It is a practical fact that a drug product is not produced by itself at the point of use. Instead, the pharmaceutical product is manufactured with a system designed and built for this purpose. Although the manufacturing process varies slightly between drug product and drug product vendors, the process usually consists of steps that perform the following functions:
During the manufacturing process, the lead solution for the drug product (called process flow) comes into contact with the materials and components that make up the production equipment. Since these components (filters, filter housings, tubing, disposable bioreactors, storage bags, mixing systems, disposable lyophilization trays, impellers, connectors, chromatographic columns and column housings, etc.) are not chemically inert, the process flow will interact with the components.
As with packaging, this interaction can cause substances to flow out of the components. If these substances persist throughout the manufacturing process, they will become foreign impurities in the packaged drug product, where they can have the same potential adverse effects on the drug product's suitability for use as packaging-associated leaks. Foreign impurities from manufacturing are called leaks (PerL) associated with process equipment to distinguish them from leaks from packaging.
While the inactivation of manufacturing systems is a global regulatory requirement (for example, in 21 CFR section 211.65 “Equipment should be constructed in such a way that surfaces in contact with components, in-process materials, or drug product be constructed in a reactive, non-additive manner) or the safety, identity of the drug product. can be absorbent, changing its strength, quality or purity beyond formal or other specified requirements… ”) It is well known that absolute inertia cannot be achieved. Therefore, the relative inertia should be demonstrated by determining that the magnitude of the interaction between a manufacturing system and the process flow will not adversely affect the PerLs contained in manufactured drug products, the suitability of the product for its intended use.
While not a regulatory requirement, relative inertia should also be demonstrated by ensuring that the efficiency of the production process is not reduced by substances that leak into the process stream.
While regulations establish the requirement for chemical assessment of production equipment, they do not specify the tools required to perform such an assessment. To bridge this gap, various industry groups [e.g. component suppliers (BioProcess Systems Alliance, BPSA) and component users (BioPhorum Operations Group, BPOG)] have published good practice recommendations and the USP provides information on the selection and qualities of materials and components both applicable and used in manufacturing. published monographs. (<665> and <1665> respectively).
While these efforts are to design, implement, report and interpret the correct chemical assessment for a manufacturing component, it is not an intuitive or trivial matter. Although chemical assessment may involve extractable and leaky tests, proper assessment requires effective risk analysis, prudent and justified testing, and well thought out data interpretation.
The practical consequences of a poor chemical assessment are significant, measured in lost time, excessive costs and delays in obtaining regulatory approvals. EUROLABWith extensive and successful experience in developing, performing, interpreting and reporting chemical assessments, including extractables and leachable studies, , can design, conduct and report an expertly tailored customized approach to suitability for specific use issues.
EUROLAB, with its highly expert team and internationally accredited laboratories, Production Systems Tests It performs all test, analysis, measurement, evaluation and report generation services completely and reliably.
To get an appointment, to get more detailed information or to request an evaluation, you can ask us to fill in our form and reach you.
