Abstract
Manufacturing process validation of products used in clinical investigation is the regulatory requirement. Production must be prospectively validated to confirm the suitability of the product intended use. The validated process and data are crucial for the Chemistry, Manufacturing and Control (CMC) section of the Investigation of New Drug submission. Effective validation is expected to be designed to include all key components that defines product manufacturing consistency, reliability, product quality, and data accuracy.
The key components in designing a validation should base on scientific knowledge, literature review and data obtained from the pre-clinical studies. The objective of the validation must be clearly defined to enable an effective process validation plan. It should include established measurable product quality indicators such as process parameters, in process QC (e.g. time points and sample sizes) and target product profile (acceptable product outcomes). Standard operating procedure must be developed to outline process to be followed throughout the manufacturing and testing processes. All raw materials including starting biological material specifications must also be established. Critical equipment used must be properly qualified. Tests and assay to be conducted must be validated. The validation should be conducted up to the preparation process of final product intended use. When starting raw material in manufacturing process is biological product, donor quality becomes the significant variable factor, plan should consider minimizing the variability by using repeated donor in multiple processes when possible. Unanticipated outcomes or worst case scenario, when occur, should be carefully documented and analyzed to determine probable causes and resolutions. Repetition of the process is necessary and should base on the analysis of process and data from the preceding validation processes. Raw data must always be included with validation results.
The biological product manufacturing process is complex; the extent of the validation should factor in all elements of product quality attributes and the intended use of the final product. Effective manufacturing process validation should be designed not only to ensure the manufacturing process consistency and reliability but also the highest degree of product quality and integrity of data.
