12/21/2010

Clean-in-place Automation: Ensuring Efficient and Effective Cleaning Validation

By: Piyush Dewangan

Pharmaceutical manufacturing facilities are moving towards multi-purpose facilities, capable of producing
diversified range of products instead of having dedicated product lines. This results in smaller batch sizes and
increased changeover requirements. The manual procedure is time consuming and poses a major challenge in
reducing the batch cycle time. The cleaning cycle time, which generally ranges between 30-40 percent of the
processing time and sometimes more than 50 percent of the total processing time, adds additional challenges besides
others, such as maintaining quality and adhering to regulatory compliances. Thorough cleaning is of paramount
importance to eliminate cross-contamination and ensure quality of the drug products. Automation of cleaning
process helps pharmaceutical companies to overcome such challenges.

Clean-in-place (CIP) automation systems are available as either a semi-automatic or a fully automatic system with
programmable logic controller (PLC). The system consists of multiple balance tanks, sensors, valves, heat
exchangers, chemical feed equipment, spray nozzles, data acquisition systems, and such others. A well designed
CIP system helps in minimizing the cleaning cycle time while ensuring significant improvement in the cleanliness
and hygiene of equipment.

The performance of cleaning activities largely depends on measuring and controlling the critical parameters. It is
important for a plant manager to use appropriate amounts and type of chemicals, and ensure that those chemicals are
removed completely before the next processing to prevent contamination. Contamination can be with active
ingredients, unintended materials or compounds, or it could be microbiological contamination. Inappropriate
cleaning or failure to prevent cross-contamination or adulteration may cause serious problems, which can harm the
subsequent batches of pharmaceutical products in terms of safety, efficacy, quality, and other parameters.
Additionally, ineffective cleaning may result in scraping expensive materials as waste and result in regulatory
action. In case of equipments that require microbiological cleaning, a sterilizing-in-place (SIP) cleaning process is
required for sanitizing or sterilizing them.

The cleaning process automation with clean-in-place (CIP) technology enables tracking of all cleaning procedures,
helps in maintaining highly hygienic conditions, and ensures repeatability of processes. The CIP cleaning process
involves multiple rinses with water, weak acids, weak bases, various detergents, and other cleaning agents. An
automated CIP technology facilitates cleaning interior surfaces of pipes, vessels, process equipment, filters, and such
other equipments without disassembling. It helps in reducing the downtime between product run and changeovers,
and facilitates improved safety and repeatability with reduced human error. A well-designed automatic CIP system
is permanently fitted with several cleaning equipments. This facilitates reduced waste time, efforts, damages,
deterioration due to transportation, and handling of equipments prevalent in case of manual cleaning system.

Automating the cleaning process enhances the effectiveness of cleaning with automatic and controlled supply of
cleaning solutions, detergents, and water. This enables appropriate balance in terms of time, temperature,
concentration, pressure, and hydraulics which results in improved cleaning performance. Sometimes increase in
temperature can enhance the effectiveness of the cleaning process, which is normally achieved by applying thermal
energy of cleaning solutions, and chemical energy of detergent or solvent used. The objective is to maximize safety
by eliminating cross-contamination, minimizing cleaning cycle time, reducing changeovers, and such others. It not
only increases the plant utilization, but also results in significant savings due to reduced labor-hours, recycling of
cleaning agents, and increased environmental protection. The automatic clean-in-place system facilitates easy and
successful cleaning validation by satisfying several validation parameters, such as proper cleaning process,
equipment, cleaning agent, cleaning techniques, number of cleaning cycles, time frame for validation, and others for
ensuring regulatory compliance.

ARC welcomes your opinions regarding clean-in-place system deployment, its usefulness, limitations, and such
others that could host further discussion on this topic. Please write to pdewangan@arcweb.com.