SubscribeA lot of time and money is spent removing contamination within cleanroom environments. But is enough being done to prevent contamination entering the cleanroom in the first place? And would a different procedure necessarily take more time? Karen Rossington, Marketing Manager at Shield Medicare, explains the benefits of sterile multi-pack consumables.
"The transfer of materials into and out of the unit is one of the greatest potential sources of contamination." (MCA Rules & Guidance for Pharmaceutical Manufacturers and Distributors 2002.) The need for better transfer and disinfection procedures has been highlighted by studies looking into the bioburden on a range of items passed into pharmaceutical isolators1.
This work showed that 60% of items ready for transfer were contaminated with bacteria prior to disinfection. More significantly, 40% of items were contaminated with bacterial spores that would not be removed by spraying with alcohol alone.
| Table 1: Sample testing of items routinely used in isolators | ||
| Item | % contaminated | % Bacillus (spores) |
| Syringe package | 60.0 | 40.0 |
| Swab package | 66.7 | 16.6 |
| Needle package | 60.0 | 20.0 |
| Sharps bin | 57.1 | 42.9 |
Everyday cleanroom items pose a contamination threat
Further work was carried out to assess the effectiveness of different liquid disinfection techniques1 (Table 2). Spraying and wiping was found to be the most effective method of transfer disinfection - especially against spores - because bacteria and spores can create a protective biofilm and therefore require the surface to be agitated by wiping to remove them.
| Table 2: Validation of liquid disinfection techniques | |||
| Reduction of organisms | Spray 70% IMS | Wipe 70% IPA | Spray & Wipe |
| S.aureus | 99.8 | 99.6 | 100 |
| B.subtilis | 27.6 | 80.6 | 93.9 |
Reduce initial bioburden
However, even if a pharmaceutical facility adopts good spray and wipe protocols, there are inherent risks of a high initial bioburden from certain types of packaging. For example, with paper-backed items the paper itself is porous so it can readily accept contamination and it presents an uneven surface that makes wiping less effective. In addition, good practice should always try to limit the amount of paper passed into a cleanroom environment.
An effective solution is to use a sterile multi-pack that contains a quantity of sterile components, removing the need for individual packaging. The smooth polythene bag of a sterile multi-pack is easy to wipe and does not support the presence of bacteria in the same way as paper. Multi-packs are double bagged, so that gross contamination can be removed during the first transfer by the removal of the outer bag.
Many components required in the cleanroom are difficult to spray and wipe, due to their small size or awkward shape. Again, the multi-pack bag is easier to wipe effectively.
Reduce packaging waste
Multi-packs eliminate the need for individual packaging and therefore produce significantly less packaging waste. This minimises the space required to store waste items, which can present a problem within the confined space of isolators or laminar flow cabinets. They also minimise environmental impact and can reduce the cost of disposal.
"Individual paper packaging creates a large amount of waste that takes up valuable space in an isolator."
But will it add to the transfer time?
Regulatory authorities are demanding better disinfection procedures, usually leading to additional physical wiping. The time taken to spray and wipe 25 individually packed syringes is significantly greater than the time taken to spray and wipe one polythene multi-pack containing 25 loose syringes. Many controlled areas will require at least two transfers, so that time difference is multiplied.
If you take into account the additional time savings in counting batches, recording batch codes, opening the packaging and disposing of the packaging, then the multi-pack presents an extremely efficient solution. Independent data from a leading commercial aseptic unit recorded an 86% time saving* for transferring 25 syringes 2.
Increase cleanroom capacity
There are other compelling reasons for using sterile multi-packs of components. If you look at the data in Table 3 in another way, it shows you could transfer 7.5 times* the volume of components with no extra staff allowing a significant increase in cleanroom capacity.
Since many cleanrooms are already close to efficient capacity, multi-packs can make a positive contribution to both the output of the facility and the more effective deployment of technicians.
The multi-pack concept
Multi-packs offer an efficient method of high quality transfer of quantities of sterile components into the controlled workspace. The sterile double-bagged packs contain pre-counted sterile components in a range of quantities such as 5, 10, 25 or 50 in order to reduce the risk of any initial bioburden and mean that only one item needs to be disinfected. The single bag is easier to wipe, enabling more effective spray & wipe protocols to be used.
"Klerpack Multi-Packs offer a wide range of components, quantities and packaging options."
Multi-packs should be produced in a cleanroom environment to GMP standards and gamma irradiated to ensure sterility. They should also be CE marked where appropriate.
A wide range of components is available as standard and custom or mixed-pack options can be produced to order. For users of gassing isolators multi-packs can be provided in vaporised hydrogen peroxide packaging to reduce aeration time and decrease production downtime.
Multi-packs are also available in beta bags for direct connection to an isolator port, offering even greater efficiency.
And don't forget the basics!
EU GMP guidelines state that all items passed into a Class A environment must be sterile3. This includes sharps bins, bags, paper (which must be low shedding and free of binders and chemical additives) and pens (which must have alcohol-fast permanent ink and alcohol-fast printing on the barrel, with low sodium content). All these items are now available double bagged and sterile.
Still not sure? Check how good your current transfer techniques are…
A kit is available that can be used to train technicians in correct disinfection procedures and can also be used for ongoing evaluation of techniques and protocols. The Glo-germ Operator Training Kit uses liquid and powder containing particles that fluoresce under UV light. It is designed for use in the training suite, away from production areas.
Simply dust an item (e.g. a paper backed syringe) with the powder, spray and wipe according to your protocol and then place the item under the UV light to see whether any particles remain. If some particles fluoresce, this indicates that if there were real contamination on the item it would not be removed and you might need to look again at your procedures, or consider lower-risk items for transfer, such as sterile multi-packs.
*Note: the time savings obtained with the use of Klerpack Multi-Packs are variable and are dependent on the items, quantities and protocols in use.
References
- "Validation of liquid disinfection techniques for transfer of components into Hospital Pharmacy Cleanrooms". Hospital Pharmacist Sept 2001. M G Cockroft et al.
- Lorna Purdy poster presented at NHS QA Symposium Oct 2001. Comparison of 25 x 50ml syringes in two stage transfer with IPA wipes as individuals or as Klerpack Multi-Packs
- Eudralex. Vol 4 Good Manufacturing Practice, Annexe 1 "Manufacture of Sterile Medicinal Products"
- "Evaluation of the effectiveness of polymeric flooring.." European Journal of Parenteral Sciences 2002. Caroline Clibbon, Research Microbiologist at GlaxoSmithKline