Manufacturing process changes

Manufacturing process changes to simplify production technologies, reduce water and energy use, or introduce closed-loop recycling and... 

Manufacturing process changes involving synthetic steps through the final intermediates... 

Manufacturing process changes are those that encompass a wide range of process-related changes, from the use of different equipment to changes in synthetic components and procedures. Such changes are considered to be CBE-type changes. 

Manufacturing process change New validation protocol Stability protocol revisions for expanded accelerated and long-term stability Update methods validation Master and batch record revisions Methods and specifications revisions... 

Verification of approved manufacturing process changes to marketing authorizations/approved applications [24]... 

X-ray diffraction is used to quantify the crystalline species such as zeolite, alumina, and kaolin in raw materials and finished products. Such information is used not only by research scientists, but also by quality assurance personnel during the manufacturing process. Changes in any of these materials can affect the catalysts performance and cost, therefore they must be precisely controlled. 

In general, a simple formulation is used to deliver the test substance to the experimental animals. This formulation is usually not the same as the final market formulation and any manufacturing process changes made during the course of the different development phases of the product should always be evaluated with respect to earlier data obtained. Product comparability will need to be established. Previous data may no longer be (fully) representative and sometimes parts of the preclinical (or even early clinical) studies have to be repeated, replaced or annexed by additional studies. Obviously, in view of time and costs involved, one would like to avoid this kind of situation as much as readily possible. 

Small-molecule manufacturing is also a system of checks and balances in which any small increase or decrease in reaction step performance can have consequences downstream. As always, patient safety is of utmost concern. Any manufacturing process changes that alter an impurity level or introduce a new impurity, even as low as 0.1%, may necessitate additional toxicity studies and documentation for review and registration. In addition, an improvement in reaction efficiency may alter bulk product crystallinity or polymorph composition that can affect formulation and human pharmacokinetics. Once process parameters are finalized, the ultimate manufacturing step involves selection of a manufacturing site, transfer of the process, and preparation of a demonstration batch followed by a minimum of three consecutive validation batches of API to demonstrate that the synthesis of material can be controlled within analytical specifications and reproducibility. 

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