Cleaning specification, no doubt, is bound and defined in parity with the application, location and organization. However, it turns critical when it is outcome-oriented, especially in the pharma segment, requiring cleaning validation during preparation, processing and post production stages. Clean India Journal takes a peek into this specialized cleaning procedure.
IN PHARMA production, cleaning procedures are critical in order to maintain safety and quality of products. Cleaning, in general, addresses the overall hygiene but it turns critical when the hygiene levels are defined, parameters set, procedures defined and finally tested for validation certification.
“Critical cleaning is an indispensable practice in crucial manufacturing premises like pharmaceutical drugs and formulations to ensure best in class product quality,” says Prashant Nagre, CEO, Fermenta Biotech Limited. “In pharmaceutical processing units, several factors are responsible for contamination at various stages, which can be attributed to air quality, installed equipment, movement of workers and quality of raw material. However, it is the finished product quality that matters most in drug production, as contamination at terminal stage of processing cannot be reversed.”
More of a closed room area, all surfaces of the production and product storage have different cleaning requirements and standards to meet. The manufacturing equipment goes through cleaning before and after every batch of production to protect product purity. The cleaning is critical as the processes are determined on the analysis of the residue on the manufacturing equipment. Hence, the cleaning methodologies are developed to detect and treat the target residue and the other surrounding product surfaces. Apart from the procedures, the cleaning agents are specified to ensure the residue is removed from the surfaces.
The process also engages cleaning agents requiring further analysis of the chemical residue. “Some of the typical critical cleaning laboratory setups include class clean rooms, chemical and alcohol based cleaners like IPA and benzalkonium chloride, antibacterial liquid sanitizers to reduce surface microbial load, air lock doors and air flow vent for air-borne microbes,” explains Nagre.
Aqueous cleaning is one method of critical cleaning. Generally, aqueous cleaner formulations use key ingredients such as surface active agents (surfactants) that are excellent wetting agents. These agents allow the cleaning solution to penetrate into crevices while getting under soils to enable removal. This highly dilute solution removes even stubborn substances from hard surfaces, including stainless steel, glass or plastic.
Different types of residues are best cleaned by either an alkaline or acidic cleaner. Alkaline cleaners are used on oily residues and acidic cleaners are used on inorganic residues. Formulated cleaners with wetting agents, emulsifiers, dispersants, chelating agents and anti-redeposition agents give the most robust residue removal.
Understanding the properties of both the residue and the hard surface are important and can be used beneficially to improve the aqueous cleaning process, according to a white paper released by Alconox, USA. By understanding the structure, functional groups, molecular polarity, solubility and molecular weight of the residue being removed, it is possible to determine if an alkaline or acidic cleaner would work best for a given cleaning method. In most cases, simply by choosing the correct acidic or alkaline pH range for the type of residue being removed, you will be able to select the correct type of cleaner.
Generally, alkaline cleaners are used on oily residues and acidic cleaners are used on inorganic residues. Cleaners are intended for manual/ultrasonic cleaning, or machine/spray CIP cleaning in either powders or liquids and with or without phosphates.
[box type=”shadow” ]The Pharma industry is open to newer cleaning solutions. Besides chemicals, there are no specific cleaning equipment for critical cleaning. Nonetheless, battery operated machines are much preferred. The new machines that we see at the exhibition if suitable are tried, tested and validated before being adopted for cleaning.
– Arvind Babu
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“Other sensitive installations in pharmaceutical sector consist of dedicated aircon systems for various zones equipped with pressure differential regime to prevent air borne cross contamination as well as floor, surface and wall cleaning systems. A foolproof laboratory also needs a rigorous and validated scheduled cleaning system to avoid any contamination occurring from neglected areas such as AHU internals to stop contamination, as condensate water and dust from AHU drain may lead to fungus formation. Use of proper fungicides is must. Similarly, cleaning of duct with adequate devices is required on regular basis to maintain hygienic environment,” adds Nagre.
Besides, the manufacturing equipment, Michael Lehtinen, Global Product Manager, Chromatography Consumables and Speciality Products at Thermo Fisher Scientific, in his article states that sample tubes, containers and associated closures are not necessarily high value products but what they contain is. “Consequently, ensuring these are as clean as the processes and environments in which they are used requires the understanding and adoption of proven methods to guarantee essential GMP quality assurance and traceability. An in-depth appreciation of the applications for which the containers will be used is, therefore, necessary to ensure that the best cleaning process is implemented, while keeping costs to a minimum. There are a variety of container-cleaning methodologies available, all designed to meet different cleaning requirements these include: surface modification, via silanization or siliconization, depyrogenation, sterilization and low particulate cleaning.
“Knowledge of appropriate safety and regulatory requirements is also essential, not only for current regulations, but also how they may change in the future. The pharmaceutical industry requires a wide selection of chemicals and processes to achieve better contamination control at lower costs. However, health and environmental concerns have resulted in restrictions on the use of certain chemicals and processes. To foresee future trends, an understanding of how the approaches of regulatory agencies may change over time is advantageous.”
The entire cleaning process requires professional and trained manpower. Micheal Lehtinen has suggested in his article that outsourcing such services is cost effective. He states, “It is evident that cleaning newly manufactured drug product containers to appropriate specifications is a costly process in terms of time, resources and in-house expertise. Consequently, this task has increasingly been outsourced during the last three to five years. Since outsourcing companies have the expertise to ensure that all containers are compliant with various regulations, such as those from the FDA and US Pharmacopeia (USP), in-house expertise is no longer essential. Costs can, therefore, be saved on training and laboratory researchers are freed to focus on product development.
“Outsourcing to a reputable company can significantly decrease the amount of in-house compliance work that need be undertaken. If the outsourced company can offer ‘cradle to grave’ traceability through batch record tracking, this ensures that, should the FDA have any questions at any time, the necessary paperwork will always be available to provide an immediate answer. In addition, manufacturing processes and cleanroom facilities that ensure products are handled in Class 100/10 environments can only further secure product quality.”
To sum up, outsourcing of custom cleaning and packaging, therefore, has some clear advantages for the pharmaceutical industry – Access to critical cleaning expertise; Production of containers to exacting regulatory specifications is not a distraction from the company’s product expertise; Economy of scale; Accommodation of flexible demands and customization for new applications and Testing, full documentation and ‘cradle to grave’ traceability.
However, India, says Arvind Babu, Director-FM, Travel & Hospitality, Dr Reddy’s Laboratories, does not have the skilled or trained manpower to outsource. “Critical Cleaning involves specialized processes and the pharma companies have trained in-house manpower to carry of the activities. Quite rightly, selecting a contract cleaning services company that can provide flexibility, confidence and efficiency is no mean feat and there are many considerations to take into account.” Hence, outsourcing such technical services seems far-fetched.
“In fact, critical cleaning being an outcome oriented process which involves not only the equipment and the people in the production but entire environment in the closed room or the clean room setting. To ensure pre-production, production and post-production cleaning are done as required requires corporate level training. This activity can be outsourced or can be done in-done but by a trained and professional team only. Workforce engaged in regular cleaning cannot be put into critical cleaning. There are procedures involved, right chemical dilution to following SOPs which varies from place to place and batch to batch in the production requiring trained and validated efforts,” explains Arvind Babu.
As Micheal puts it, even though the facility head looks for the required expertise, capabilities and services in a service provider, the shortlisting of the company to be engaged ultimately depends on “the bottom line – and potential for savings that can be demonstrated by such a company” which influences the decision making process.
“Outsourcing an expert critical cleaning company can certainly deliver return on investment (ROI). Indeed, value is added since most discovered compounds do not make it to commercialization. This is because internal resources only have an ROI if the product is a success; the truth is that fewer than one in 10,000 are successful.”