SEPTEMBER 20239TECH OUTLOOKacceptance criteria and a `three-run' process validation approach. This being typical across the industry. Because of this traditional approach, the industry also struggled over how to set the required predetermined acceptance criteria. This process validation approach was adopted without ever asking if three cleaning validation runs and predetermined acceptance criteria were appropriate for the validation activity. Based on this reasoning, Annex 15 (section 10) came into existence stating:"The cleaning procedure should be evaluated an appropriate number of times (based on a risk assessment) and meet the acceptance criteria to prove that the cleaning procedure is validated." The cleaning of manufacturing equipment to prevent cross contamination of pharmaceutical products is a fundamental aspect of GMPs. Validations of these cleaning procedures has been required within cGMP for as long as I can remember and is recognized as an important activity to establish that product cross contamination is controlled to ensure patient safety and product quality. While the actual act of `cleaning' is a relatively simple process, the pressures of inspection and scrutiny by regulators have transformed these activities into a complex, expensive, and time-consuming process. I personally have experienced projects consisting of multiple products, multiple pieces of equipment, and multiple cleaning procedures which extended out into years.Like always, companies seek to gain efficiencies and cost savings. Thus, many companies have made various efforts to reduce cleaning activities, such as dedicating equipment or converting to disposable items. However, these strategies have their own inefficiencies and costs. Companies have also resorted to strategies such as product grouping, equipment grouping, matrixing, and bracketing to reduce the amount of cleaning they validate, sometimes without acceptable justification. Many companies today validate the cleaning of only one or two `hardest-to-clean' products, selecting them based on the solubility of the API or because the calculated limit is lowest, even though these may not be truly justifiable criteria. The EU guideline `Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use,' Annex 15 outlines in Section 10 the following:`For a worst-case product approach, a scientific rationale should be provided.' Since 2001, there have been many new concepts introduced due to high expectations by regulators. Examples include:· GMPs for the 21st Century· Quality by design (QbD)· Process analytical technology (PAT) · FDA 2011 guideline on process validation.Globally, the new International Conference on Harmonisation's guidelines (ICH), in particular Q8 and Q9, are some of the major forces driving change in the industry. Movements within pharmaceutical manufacturing itself have seen the rise of:· lean manufacturing· Six Sigma· operational excellence (OpEx)To this end, cleaning validation are based on science, risk, and statistics. It offers a clear direction of making sensible changes and decisions with the cleaning process, that would reduce the complexity, lower the costs, and shorten the process while providing a high probability that the cleaning of manufacturing equipment has been effective. By implementing a truly science-based approach, such as the use of appropriate risk assessments, a streamlined cleaning program may be readily developed that ensures patient safety and product quality while lightening the regulatory burden on industries.Like I keep telling my fellow work colleagues, we learn something new every day. Robert Zanon
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