Mark Dalziel

Millions of pounds worth of products are at risk if contamination occurs in a cleanroom environment. According to an independent consultant (Cleanroom Management Associates Inc) for our company, contamination from personnel and equipment, such as wheeled carts and tanks, is a major concern in cleanrooms and controlled environments. 

 Mark Dalziel. Managing director at Dycem Ltd

The consequences of contamination are severe. A single microbe in a batch of aseptic drugs could cause the entire batch to be quarantined or scrapped, leading to supply shortages, financial consequences, product recalls, FDA warning letters or even company shutdown in the worst case scenario. 

High levels of air-borne contamination can lead to microbial corruption of cleanroom surfaces. By their very nature, the movement of airborne contaminants is volatile, which makes detection and prevention measures difficult.  Contaminants are generated by people, process, facilities and equipment, and must be continually controlled and removed from the air. 

Particles outside critical areas are a potential problem because they are not easily detectable, particularly small, light, invisible particles. Even loose particles that settle on the floor can be easily crushed into very small particles and redistributed back into the air due to vortices created by movement. These airborne particles become suspended in the air and get carried into the critical area where they present a potential hazard. Such particles are difficult to control because they are hard to see with the naked eye. 

An effective contamination control regime should be put in place. ISO cleanroom standards recommend and cGMP necessitates that the introduction of particles into critical areas is minimised. 

Effective contamination control requires a progressive zonal approach. Areas that are critical to maintaining cleanroom zones are entrances and exits; any areas used or inhabited by personnel, particularly gowning and staff changing areas and airlocks. Organisations also need to monitor and ensure that effective decontamination measures are in place in any areas where equipment, trolleys or tanks are moved. 

All critical areas should also be sampled for particulates.  Particles can be viable or non-viable, made from different materials, come from different places and travel large distances. There are two main types of contamination: 

external—gross atmospheric contamination, which can infiltrate a facility

internal—the human body can generate 5–10 million skin, hair, dirt, and clothing particles every minute.

One of the most effective ways to minimise airborne contamination is to focus on the design of the cleanroom; all processes should be implemented with the reduction of airborne particles in mind. 

Regulators and other professional bodies such as the International Society for Pharmaceutical Engineering (ISPE) recognise the importance of controlling contamination and implementing an effective contamination control flooring system. Flooring used in critical areas can be one of the most effective ways of reducing all contamination whether it’s foot, wheel or airborne, since the majority of contaminants enter the cleanroom at or near floor level. Unprotected flooring enables contaminants to be picked up on shoes and on the wheels of carts where they are tracked into the critical area. Here, there is a risk of them being redistributed back into the atmosphere. 

Specialised flooring solutions can vastly reduce contamination risks. For example, polymeric flooring embeds particulates within its cellular structure, rather than binding it with surface adhesive as is done with peel-off mat flooring products. Peel-off mats have a surface area that is on average five times smaller than polymeric flooring, which doesn’t allow the three full wheel rotations necessary to decontaminate wheeled traffic. In addition, peel-off mats are also prone to wrapping around wheels of trolleys and carts making it impossible to control cross contamination in corridors. 

In general, it’s important to consider the following: 

Space is important. Contamination on feet and wheels come in multiple layers and varying sizes, requiring multiple steps for complete decontamination. Effective decontamination needs at least six footfalls, three for each foot, or three full wheel rotations when using polymeric flooring. Companies that don’t allocate enough space to their cleanroom decontamination zones may be running unnecessary risks that can quickly impact on production and yield.

Permanent solutions offer the most effective controls.  Temporary/peel-off flooring measures that have to be regularly changed cannot combat airborne contamination. As soon as the flooring is lifted to be changed, all the contaminants on the floor will instantly become airborne and this creates a potentially damaging cycle of repeated airborne contamination.

Inadequate cleaning procedures are a common pitfall. Companies should look carefully at ongoing cleaning and maintenance to ensure optimum contamination control measures are in place at all times.

Articles

Millions of pounds worth of products are at risk if contamination occurs in a cleanroom environment. According to an independent consultant (Cleanroom Management Associates Inc) for our company, contamination from personnel and equipment, such as wheeled carts and tanks, is a major concern in cleanrooms and controlled environments.

Contamination: Invisible And Airborne

This article is part of a special feature on cleanrooms that was published in the December issue of PTE Digital.

Contamination in all its forms should be identified and reduced whenever and wherever possible. The best managed cleanrooms/critical environments start at the entrance to the building and implement a holistic contamination control programme, starting with basic entrance matting to reduce the ingress of mud, grit, water and gross contamination, and becoming progressively cleaner as you get nearer to the critical area.  

The specifics of the exact products, processes and protocols required largely depend on the class of cleanroom, number of staff, frequency of cleaning and future company improvement goals; for example, reducing environmental impact. 

Normal solutions comprise some form of workwear, such as a lab coat and work shoes, to a washable or disposable cleanroom suit with facemask, hat, gloves. There will also be one form of contamination control flooring protection system at all entrances and exits to the critical areas, such as airlocks, changing rooms, and transfer hatches. 

When selecting detergents for cleanrooms, it is necessary to rotate the solutions used at regular intervals as germs become more resistant to a specific cleaner. It takes a lot of time and money to validate a new cleaning detergent/product; this is accepted as a necessary investment because if the cleaning solution fails and contamination enters the clean area, the costs can be prohibitive.

To select the right solutions, companies must first consider how clean they need the clean area to be, i.e., what are the allowed viable and non viable counts pass fail rates? 

The cost of cleaning in the cleanroom is always far higher than cleaning 

 the cleanroom; hence everything that can be done to keep the dirt out is highly cost effective, such as the use of polymeric flooring. It is widely accepted that around 80% of all contaminants entering a cleanroom do so through entrances and exits at or near floor height (

Time is also a consideration; one must define how long one cleaning system takes 

 another. Also, how aggressive is the cleaning system? The answer is usually a trade off between killing everything very quickly, and risk ruining other sensitive and even nonsensitive equipment. I have even seen stainless steel eaten away by aggressive cleaning systems so beware! 

Before introducing new protocols, proper validation is vital as the "magic" new solution may not be quite as it first appears! 

All pharmaceutical companies place a great deal of importance on continuous good manufacturing practice (cGMP). In today's world, environmental improvement is a key goal and there is often a lot of wasted electrical energy from using HEPA or UPLA filters to control the class of cleanroom or mini environment. Also, the use of disposable or consumable products when longer term options are readily available simply seems a waste of resources. A couple of obvious examples are the use of disposable Tyvek suits 

 washable, reusable cleanroom clothing, and using peel off sticky mats instead of the environmentally friendly, polymeric contamination control systems. 

The best way of ensuring a long active life of a cleanroom and its equipment is to slightly over engineer the cleanroom and standard operating procedures in the first place so changes and upgrades can easily be accommodated. If this is not done, then companies will be continuously working hard to meet the standards needed, which is going to be both costly and time consuming. 

Contamination in all its forms should be identified and reduced whenever and wherever possible.