1. Introduction and scope 116
2. Glossary 116
3. Chromatographic systems 118
4. Qualification, validation, maintenance and calibration 119
5. Access and privileges 119
6. Audit trail 120
7. Date and time functions 120
8. Electronic systems 121
9. Solvents, buffer solutions and mobile phases 121
10. Column management 122
11. Sample management and sample set 122
12. Chromatographic methods (acquisition and processing) 124
13. Peak integration 125
14. Data management 126
References 126
Further reading 127
1.1 The use of chromatography methods such as high-performance liquid chromatography, also referred to as high-pressure liquid chromatography (HPLC), and gas chromatography (GC) in quality control laboratory analysis has increased significantly in recent years. Observations during inspections have shown that there was a need for a specific good practices (GXP) document.
1.2 HPLC and GC methods are used in, for example, the identification of materials and products, for determination of assay and related substances in materials and products, as well as in validation such as process validation and cleaning validation. Note: Although thin-layer chromatography methods are also used, this approach is not specifically addressed in detail in this document.
1.3 Owing to the criticality of the results obtained through chromatography, it must be ensured that the data acquired meet ALCOA+ principles (i.e. attributable, legible, contemporaneous, original and accurate, with additional emphases [see Glossary]).
1.5 This document provides information on GXP to be considered in the analysis of samples when chromatographic methods and systems are used. The principles should be applied in the analysis of, for example, raw materials, starting materials, intermediates, in-process materials and finished products.
1.6 The principles contained in this guideline are applicable to general chromatographic analysis used in, for example, assay determination, testing for related substances and impurities, process validation, cleaning validation, cleaning verification and stability testing.
2. Glossary
The definitions given below apply to the terms used in this guideline that are not defined in existing WHO terms and definitions databases. They may have different meanings in other contexts. Note: For general definitions relating to chromatography, see the relevant pharmacopoeia recognized by the national medicines regulatory authority.
ALCOA. A commonly used acronym for “attributable, legible, contemporaneous, original and accurate”.
ALCOA+. A commonly used acronym for “attributable, legible, contemporaneous, original and accurate” that puts additional emphasis on the attributes of being complete, consistent, enduring and available – implicit basic ALCOA principles.
audit trail. A form of metadata that contains information associated with actions that relate to the creation, modification or deletion of GXP records. An audit trail provides for secure recording of life-cycle details such as creation, additions, deletions or alterations of information in a record, either paper or electronic, without obscuring or overwriting the original record. An audit trail facilitates reconstruction of the history of such events relating to the record, regardless of its medium, including the “who, what, when and why” of the action.
back-up. A copy of one or more electronic files created as an alternative in case the original data or system are lost or become unusable (for example, in the event of a system crash or corruption of a disk). It is important to note that back-up differs from archival, in that back-up copies of electronic records are typically only temporarily stored for the purposes of disaster recovery and may be periodically overwritten. Such temporary back-up copies should not be relied upon as an archival mechanism.
calibration. The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard.
Limits for acceptance of the results of measuring should be established.
data. All original records and true copies of original records, including source data and metadata and all subsequent transformations and reports of these data, that are generated or recorded at the time of the good manufacturing practices (GMP) activity and allow full and complete reconstruction and evaluation of the GMP activity. Data should be accurately recorded by permanent means at the time of the activity. Data may be contained in paper records (such as worksheets and logbooks), electronic records and audit trails, photographs, microfilm or microfiche, audio- or video-files, or any other media whereby information related to GMP activities is recorded.
data integrity. The degree to which data are complete, consistent, accurate, trustworthy and reliable and to which these characteristics of the data are maintained throughout the data life-cycle. The data should be collected and maintained in a secure manner, such that they are attributable, legible, contemporaneously recorded, original or a true copy and accurate. Assuring data WHO Expert Committee on Specifications for Pharmaceutical Preparations Fifty-fourth report integrity requires appropriate quality and risk management systems, including adherence to sound scientific principles and good documentation practices.
metadata. Data about data that provide the contextual information required to understand those data. Metadata necessary to evaluate the meaning of data should be securely linked to the data and subject to adequate review.
Examples of metadata include the time/date stamp of an activity, the operator identification (ID) of the person who performed an activity, the instrument ID used, processing parameters, sequence files, audit trails and other data required to understand data and reconstruct activities. qualification. Documented evidence that premises, systems or equipment are able to achieve the predetermined specifications, are properly installed, and/or work correctly, and lead to the expected results.
sample set. The combination of samples, standards and blanks prepared for analysis, which includes the specified sequence to be injected or analysed.
source data. Original data obtained as the first-capture of information, whether recorded on paper or electronically.
validation. The action of proving and documenting that any process, procedure or method actually and consistently leads to the expected results.
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