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What is the purpose of written procedures?

Procedures provide instruction to the user and are reviewed and approved by management and quality assurance
A periodic schedule of review and revision is established for all procedures
Furthermore, written procedures facilitate a quality audit that takes place after the study is complete


What are SOPs?

A testing facility shall have standard operating procedures in writing setting forth nonclinical laboratory study methods that management is satisfied are adequate to ensure the quality and integrity of the data generated in the course of a study


Key SOPs include:

Document control, training and qualification of analysts, procedures for recording raw data, corrective and preventive actions, change control, and quality assurance monitoring of GLP studies
Purpose of SOPs: describe how to perform tests or activities not normally specified in detail in study plans or test guidelines


Categories of activities SOPs are available:

Test and reference items, apparatus, materials and reagents, record keeping, reporting, storage, retrieval, test system and quality assurance procedures


Essential elements of SOP:

Purpose, responsibility of personnel, reference to other related documents, materials, equipment, procedure (step by step), approval


What is a written protocol?

Each study shall have an approved written protocol that clearly indicates the objectives and all methods for the conduct of the study
The protocol is finalized and approved before the start of the study
Study specific material that is generally not included in the SOPs is included in this document, such as details of the experimental design


What are analytical test methods?

Highly specific lab instructions are written into analytical test methods
Each lab shall have immediately available lab manuals and SOPs relative to the lab procedures being performed, published literature may be used as a supplement to SOPs
Changes are annotated on the change control page of the method along with the justification for each change


What does the study final report include?

A statement of the objectives of the study
A description of all methods employed
All of the experimental data and results generated in the conduct of the study
Descriptions of all calculations
All conclusions drawn
Compliance statement attached


What is raw data?

Raw data is any lab worksheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities of a non-clinical lab study and are necessary for the reconstruction and evaluation of the report of that study
All raw data must be defined, recorded and retained as part of the study


What is the difference between raw data and the media used to record it?

The raw data is the same (recorded weight)
The media used to record it are different (LED display and printer)


Using media to record

If the LED display is defined as the raw data, then the measurements must be directly recorded into workbooks or notebooks
However, if the lab defines the ink on paper printout to be the raw data from the balance, the analyst should immediately paste it into his or her workbook


How to record raw data in a workbook

It is typical to write the date and the name or initials of the analyst across the seam of the print out and the page, thereby further integrating the printout and workbook or notebook
The analyst will write on the printout sample identification information


Entering in the unaltered raw form

Data must be entered in the unaltered raw form. It is expected that both the raw data, which is the weight of the standard and the volume of solution or solvent, and the calculated value both be recorded and that an example of the calculation (including appropriate units and considering the significant figures convention) be shown in the workbook or notebook


Data storage

If the analytical balance is not capable of electronically storing the result, then the procedure to verify that the balance printout and the LED display are the same is easy to perform and document
If, instead, the balance is capable of retaining in electronic memory (for printing at a later date) the old weight while generating a new weight, then the question arises:
What protects against confusing old with new data, altering or deleting data, or losing data when power to the balance fails?


Data retrieval

Require disaster recovery to protect against the power failure or to mitigate its impact on studies e.g. cell culture multiple vials, store in more than one freezer, hard drive for images/ documents storage
Require log on with password control


GLP data storage and retrieval

The same principles of data storage and retrieval under GLP apply, whether the media used for storage is ink on paper or not
Systems that store data in electronic form, e.g. computer systems and lab information management systems must meet the same requirements as ink on paper systems


Demonstrating trustworthy and reliable records

To demonstrate to the FDA that the electronic record is trustworthy, reliable and generally equivalent to paper records, the lab must comply with the regulations set forth in Title 21, Code of Federal Regulations, Part 11, which among other things dictate the level of control that the lab must have over the electronic record and the extent that the computer system generating this record must be validated


Reconstructing the study

In addition to results, form the measurements it will typically be required to reconstruct the study
Examples include instrument condition and parameters, records of instrument performance issues and investigations into suspect data


Good documentation practices

Importance placed on documenting a study
In 1990, 2 to 15 volumes of summary material generated during the safety and efficacy investigations and manufacturing and analytical testing would have 10 to 100 volumes of raw data to support the summary
This magnitude should serve as a benchmark, all fo this information must be properly documented for a drug to be approved by the FDA


Attributable raw data

It is expected that raw data be attributable, legible, contemporaneous, original and accurate
By attributable, it means that the data are linked to their source, including the person making the observation and the record and the study, test article, instrument and analytical run


Tracing the person making the data entry

It is a GLP requirement that the person making the data entry shall sign or initial the entry on the date it was recorded
Similarly, in automated data collection systems, the person responsible for direct data input shall be identified at the time of data input


Contemporaneous and original data

Contemporaneous data- data are recorded at the time the observation is made
Original- the first recording of the data, which is assumed to be the most accurate and reliable recording of the data; following good documentation practices helps to instil these quality attributes


Changes to data entries

Changes can be made to data entries but they must not obscure the original entry and they must, at the time the change is made, be signed or initialled and dated by the person making the change, who must also record the reason for the change


Error codes

To facilitate changes to data entries, many labs create error codes that are defined in a SOP, and simply write the error code alongside the change rather than use a full sentence
E.g. MD might be used for misdated


Examples of good documentation practices

Record all data and observations legibly in indelible ink (except those generated by automatic data collection systems)
Enter all data directly into lab workbooks at the time of observation, do not record any data on scraps of paper that can be lost
Date and sign or initial all entries in workbooks, logbooks or notebooks


Exact copies

Exact copies of original can be included and should be marked as such and signed and dated
Exact copy printouts from automatic data collection systems must contain all the information that is in the electronic record such that the experiment can be reconstructed



To facilitate the orderly recording of raw data, most labs use a workbook or notebook
The notebook is a research notebook, issued to the research analyst and tracked by a notebook number assigned by the document control unit
The notebook consists of many bound, prenumbered blank pages and a space for the analyst and witness to sign and date each page
The notebook is usually not specific to the analysis or the study and the analyst is expected to keep it until it is filled



The workbook is also pre-printed with a document control number that is issued and controlled by the document control unit
The workbook template is created by the lab with a specific analysis in mind
Revision to the workbook template goes through a change control programme that tracks all changes to lab operating procedures; therefore workbook template revisions must be justified from both a scientific and a compliance viewpoint


Examples of information required in workbooks and notebooks to document the study and analysis

Analyst name, date, document control number, method or protocol number, study number, test specification or ranges, objective or purpose, sample information, reference standard information, reagents list, instrument list, preparation of diluent and mobile phases, reporting results, instrument setup and parameters, preparation of stock and working standards, preparation of samples, calculations



Contain information supporting multiple GLP studies, making the ability to easily associate certain data or information with a certain study important in reconstructing study construct
Written records shall be maintained of all inspection, maintenance, testing, calibrating and/or standardization operations performed on equipment and instrumentation used in the generation, measurement or assessment of data and equipment used for facility environmental control


Examples of information included in instrument logbooks

Instrument identification number
Date of installation qualification
Details of the performance qualification
Instrument type or description
Qualification status
Identification of the SOP
Date of the last calibration


The archives

It is a regulatory requirement that all study materials required for the reconstruction of the study be archived
In deciding what to archive, one must consider the obvious e.g. all the study raw data, study protocol and report, and those things required to prove that the study was conducted in compliance with GLP
Study materials are typically archived for 10 years