Documentation laboratory notebook

Laboratory notebooks—It may be debatable to consider laboratory notebooks as text documents, but they should be mentioned here because of their importance in preclinical development. Laboratory notebooks are used to record experimental procedures, observations, raw data, and other important information. Although laboratory notebooks are rarely used for submission to regulatory agencies directly, they are available for inspection by the authorities in the Preapproval Inspection (PAI) and other GMP/GLP-related inspections. Currently, most of the major pharmaceutical companies still use paper-based laboratory notebooks. Electronic-based notebook systems are being developed and commercialized, which are discussed in Chapter 9. 

Forensic analysis is usually required for the collection of data in the course of determining whether legislation has been infringed. The customer requires that, above all, there is an unbroken chain of evidence from the time the samples were taken to the presentation of evidence in courts of law. In the laboratory this will include documentation and authorization for sample receipt, sample transfer, sub-sampling, laboratory notebooks, analytical procedures, calculations and observations, witness statements and sample disposal. All of these aspects can be called as evidence in court. 

FIGURE 10 Part of the MS Word template form to document the calibration of the autosampler. A 4-page template was used to document the results obtained for HPLC calibration so any laboratory notebook entries are not needed. Reprinted with permission from Reference 6. 

Although every experimentalist develops her/his own habits for recording research observations, maintenance of adequate and timely documentation is still insufficiently stressed. Exceptions to this statement may be cited, especially in industry where laboratory notebooks are read and endorsed on a regular schedule for proprietary motives. Next to the writing of monthly or quarterly progress reports, nothing seems at first glance more inef-... 

Tests to establish the identity, strength, and purity of the test and control articles need not comply strictly with GLP requirements (e.g., protocol, QAU inspection requirements), but good documentation of anal5dical test results (usually in a laboratory notebook) and retention of raw data for such tests is a good practice. As the development process proceeds and the same material is used in both nonclinical and clinical studies, CGMP principles wiU apply to the production and characterization processes. 

Enter all your observations of the experimental work and conclusions in a laboratory notebook that is a document reflecting all your work. Write your surname, initials, class number and the name of the course on the cover or first page of the notebook. Make all entries only in ink, concisely, accurately, and legibly, directly after performing an experiment. The writeup must contain the following information ... 

Documentation requirements are predicated on the types of batches to be manufactured at the pilot facility. For the development of novel formulations, laboratory notebooks are the primary source of documentation. Room and equipment logbooks should be maintained. Personnel training records and SOPs must also be maintained. Once the facility is used for the larger-scale batches described earlier, what was recommended now becomes required. Manufacturing runs need to be documented accurately, preferably in batch records. Logbooks should maintain an accurate record of the product history in rooms and equipment. At this level of manufacturing, it is also important that personnel training records be kept. These... 

In both academia and industry, the laboratory notebook is a legal document that records the work done by an individual researcher. Even in the USPTO s own view, its Disclosure Document Program does not diminish the value of the conventional, witnessed, permanently bound, and page-numbered laboratory notebook or notarized records [6]. Without a doubt, any experimental work might be worthless unless it is properly recorded for later use. Evidence of the dates of conception and reduction to practice of an invention may be established by a well-maintained laboratory notebook. Therefore, researchers should become familiar with how to keep persuasive laboratory notebooks. Of course, no notebook is ever perfect. However, the closer one comes to this objective, the better it will be. 

Data transformation steps should be documented in laboratory notebooks. 

The current good manufacturing practices (GMP) state that Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards [5]. This includes all electronic and hard copies of raw data, laboratory notebooks, and/or worksheets and reports. Additionally, the regulations require that records shall be readily available for authorized inspection [6]. Consequently, the organization must have a well-defined audit trail for the generation, storage, and retrieval of reports and raw data. It must also be shown that there is adequate document management and security of all raw data and reports in terms of both disaster recovery and prevention of falsification of results. 

In many cases method development chemists hold advanced degrees and possess years of laboratory experience. Their cGMP training is often limited, however, and thus inadequate for performing validation. The training program, therefore, must emphasize regulatory compliance, especially in notebook documentation skills. 

Conventional method development records are typically not the subjects of regulatory review. Failures, which are commonplace in early method development, are rarely investigated or fully explained. Laboratories that plan to use development data in a validation must document their data in accordance with regulatory standards. Therefore, all entries must be recorded in laboratory notebooks that shall be readily available for authorized inspection [6]. 

Preventative Action. This observation could have been avoided by developing a laboratory SOP that describes proper documentation for all analyses conducted, including stability. Additionally, QA within the lab should have provided adequate oversight and monitoring of stability data generated by individual analysts through periodic reviews of laboratory notebooks. 

At this early stage, the batch record is frequently a simple set of instructions with wide parameters or no parameters at all. Batch records can vary between data recorded in laboratory notebooks to formal, typed documents. Regardless of format, data should be collected in these batch records at processing stages that could readily impact the production of the product. This data can then be utilized to assist in scale-up activities. 

Some authorities will insist on inspecting the documentation trail for process development, including laboratory notebooks. 

A second exception in the USA which influences the effective priority date of an invention (but not the official priority of the patent ) is the so-called swearing-back according to the Code of Federal Regulations, Title 37 (37 CFR, 1.131). If there is an interference with other patents or patent applications, the US patent authority will ask the applicant of USA-derived inventions to provide detailed information on the actual time of conception of the invention, reduction to practice and on all further steps which finally led to the current application. Proof of those activities can be provided by laboratory notebooks and other relevant documents, e.g. those which prove the involvement of a patent attorney during the process of drafting and filing the application in question. This information will be considered in order to assess the effective time when the invention was made and when it was reduced to practice in order to fulfil the requirements for patentability. 

Log books, laboratory notebooks (when used), batch production and control records, qualification and validation protocols and reports, investigations of deviations and failures, and other GMP documentation must be carefully identified, controlled, and archived in a manner that will facilitate its prompt retrieval. 

Laboratory records are kept very carefully in order to follow the progress of any study and to be able to repeat any steps that are necessary. Detailed records include all the information about samples, preparation methods, analysis results, and storage. These records provide the documentation necessary to prove that the research was done and how it was completed. All of this information together is data and there are two major places these data are kept a notebook and computer database. The Laboratory Notebook is an essential part of lab activities and the first record of all information. A laboratory notebook is needed to explain lab procediues, write down all lab data, show how calculations are made, and discuss the results of an experiment. A record of lab work is an important document, which will show the quantity and quality of the lab work that you have done. The laboratory database is the digital archive of information from the activities, experiments, and measurements of the laboratory. 

SCIENTIFIC DOCUMENTATION — ELECTRONIC LABORATORY NOTEBOOKS (ELNs)... 

But what does appropriate mean for scientific documentation Obviously, simple documentation is not enough there are additional requirements for a scientific notebook. Some companies sell preprinted paper notebooks, usually containing 100 to 150 pages, square grid or horizontal ruled, serially numbered in the upper outside corner, and bound at the left margin. Loose-leaf or spiral notebooks are not acceptable, because pages can be intentionally inserted or removed or accidentally ripped out. Any such action opens up the possibility that someone will question the authenticity of the data. Here is a summary of the most important laboratory notebook rules ... 

In the ELN, the electronic scientific document serves the role of a conventional laboratory paper notebook It is a container for laboratory data bound by regulatory guidelines. As an electronic regulatory vehicle, the electronic scientific document must meet GxP and 21 CFR Part 11 requirements mentioned earlier as well as the requirements governing paper laboratory notebooks. As a result, it must do the following ... 

In the ideal case, a section will disappear if it is deleted or if a new version is created. However, a page cannot be removed or content erased beyond recognition in paper laboratory notebooks. Consequently, the electronic scientific document should provide a special view showing all versions of sections as well as the deleted ones. In this view, the status of a section has to be clearly indicated. 

The inbox concept is particularly interesting for documentation systems, like ELNs. According to paper laboratory notebook rules, a scientist is not permitted to write to another notebook besides his own. The same applies to ELN software An external system like an agent will not be able to insert data into an electronic scientific document without user interaction. The inbox plays here the role of a database cache in between an external system and the secured notebook database. The scientist can take a look at the inbox items and can decide which item he wants to insert into his document. 

Electronic Laboratory Notebook (ELN) is a laboratory software for authoring, managing, and sharing electronic information for the purpose of scientific documentation. 

Electronic Scientific Document is a concept of ELN software that serves the role of a container for documented laboratory data underlying the regulatory guidelines for paper laboratory notebooks. 

Scientific Workspaces are a specialized concept of electronic laboratory notebook software underlying less restrictive regulations than electronic scientific documents. They are containers designed for personal preparation of data as well as for effective organization, sharing, and publishing of information within a team. 

Cycle Development does not have to be performed per a written procedure however, the procedure and results of all work must be recorded in laboratory notebooks, performed in accordance with cGMP documentation practices and sound scientific methods, and retained as part of the Validation Package. At the completion of Cycle Development work, a brief Cycle Development Report will be prepared that identifies parameters having a high probability of successfully meeting the Performance Qualification requirements. 

As product development can take several years to complete, it is important to have an effective document management system in place to record the work. The primary reference source for recording experimental work will usually be a laboratory notebook. The work should be checked, dated and counter-signed to satisfy GLP and intellectual property requirements. Experimental protocols are sometimes useful for defining programmes of work,... 

The conference report from the Crystal City III Workshop outlines the documentation requirements in detail [10]. The degree of documentation should be sufficient to recreate the validation. Prior to initiating a prestudy validation, an appropriate standard operating procedure or a detailed validation plan should be written. This plan can be a stand-alone document or can be contained in a laboratory notebook or some comparable format. The documentation should clearly state the intended use of the method and a summary of the performance parameters to be validated. The plan should include a summary of the proposed experiments and the target acceptance criteria for each performance parameter evaluated. 

The laboratory notebook is a record of your job as an analytical chemist. It documents everything you do. It is the source for reports, publications, and regulatory submissions The success or failure of a company s product or service may depend oh how well you do that documentation. The notebook, becomes a legal document for patent issues, government regulation issues (validation, inspections, legal actions), and the like. Remember, if it isn t written down, it wasn t done. The notebook is where you record your orig- inal ideas thatmay form the basis of a patent arid so it is important to record what went into those ideas and when. 

The excipient manufacturer should establish and maintain procedures to control and verify the design of the excipient to ensure that the specified requirements are met All information concerning the design process should be documented as part of a product design report or to be easily cross-referenced (e.g., computer records, laboratory notebooks, etc.). 

It is preferable that records of work documents such as laboratory notebooks and recordings, required by the regulations, be stored in the laboratory itself. 

Documents and other records, including original data such as laboratory notebooks should be retained for at least one year after expiry date of the batch. Documents should be easily retrievable. 

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