Cleaning Validation Support
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The project aimed to provide continuous technical support for cleaning validation activities at Takeda's biopharmaceutical manufacturing site in Rieti, Italy. The consultant's role involved drafting validation documentation and managing on-the-floor activities, while also applying a risk-based approach to ensure compliance with global guidelines. Both client and personal goals were achieved, leading to a renewed project and an expansion associated with cleaning validation activities.
Cleaning Validation Support
- 1. Cleaning Validation Support Takeda Manufacturing Spa (Rieti) Nunziangelo Ventricelli – Consultant&Engineer for Altran Spa (EILIS)
- 2. Aim of the project was to supply a continuous technical support for Cleaning Validation activities within the related department in Takeda’s manufacturing site at Rieti (Italy). The duration of the project (1 year foreseen) was extremely connected to the satisfaction of client’s expectations (see also slide n°4).
- 3. Client Background Takeda’s manufacturing site at Rieti is a FDA approved biopharmaceutical company specialized for the production of human plasma derivates. The manufacturing process includes to initially thaw crude plasma in order to obtain, through different process phases, the final Drug Substance that is finally stored as concentrated bulk. The DS is send to other manufacturing sites for further operations. Different equipment and methods such as tanks, centrifuges, ultrafilters, chromatography, filter pressers are adopted within manufacturing site. Personal Background My technical background completely fits the needs of Takeda’s company. In fact, my previous experiences in Cleaning Validation and in Biopharmaceutical Industry were a strong driver for the final choosing of my job profile on this project.
- 4. Client Goals The expectations/goals of the client were to receive a continuous technical support for cleaning validation activities. These were mainly related to the drafting of validation documentation and managing of the on-the-floor activities. Another important expectation of the client was to continuously receive from the consultant, in a proactive way, a different point of view for the approach to validation, and GMP, generally, activities. Personal Goals My personal goals were mainly attributable to improve technical features, specifically, related to cleaning validation area. Takeda’s Rieti plant, in fact, represents a unique company in the global pharmaceutical scenario for the type of products manufactured.
- 5. PRINCIPLES: What does it mean Cleaning Validation? All the activities that aim to demonstrate, with documented evidence, that the approved cleaning process (automatized, semi- automatized, manual) are able to remove products and cleaning agents with efficacy, reproducibility and consistency. All the analytical methods and the acceptance criteria adopted have to be selected on the basis of appropriate scientific rationales. SCIENTIFIC RATIONALES: These two words are the key words to manage cleaning validation activities. The scientific rationales are built up on the basis of the following approaches: RISK MANAGEMENT and COMPANY’s EXPERIENCE/KNWOLEDGE. RISK MANAGEMENT: Within Takeda’s manufacturing site, the risks associated to cleaning validation are addressed and mitigated using a risk based approach. This approach is defined considering the most important global guidelines (ICH , Annex 15, PICs) for the entire workflow. For example: the acceptance criteria to be adopted for cleaning validation are set on the basis of chronic toxicity principles such as the Permitted Daily Exposure approach “PDE”, which considers the potential toxicity effect of products and/or cleaning agents when injected in human patients for his entire life. COMPANY’s EXPERIENCE/KNOWLEDGE: Takeda’s manufacturing site at Rieti is a company specialized in plasma derivates production. related to Cleaning Validation. Plasma derivates are considered endogenous product of human organism. Arguments like this, in association with a good knowledge of product itself and manufacturing process, are kept into consideration for the definition of activities and scientific rationales
- 6. CV Process Workflow & Documentation STEP 1 Preliminary/Study Phase During this phase, on the basis of the equipment to be cleaned (it use, design, role/position within the manfacturing process) a potential cleaning procedure is individuated by engineering department. The Cleaning Validation Study Protocol is the reference document for the management of activities aimed to obtain the first explorative data on the efficacy, reproducibility and consistency of cleaning process previously individuated. Within this document the analytical methods, the acceptance criteria and the number of cleaning runs are also defined. STEP 2 Preliminary/Study Phase Explorative data are collected and analysed within a Study Report. On the basis of data obtained, the potential cleaning process should become or not the main candidate to be validated. In case of the cleaning process is not able to demonstrate efficacy, reproducibility and/or consistency, adjustements to this cleaning process and/or alternative cleaning processes could be proposed and newly preliminary studies could performed. STEP 3 Risk Assessment Phase During this phase, a Cleaning Validation Risk Assessment is written. This is considered a driver document, a reference for the analysis and mitigation of the risks associated to cleaning process. Appropriate scientific rationales are supplied in order to individuate CPPs and CQAs (acceptance criteria included) and how they are addressed. Cleaning validation runs to be performed and Dirty and Clean Hold Times to be challenged are also individuated. STEP 4 Validation Phase On the basis of RA guidelines, the following validation protocols, to manage CV activities (sampling plan, analytical methods), are written: • Validation Protocol for the management of cleaning procedure and Dirty Hold Time validation; • Validation Protocol for the management of Clean Hold Time validation. STEP 5 Final Phase All the CV data (analytical data, Dirty and Clean Hold Time challenged, samplings, potenital deviations occurred) are collected and analysed within Final Reports in order to demonstrate and confirm the efficacy, reproducibility and consistency of cleaning proces.
- 7. OVERALL PERFORMANCE CLIENT’S GOALS/EXPECTATIONS: All the goals/expectations of the client were achieved. All the cleaning activities were completed on time and assuring a high quality level. Furthermore, concurrently with the routine activities, in collaboration with the client, a deep review of Risk Assessment approach and documents wording were executed. PERSONAL GOALS/EXPECTATIONS: All my goals/expectations were completely satisfied. I improved my technical skills for Cleaning Validation by studying a new risk-based approach since Takeda’s manufacturing site at Rieti represents a unique site in global GMP pharmaceutical industry. The project was renewed several times for the Cleaning Validation Support project (total duration: 1 year). Furthermore, a new project, associated to Cleaning Validation activities for Rieti’s manufacturing site expansion, with a different business model, was assigned to Altran spa. My personal technical portfolio had been enriched thanks to this project experience EFFECT EFFECT