GMP for Quality Control
A large number of GMP regulations must be complied with in pharmaceutical quality control, and it is foreseeable that these requirements will continue to increase in the coming years. For the years 2023/2024 alone, two new or revised guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) with aspects on quality control have been announced. For example, the new ICH Q14 specifies requirements for method development, while the revised ICH Q2(R2) provides more detailed requirements for the scope of method validation.
Interdisciplinary Valicare teams of experienced and highly qualified biologists, chemists, engineers and pharmacists have successfully completed a large number of customer projects in the field of quality control in recent years. Our experts provide cross-thematic advice and support in all aspects of quality control. This includes the actual set-up and establishment/development of a quality control system, risk management, qualification of equipment and rooms as well as the definition of specifications and the validation of processes and methods up to the correct documentation and testing during implementation.
For the years 2023/2024 alone, two new or revised guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) with aspects on quality control have been announced
In quality control, as in other regulated areas, risk analyses must be performed on a wide range of issues. The qualification of analytical equipment, the development and validation of analytical methods, the preparation of instructions and protocols and last but not least the definition of in-process controls and specifications are based on risk analyses. For more information regarding our risk-based approach services, please click here.
Valicare advises you on the development or adaptation of control strategies for your active ingredient or finished drug product based on the identification of Critical Process Parameters (CPP) and Critical Quality Attributes (CQA). As an independent consulting service provider, we use an objective perspective and develop the necessary recommendations for action.
Based on the process and issues, we already advise and support you during the development phase in your laboratories. Based on our many years of experience, we can recommend the laboratory equipment suitable for the methods. If you would like to outsource quality control or require very specialized analytical methods, we will suggest suitable certified service providers.
The control strategy must combine the findings from the impurity profile, the intended use, the risks for the presence of carcinogenic and mutagenic impurities, and other regulatory requirements.
For the control strategy, standardized procedures can be used for many parameters, such as heavy metal contamination or microbial contamination. Unfortunately, more complex considerations are necessary for the development of the control strategy of the impurity profile with regard to structurally related substances, as well as for possible carcinogenic or mutagenic low-molecular compounds, as they can also occur in biologicals and ATMPs due to the process. The first step is to identify potential impurities. Based on theoretical considerations, it is possible to predict which impurities can be expected, but experimental verification is absolutely necessary.
The working techniques for further clarification differ depending on the type of impurity and the type of active ingredient. For small molecule drugs and small molecule impurities, different working techniques are necessary than for biologicals and ATMPs.
When developing a control strategy with regard to low-molecular impurities, different orthogonal separation techniques must first be selected, which are combined with suitable detectors - for the expected and still unknown impurities. In the case of process-related expected carcinogenic or mutagenic impurities, these need to be procured as standard substances, if available, in order to keep them as reference substances. For detection, UV adsorption can be used in the simplest case, but this requires a suitable chromophore in all potential analytes. In addition, it is often necessary to select other detection principles, each of which has advantages and disadvantages. Detection by means of an evaporative light scattering detector (ELSD) or mass spectrometry (MS) may be necessary in special cases, whereby a variety of methods are summarized under this umbrella term.
Appropriate risk minimization measures must always be considered in the control strategy. Further aspects on this topic can be found here.
In the case of biologicals and ATMPs, in addition to the consideration of possible low-molecular impurities, further techniques for related substances must be applied in some cases. The analytical techniques with regard to related substances for biologicals and ATMPs are very broad due to their complexity. This is especially the case for ATMPs involving cells and/or cellular components. The necessary techniques/methods range from chromatographic methods, such as High Performance Liquid Chromatography (HPLC) and Capillary Electrophoresis (CE), which can be used, for example, for the determination and analysis of proteins, antibodies, gene therapeutics, to Polymerase Chain Reaction (PCR) analyses and flow cytometric analyses, which are for example necessary for cell therapeutics. A special role has the characterization of different cells/cell types based on the basis of specific surface proteins, which can be detected and quantified with fluorescence-coupled antibodies. Fluorescence-Activated Cell Sorting (FACS) allows to select and separate specific cells from a heterogeneous cell population based on specific surface properties. Further examples here include analytics with respect to Host Cell Proteins (HCP) by HPLC/CE-MS, detection of incorrect sequences in a mRNA therapeutic, or functional assays to screen for specific properties or interactions of cells or cell components, such as immunosuppression.
Control strategies for ATMPs or their intermediates need to be implemented especially when release testing cannot be performed on the active substance/finished product for technical reasons or when it is not available in sufficient quantities.
Appropriate risk minimization measures must always be considered in the control strategy. You can view further aspects on this topic here.
Valicare offers qualifications not only for equipment, facilities and clean rooms in pharmaceutical production, but also in the field of quality control. In cooperation with the customer and on a risk-based approach, we determine the qualification scope. On demand we can draw on documents created by our self, regardless of the manufacturer, or use customer-specific documents. Based on your requirements and questions, we offer services ranging from consulting to the execution of individual subtasks to complete qualification campaigns. Benefit from our experience won through a large number of successfully implemented qualification projects. As part of the qualification project we can also perform computer system validation.
For more information about risk-based qualification, click here.
Valicare has been offering a wide range of services in the field of analytical method validation for several years now. Starting with training courses, consulting and the preparation of specification documents, we also offer support in the planning, documentation, evaluation and interpretation of validation results. For more information on our scope of services in the field of analytical method validation, please click here.