Annexure I

1. Brief Description:

Annexure I provides a detailed flow-chart-based approach for evaluating changes that may affect cleaning validation. It covers the introduction of a new product, assessment of product hazards, toxicological data and PDE, selection of worst-case products, calculation of MACO limits, and evaluation of analytical method capability including LOD and LOQ. The annexure also considers product solubility, cleanability and therapeutic dose to determine the overall risk and cleaning validation requirement. It provides guidance for evaluating new equipment, including design, capacity, product-contact surface area and difficult-to-clean locations. Additionally, it addresses shifting products to other equipment or manufacturing areas and assesses the effect on existing MACO limits. Changes in batch size are also evaluated for their impact on previous cleaning validation status. Overall, Annexure I ensures that changes are scientifically assessed, documented and, where necessary, supported by cleaning validation, revalidation, SOP revision and personnel training.