Quality control (QC) ensures product quality

Valicare advises you on the development or adaptation of control strategies for your active ingredients or finished drug products 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 your process and issues, we already start advising and supporting you during the development phase in your laboratories. We have the experience to recommend the right laboratory equipment. In case you want to outsource quality control or require very specialized analytical methods, we will suggest suitable certified service providers.

Develop suitable control strategies for impurities

A good 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.

Standardized procedures can be used for many parameters, such as heavy metal contamination or microbial contamination. Unfortunately, more complex considerations are required to develop a 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. The first step is to identify potential impurities. Although theoretical considerations make it possible to predict certain impurities, experimental verification is still necessary.

The working techniques for further clarification differ depending on the type of impurity and the type of active ingredient. Small molecule drugs and small molecule impurities require different working techniques than biologicals and ATMPs.

A control strategy regarding low-molecular impurities requires the selection of different orthogonal separation techniques, which are combined with suitable detectors for the expected and still unknown impurities. Process-related expected carcinogenic or mutagenic impurities, need to be procured as standard substances, if available, in order to keep them as reference substances. UV adsorption can be used for detection in the simplest case, but 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 case of biologicals and ATMPs, further techniques for related substances must be applied in some cases in addition to the consideration of possible low-molecular impurities. The analytical techniques regarding 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 techniques/methods range from chromatographic methods, such as High Performance Liquid Chromatography (HPLC) and Capillary Electrophoresis (CE), which can be used to determine and analyze proteins, antibodies, and gene therapeutics, to Polymerase Chain Reaction (PCR) analyses and flow cytometric analyses, which are for example required for cell therapeutics. The characterization of different cells/cell types based on specific surface proteins, which can be detected and quantified with fluorescence-coupled antibodies, plays a special role. Fluorescence-Activated Cell Sorting (FACS) allows to select and separate specific cells from a heterogeneous cell population based on specific surface properties. Further examples 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 cleanrooms in pharmaceutical production, but also in the field of quality control. Together with our customers, we determine the qualification scope on a risk-based approach. We can draw on our own documents or on user-specific ones. Our services range from consulting to the execution of individual subtasks to complete qualification campaigns. We can also perform computer system validation as part of the project. Benefit from our experience gained in successfully implemented qualification projects.

For more information about risk-based qualification, click here.

Method validation in quality control

Valicare has been offering a wide range of services in the field of analytical method validation for several years. Apart from training courses, consulting, and the preparation of specification documents, we also offer support in 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.