Controlled Access. Restriction lift date: 2033-09-30
Investigation of a process analytical technology (PAT) for rapid cleaning verification in the pharmaceutical industry to reduce product changeover time
University College Cork
Within the pharmaceutical industry, it is a regulatory requirement that the equipment's cleanliness must be verified prior to use in order to avoid contaminated or adulterated products. Currently, the techniques used for cleaning verification are extremely variable as the sampling technique categorically relies on human performance. The most commonly used technique for cleaning verification is known as swab and rinse. These techniques are based on the assumption that the contamination is completely removed from the surface during sampling while there is no direct measurement system in place to ensure that 100% of the contamination is removed. This assumption could produce extremely misleading results and ultimately could put patient's lives at risk. This has been proved by the FDA’s recent citation where it said, most of the drug manufacturing-related problems leading to product recalls and manufacturing disruption are caused by cross-contamination. Another immense drawback of the current technique is that it may take up to 3 weeks to complete the verification study, and during this time, the manufacturing equipment is not in use. In addition to this downtime, another major drawback of the current method is the poor swab recovery which may lead to an ambiguous result. Therefore, the pharma regulators are encouraging to develop and use of more science-based analytical tools, and the pharma industries are searching hard for a better alternative. This project was initiated to use a scientifically sound hand-held analytical tool to validate/verify equipment cleanliness in real-time without sampling and laboratory testing. A Specular-Reflectance Fourier Transform Infrared Spectroscopy (SRFTIR) was identified to investigate the capability to detect and quantify surface contamination and produce the result instantaneously & eliminate human error. It is anticipated that this project will deliver a significant reduction in cleaning time which will affect the entire pharmaceutical industry within Ireland and worldwide. Currently, the most commonly used analytical method for cleaning verification in the pharmaceutical industry is swab and rinse testing. These methods are also known as indirect methods, which require extracting contaminants from the surface of the manufacturing equipment. These methods are extremely inefficient and require strong technical and analytical skills to perform. In the Pfizer tablet manufacturing plant, an assessment was performed to calculate the time required to verify the equipment cleanliness, and it was found that completing a cleaning verification study for an equipment train with 10 swab samples will require approximately working 52 hours of laboratory testing. Further assessment was performed in Pfizer large molecule site; they found it required 1-3 weeks to perform the cleaning verification study, depending on the nature of the contaminant. For multi-product facilities, the equipment downtime is a huge forfeiture for the business; ultimately, all of this cost is added up to the final price of the drug/s. The average equipment downtime for Pfizer multi-product facilities is 30% of the total manufacturing time. In addition, there is a great variation in the swabbing technique and recovery. The introduction of an innovative approach to reduce error and improve the consistency of the sampling would be a significant development in the field of cleaning validation and verification for the pharmaceutical industry.
Process analytical technology (PAT) , Cleaning verification , FTIR , Cleaning validation , Changeover time , Real time measurements , Regulatory compliance
Sarwar, A. 2023. Investigation of a process analytical technology (PAT) for rapid cleaning verification in the pharmaceutical industry to reduce product changeover time. PhD Thesis, University College Cork.