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    Home > Medical News > Latest Medical News > The quality of the analytical methods in the analysis method development guide series is derived from the design

    The quality of the analytical methods in the analysis method development guide series is derived from the design

    • Last Update: 2020-12-24
    • Source: Internet
    • Author: User
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    To ensure the safety, effective and quality control of drugs is the basic principle to be followed in drug research and development and evaluation, among which, quality control of drugs is the basis and prerequisite to ensure the safety and effectiveity of drugs.
    in order to achieve the goal of quality control, it is necessary to control drug quality from many angles and levels, that is to say, to carry out multiple project tests on drugs to comprehensively examine drug quality.
    , when establishing quality standards, analytical methods need to be developed if there are no statutory standards to refer to.
    in the pharmaceutical production process changes, preparation parts changes, quality standard analysis methods need to be based on the extent of change risk assessment, if necessary, start the re-development of analytical methods.
    In order for the test results to be accurate and reliable, the risks of the scientificity, accuracy and feasibility of the analytical methods developed must be assessed during method development to fully demonstrate that the analytical methods meet the objectives and requirements of the test project.
    method development is to establish a scientific and reasonable analysis method to effectively control the intrinsic quality of drugs.
    In essence, method development is based on the requirements of the testing project, combined with the nature of the material itself, relevant research data, corresponding guidelines and basic theories, the parameters of the method for scientific and reasonable design, and with appropriate tests to confirm whether the design is true, through the iterative design and confirmation process to determine the parameters of the method, in accordance with the principles of risk management to carry out systematic research and evaluation of the parameters of the method, through the design of reasonable tests to confirm whether the analytical methods used can meet the requirements of the test project, and formulate reasonable acceptable standards.
    To make the output of a research activity, the analytical method needs to evaluate the quality of the analytical method from multiple dimensions, including but not limited to the following aspects: 1, whether the technology is scientific, reasonable and feasible;
    quality of the analysis method comes from the process of design (QbD) analysis method development is not a trial-and-error process, but a systematic and structured design process, an iterative process of design and confirmation with risk management as its core.
    the quality of analytical methods should be scientifically and rationally designed based on the concept of "quality derives from design (QbD)" and the risks in the entire life cycle of the analytical methods should be fully evaluated.
    analysis method as an output of method development, as other products, the application of quality comes from the design of related concepts, such as life cycle, risk management, design space and so on.
    as an output in drug research and development, the analysis method should adopt the appropriate management strategy at different stages of life.
    of life cycle management of analytical methods provides a new way of thinking for traditional analytical validation, validation, and transfer, treating these activities as continuous, closely related rather than discrete.
    The development of analytical methods needs to pay attention to the risk management of the whole life cycle of the analytical methods, identify the relevant risks from technology, communication, stakeholder needs and other aspects, and make reasonable and necessary responses, check the secondary and residual risks after the response, and assess the effectiveness and rationality of risk management.
    should evaluate the tolerance of analytical methods to risks throughout the life cycle as part of the quality evaluation of analytical methods.
    In order to ensure that the analytical method has the appropriate tolerance to the risk, the analysis method should allow the detection conditions to change within a certain range, the resulting test results are still stable, that is, the common variable conditions should allow fluctuations within a reasonable range, such as ambient temperature, humidity, equipment model, sample properties, instrument parameters, operating level, etc.
    the development of analytical methods, it is necessary to design the space in which the analytical method conditions allow for change, and it is generally not appropriate to prescribe too strict experimental conditions.
    , structured design and analysis method development mainly includes material handling, experimental parameters, system applicability test, calculation method, acceptable standards and other five aspects of the selection process.
    1. Material handling Material handling refers to the study of the treatment methods of materials involved in the testing process, such as test products, control products, etc., including the selection of parameters such as thinner, material dosage, test concentration, control concentration, operation method, etc.
    method development process, the material handling method should be systematically studied and evaluated, and the parameters of material handling should be made scientifically and rationally.
    diluent analysis method refers to when it is mixed with the material, it can change the material shape to meet the relevant testing requirements.
    can be solvents, solutions, solid powders, etc.
    Diluents should be able to mix well with relevant materials, such as liquid thinners and materials to form a solution, should have a certain solubility, diluents should be inert in the analysis method, or the impact on the results of the analysis is small, can be eliminated with blank tests, materials in the thinner should be stable for a reasonable period of time.
    general, thinners should choose safe reagents, preparation methods are simple and have good stability.
    Material Dosing Drug testing evaluates specific attributes of the population based on the test results of the sample, and the risk of whether the sample taken represents the population needs to be evaluated, so the sampling method and dosing of the material should be studied to indicate or prove that the sample taken under a particular test can represent the population.
    test, control product concentration test results need to have a more obvious response enough for analysts to make a judgment, so the test, control should be by the appropriate concentration, in the test process to produce an appropriate response.
    in the formulation of test products, control concentration should be based on acceptable standards, equipment, system applicability tests, calculation methods and other relevant content of the constraints of comprehensive consideration.
    For example, in the course of the study of the test-supply concentration of the substance concerned, in addition to making the sensitivity of the method and the separation of the various parts meet the requirements, it is necessary to meet the requirements of the calculation method, such as the area normalization method needs to prove that the responder of the test-making concentration is within the linear range.
    For the operation method of material handling, you need to evaluate the risk to the detection results.
    such as the effect of the ionity of dissolved operation solution on the test results, the effect of layered extraction on accuracy, etc.
    2, experimental parameters The selection of experimental parameters should be carried out the necessary research, scientific and reasonable explanation of the selection process.
    can use risk management to conduct corresponding research, study high-risk parameters in detail, and formulate appropriate coping strategies.
    Taking liquid chromatography as an example, the selection of parameters such as flow phase, chromatography column, sample volume, flow rate, escape procedure, column temperature, wavelength and so on should be assessed and responded to according to theory, experience, etc., and the rationality of the coping strategy should be proved by experimental data if necessary.
    such as the wavelength of the detection results of the risk is very high, reasonable wavelength selection can reduce the risk, wavelength selection of the risk is acceptable, can be linear, repeatability and other research data to confirm.
    3, the system applicability test analysis method of the entire system contains samples, equipment and other content may be different from the method development and verification period, and this difference during the system applicability study recognized as a high-risk factor, may cause serious deviation from the test results, the corresponding test should be developed to distinguish the difference.
    4, calculation method The calculation method in the analysis method needs to be suitable for material processing, experimental parameters and other content, if necessary, the experimental data to confirm whether the proposed calculation method is applicable.
    e.g. the peak area normalization method to calculate the results of the substances concerned, the response value of the test concentration should be within a linear range, if it is proposed to use the self-control method of the correction factor to calculate the results of the substances concerned, it is possible to prove that the correction factors of each known impurity are within the appropriate range.
    5, acceptable standards for drug-related testing projects are mainly considered from the perspective of safety and quality control.
    acceptable standards for safety-related testing projects, such as substances, residual solvents, elemental impurities, genotoxic impurities, microbial limits, etc., shall be established in accordance with the relevant guidelines.
    If general impurities exceed the defined limits set out in the Guidelines, the new drug shall explain the reasonableness of the limits from the relevant safety data for animal trials and clinical trials or reference to the relevant guidelines;
    acceptable standards for other testing items, such as moisture, melting point, cyclone, content determination, etc., if there is no impact on safety effectiveness, reasonable limits shall be established according to the actual quality level that may be achieved.
    , systematic design needs and can be clear that the analysis method of any one parameter selection is not isolated.
    the design of method parameters, we should consider the impact of this parameter on all aspects, including technical aspects, stakeholders, laboratory management, etc.
    such as limits will affect the selection of sample processing, calculation methods, test parameters, system applicability tests and other parameters.
    To develop NDMA testing methods in a drug, for example, its PDE is 96 ng/D, which requires very sensitive detectors such as mass spectrometry, very high concentrations of test solution, which also means that the solubility of thinners is very high. It is required that the calculation method generally does not apply the peak area normalization method, and if the content determination method of a drug is developed with a limit of 98.0% to 102.0, the selection of other parameters may be completely different from the NDMA detection method.
    method parameter design is also the need to consider the potential impact of stakeholder needs and behavior, assess the possible risks of each parameter in the life cycle of the analysis method, and confirm that the analysis method has sufficient risk tolerance.
    related content can be found in the stakeholder management and risk management section of the analysis method.
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