Quality control (QC) is a central aspect in the manufacture of active ingredients and medicinal products and is essential to ensure and demonstrate product quality
Valicare offers extensive services for GMP-compliant quality control.
In pharmaceutical quality control, a large number of GMP regulations must be complied with and it is foreseeable that these requirements will increase continuously in the coming years. For 2021 and 2022, four new or revised International Council of Harmonisation (ICH) guidelines with aspects of quality control have already been announced. For example, the new ICH Q14 will stipulate a guidance for method development, while the revised ICH Q2(R2) will provide more detailed requirements on the scope of method validation.
Valicare with its interdisciplinary teams of experienced and highly qualified biologists, chemists, engineers, and pharmacists has successfully completed a large number of quality control projects for numerous clients.
Our experts advise and support you in all aspects of quality control manufacturer-independent. They assist with proper set-up, establishment/development of a quality control system, risk management, qualification of equipment and premises, definition of specifications, validation of analytical methods and processes, as well as correct documentation and testing prior to implementation.
Due to the broadly based focus of our experts, we offer our services in the field of small molecules as well as for Advanced Therapy Medicinal Products (ATMPs) specifically. We accompany projects in all development phases, starting with new active ingredients (New Chemical Entity, NCE; Novel Biological Entity, NBE; Investigational New Drug, IND) through clinical studies and approval to questions regarding market supply.
Risk Management in QK
In quality control as well as in other regulated areas, risk analyses must be performed on a wide range of issues. Qualification of analytical equipment, development and validation of analytical methods, preparation of instructions and protocols, and definition of in-process controls and specifications are based on risk analyses. Further information regarding our services for risk-based approaches can be found here.
Developing/Adapting a Control Strategy in QC
Valicare advises you on the development or adaptation of control strategies for your active ingredient or finished drug based on the identification of critical process parameters (CPP) and quality attributes (CQA). As an independent consultancy service supplier, we objectively support our customer right from the beginning.
Depending on the processes and issues, we advise and support you during the development phase in your laboratories and recommend suitable laboratory equipment needed based on our long-term experience. If you intend outsourcing of QC or require special analytical methods, certified service providers (outsourced activities) can be recommended and qualified by Valicare.
The control strategy must combine findings from the impurity profile, intended use, 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 contamination with heavy metals 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. In the first instance, possible impurities are identified. Based on theoretical considerations, it is possible to predict which impurities can be expected, but an experimental verification is still necessary.
The working techniques for further clarification differ depending on the type of impurity and the type of active substance. For small molecule active ingredients and small molecule impurities, different working techniques are necessary than for biologicals and ATMPs.
Special Aspects of the Control Strategy for Low-Molecular-Weight Impurities
The development of a control strategy with respect to low molecular weight impurities first requires the selection of different orthogonal separation techniques, which are combined with suitable detectors – for the expected and possible unknown impurities. In the case of process-related possibly expected carcinogenic or mutagenic contamination, these are to be procured as standard substances, if possible, in order to keep them as reference substances. In the simplest case, UV adsorption can be used for detection, but this requires a suitable chromophore in all potential analytes. In addition, it is often necessary to select other detection principles taking into account their advantages and disadvantages. For example, based on the research question, detection by Evaporative Light Scattering Detector (ELSD) or mass spectrometry may be required, whereas a variety of methods are summarized under this umbrella term.
Appropriate risk minimization measures must always be included in the control strategy. Further aspects on this topic can be found here.
Special Aspects of the Control Strategy for Biologicals and ATMPs
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 chronographic methods such as high performance liquid chromatography (HPLC) and capillary electrophoresis (CE), which can be used for the determination and analysis of proteins, antibodies and gene therapeutics, to polymerase chain reaction (PCR) analyses and flow cytometric analyses, which are necessary for cell therapeutics, for example. A special role has the characterization of different cells/cell types based on specific surface proteins, which can be detected and quantified with fluorescence-coupled antibodies. Using fluorescence-activated cell sorting (FACS), which is an application of this principle, it is possible to select and separate certain cells from a heterogeneous cell population on the basis of specific surface properties. Further examples are the analysis of host cell proteins (HCP) by HPLC/CE-MS (mass spectrometry), the detection of incorrect sequences in a mRNA therapeutic or functional assays to test certain 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. Further aspects on this topic can be found here.
Qualification and Validation in QC
Valicare offers qualifications not only for equipment, plants/lines and premises in pharmaceutical production, but also for about ten years in the field of quality control. Based on risks, we determine the necessary scope of the qualifications together with customers. Here, we can access our own documents from a large number of successfully completed qualification projects. Based on your requirements and questions, we offer services ranging from consulting to the execution of individual subtasks to complete whole qualification campaigns. In addition, as usual for quality control, we can also carry out computer system validations during qualification process.
Further information on risk-based qualification can be found here.
Method Validation in QC
Valicare has been offering a wide range of services in the field of analytical method validation for several years. Starting with training courses, consulting and preparation of specification documents, we also offer support in the planning, documentation, evaluation, and interpretation of validations. Further information on our service range in the field of analytical method validation can be found here.