard operating procedures or test forms also can be recorded in the notebooks. Such data include, but are not limited to, laboratory data resulting from product development, failure investigations, complaint investigations, product validations, or competitive product testing to support marketing claims. Any individual in a company who is required to gather data could use a laboratory notebook successfully. However, generally, individuals who use laboratory notebooks are from research and development, quality engineering, manufacturing engineering, and testing laboratories departments.
Good laboratory notebook practice is just one way to comply with the much larger concept of good laboratory practice. FDA promulgated the good laboratory practice (GLP) regulations, 21 CFR Part 58, on December 22, 1978. The regulations became effective in June 1979 and established standards for the conduct and reporting of nonclinical laboratory studies. The regulations are intended to ensure the quality and integrity of safety data submitted to FDA.1 GLP addresses the documentation of research. It provides a means of ensuring that all work is done according to agreed procedures and that the data are properly recorded. The recommendations in this article are designed to help companies develop procedures for good laboratory notebook practice. Moreover, these recommendations can be adapted to develop a procedure for a particular company.
A laboratory notebook is a permanently bound, rigidly constructed book that can protect its contents in a laboratory environment. Typically, notebooks are issued by the document control department and are tracked and controlled by a serial number. When issued to laboratory workers, the serial number is entered on the cover of each notebook along with the recipient's name and the date the notebook was issued. The serial number should also be noted in a log maintained by the document control department. Once issued, the user should write his or her name and the title of project or purpose of the notebook on the front page.
The notebook should also contain a table of contents that includes a listing, by page number, of all experiments or entries. A space should be provided where report titles or numbers can be entered. On each page, the user should state the report title and project number, laboratory notebook number, and page number. Each page should have a space for a “performed by” signature and date. If the page describes a potential patented product or process, the inventor should sign an “invented by” signature space. A “witnessed by” or “reviewed by” signature and date also should be required on each page. A witness is defined as a member of the organization who can objectively review the information, but who is neither a coinventor nor integrally involved in data collection. Notebooks are available that have a preprinted table of contents, report description, page entry, and signature lines.
Various data entries may be made in a laboratory notebook. The more prevalent practice uses the laboratory notebook to document an experiment and collect test data. So it is worthwhile to look at the proper documentation practices involved in this activity.
Before recording any data, a standardized format should be used to make entries. The list below outlines the information that should be included.
Purpose and Objectives. The purpose and objectives section should include a statement about or definition of the experiment. This section identifies anticipated outcomes and provides an action plan to achieve the outcomes.
Test Articles. A description of all test articles must be written in the laboratory notebook. It is important to provide the test-sample lot numbers and reference any documents that contain the complete history or traceability of the test articles. For instance, if the protocol assesses a newly designed component, minimum information would include the component specification number, revision level, supplier, lot or control number, purchase order number, supplier shop order record, and a copy of the certificate of compliance. All test samples should be retained until after the work has been witnessed in the notebook. If the test samples are to be archived, the archive location should be indicated in the laboratory notebook.
Test Preparation. The test preparation section is where the relevant test methods, equipment, and conditions must be described. All laboratory equipment must be identified by type, manufacturer, and model or tool number. It is important to verify that the calibration and preventive maintenance are current on all equipment.
All test methods and test specifications must be described in detail. This can be done by referencing previously approved and issued documents (including revision levels) or by referencing previous laboratory notebook entries by notebook number and page. Environmental conditions, which may be important and relevant to a test, should be noted. It is important to describe all conditions relevant during testing, such as room temperature, humidity, or sample conditioning. All monitoring equipment used to collect environmental data must be identified in the same way. Laboratory equipment used in the study must also be included.
Test Results. Minimum requirements for collecting test information include entering test results with units. All data transformations, calculations, or operations performed on the data need to be described. Statistical analysis of the data should be carried out according to the prospective protocol instructions and recorded in the notebook before performing the analyses on the data set. A summary of the test results with conclusions should be included in this section. If inconsistent results or unusual data points were encountered, then these must be identified and explained. Lastly, study initiation and completion dates also should be documented.
Maintenance of Data Integrity. Maintaining data integrity is critical to good laboratory notebook practice. It is important to write legibly and clearly and to use recognizable and accepted terms. If abbreviations, code names, trademarks, trade names, or numbers are used, they should be defined at least once, at first use, in every notebook. As with any quality record, errors should be deleted by drawing a single line through the error that does not render the deletion illegible. A notation stating the reason for the deletion should be added, initialed, and dated by the person who made the deletion. Pages should never be removed from a laboratory notebook.
All data must be entered directly into the notebook, rather than on separate papers for later copying into the notebook. When attaching forms, photographs, charts, statistical printouts, etc., using glue or tape ensures permanence. A mark or signature should be placed across any portion of the attachment and lab notebook page. There must be no document replacement after the witness signs. If there is blank space at the bottom of the page, lines drawn across the length and width prevent additional comments or results from being added after the page is witnessed. All transcribed data must be signed and dated by the individual performing the transcription. The location of the raw data should also be included if it is not in the notebook.
Control of Laboratory Notebooks
The document control department is responsible for the issuance, retrieval, and maintenance of laboratory notebooks. However, during use, the assigned individual assumes responsibility for the care and whereabouts of the book at all times. The control of laboratory notebooks should be no different from other controlled documents or quality records.
The laboratory notebook should be returned to the document control department when completed or upon termination of its use. Before a laboratory notebook is returned, appropriate personnel should review it to ensure that all items were entered in accordance with procedure. The document control department should note the return date in its log. All returned laboratory notebooks should be filed in a centralized holding area in the department and should not leave the area unless they are signed out. If a laboratory notebook is lost, the document control department should be notified in writing, detailing the circumstances surrounding the loss. This notice must be signed and dated by the employee and his or her immediate supervisor.
Lastly, laboratory notebooks should be retained like any other controlled document. Their retention should be specified in the company's records retention procedures.
Laboratory notebooks are an important component of a company's quality system and controlled documentation. The notebooks play an important role in preserving and transferring valuable information and knowledge within a company.
An employee's laboratory notebook is subject to inspection by colleagues, supervisors, or outside regulatory body auditors. Thus, it is imperative that GLP notebook practices are implemented and that a standardized procedure is in place for handling laboratory notebooks. Laboratory notebooks must contain all of the pertinent information required by the company. They must also be maintained in a controlled manner. Defining these requirements ensures that the contents of laboratory notebooks can withstand any challenges to their validity, accuracy, or legibility.
1. FDA Compliance Program Guidance Manual, Program 7348.808, Chapter 28, “Bioresearch Monitoring: Good Laboratory Practice (Nonclinical Laboratories),” February 21, 2001.
John A. DeLucia is vice president of regulatory affairs and quality assurance at Smiths Medical ASD Inc. (Keene, NH).
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