A Lifecycle Approach to Optimizing Cleaning Systems - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

A Lifecycle Approach to Optimizing Cleaning Systems
Clean-in-place systems should be optimized during design and commissioning and after validation.


Pharmaceutical Technology
Volume 36, Issue 12


(GLOWIMAGES/GETTY IMAGES)
In the 1990s, pharmaceutical manufacturing facilities started to adopt clean-in-place (CIP) technologies to improve cleaning processes and increase critical equipment uptime. While these early systems provided significant benefits over manual cleaning, they were assembled before more modern guidance on construction and optimization. Their designs have subsequently been propagated to other production facilities without significant re-evaluation. As such, cleaning cycles are often an afterthought during current process design and development efforts, resulting in cycles that are poorly conceived, painstakingly long, or unnecessarily wasteful.

Focusing on the cleaning-system design throughout the lifecycle can yield significant cost and time savings for an organization. At the onset of a project, the equipment and piping should be reviewed for sanitary design to facilitate CIP methodology. After the design and build, cleaning cycles should be properly commissioned via testing and analysis. Often, the cleaning systems and cycles are qualified and validated as delivered, thus imposing change control barriers to conducting cleaning cycle optimization. Although the modification of cleaning cycles after validation is more complex, there is a pathway to measured and controlled improvements through mechanical design or automation development. This pathway requires balancing the benefits and desired outcomes of the optimization with the costs and available resources for design and implementation. The following is a brief look at techniques to optimize cleaning cycles throughout the equipment's lifecycle.

Equipment design


Figure 1: An example of flow-path design.
An efficient cleaning cycle begins with equipment designed to ensure successful cleaning. Tank and piping design should be reviewed for sanitary cleanability, as described in section SD-3.1 of the American Society of Mechancial Engineers Bioprocessing Equipment standard (1). This design may include minimizing deadlegs; verifying pipes are sloped toward a drain; checking for low-point drains, sanitary connections, and valves; and verifying that all product-contact surfaces are accessible to cleaning solutions.

The next step in the cleanability review is to create a preliminary design of flow paths for CIP circuits. An example is shown in Figure 1. Segments of equipment and piping should be properly separated and/or combined into different cleaning circuits as part of a preliminary design. Important considerations include process and schedule requirements, potential residues, and piping design.

Process and schedule. Knowledge of the equipment's use can provide insight on process hold or transfer times. Transfer lines and tanks may need to be chained together into a single CIP circuit for quick equipment turnaround to meet these demands. Clean and dirty hold times may also affect equipment scheduling and the cleaning requirements.

Residues. Characterizing residues through cleaning studies and identifying associated product-contact surfaces aid in parameter development. Certain residues may require different cleaning solutions, concentrations, and temperatures for suitable cleaning to occur. This analysis can help organize circuits by common cleaning parameters.

Piping design. Available transfer panel connections may limit the combination of certain transfer lines and tanks. The user should account for line sizes and lengths as major pressure drops may decrease flow and turbulence within the pipe. Additional pumps and other spool pieces may be required within the system. Caution should be exercised in these cases to minimize manual configuration steps and reduce the risk of setup errors. Finally, the user should consider the availability of low-point gravity drains throughout the CIP circuit. Gravity drains remain crucial for efficient CIP cycles.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
31%
Breakthrough designations
8%
Protecting the supply chain
42%
Expedited reviews of drug submissions
8%
More stakeholder involvement
12%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here