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Suzanne Stubbs
Quality Consultant
Shield Medicare
Farnham
UK
E:[email protected]
This article will look at ways of reducing the initial bioburden on items passed into the cleanroom, so that contamination is minimised. This includes:
- Using the most effective disinfection technique.
- Reducing the number of paper-backed items.
- Reducing the amount of packaging that needs to be disinfected, by bulk packing items such as syringes, needles and waste bags.
- Ensuring the disinfectant used stays sterile and does not cause contamination.
Use of effective disinfection techniques
As the EU GMP Annexe 1 states, “The transfer of materials into and out of the unit is one of the greatest potential sources of contamination.”(1) The need for better transfer disinfection procedures has been highlighted by studies investigating the bioburden on items passed into pharmaceutical isolators.(2) This work showed that approximately 60% of items ready for transfer were contaminated with bacteria before disinfection. More significantly, 40% of items were contaminated with bacterial spores that would not be removed by spraying with alcohol alone (see Table 1).
[[HPE19_table1_33]]
Further work was then carried out to assess the effectiveness of different liquid disinfection techniques.(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 that needs to be removed by wiping so that the disinfectant comes into direct contact with the microorganisms.
Reducing initial bioburden
However, even if a hospital cleanroom adopts good spray-and-wipe protocols, there are risks of high initial bioburden from certain types of packaging. For example, the paper in paper-backed items is porous, so it is easily contaminated, and the uneven surface makes wiping less effective. An effective solution is to use a sterile multipack containing a quantity of sterile components, removing the need for individual packaging. The smooth polythene bag of a sterile multipack is easy to wipe and does not support the presence of bacteria in the same way as paper.
Many components required in the cleanroom are difficult to spray and wipe, due to their small size or awkward shape. Again, the multipack bag is easier to wipe effectively.
Reducing particulates
Paper packaging also needs to be reduced within a cleanroom environment because it carries a high particulate load. The number of particles shed is so great that if you open 50 paper-backed syringes over a dark surface you can easily see the shed particles on the surface. By contrast, the polythene multipack bag virtually eliminates the shedding of particles on opening.
Reducing packaging waste
Multipacks eliminate the need for individual packaging and therefore produce significantly less packaging waste. This minimises the space required to store waste items within the confined space of isolators or laminar flow cabinets.
Does better transfer mean more 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 multipack containing 25 loose syringes. Many controlled areas will require at least two transfers, so the time saving is multiplied.
If you take into account additional time savings in counting batches, recording batch codes, opening the packaging and disposing of the packaging, then the multipack represents an extremely efficient solution. Independent data from a leading commercial aseptic unit recorded an 86% time saving(*) for transferring 25 syringes.(3)
Increase in cleanroom capacity
There are other compelling reasons for using sterile multipacks. The same independent data from the leading commercial aseptic unit mentioned above shows you could transfer 7.5 times(*) the volume of components with no extra staff, allowing a significant increase in cleanroom capacity and more effective deployment of technicians.
The multipack concept
Multipacks offer efficient, high-quality transfer of quantities of sterile components into the controlled workspace. The sterile double-bagged packs contain precounted components in order to reduce the risk of any initial bioburden. Only one item needs to be disinfected, and the single bag is easier to wipe, enabling more effective spray-and-wipe protocols to be used.
Multipacks should be produced in a cleanroom environment to good manufacturing practice (GMP) standards; in addition, they should be gamma-irradiated to ensure sterility. They should also be CE marked where appropriate.
A wide range of components are available as standard, and custom or mixed-pack options can be produced to order. For users of gassing isolators, multipacks can be provided in vaporised hydrogen peroxide packaging, to reduce aeration time and decrease production downtime.
Preventing spore contamination from disinfectants
Maintaining cleanroom integrity also demands the safe delivery of the disinfectant: EU GMP Annexe 1 states: “Disinfectants and detergents used in Grade A and B areas should be sterile prior to use.”(1)
In most cases, disinfectants are delivered by either trigger sprays or aerosols. Trigger spray systems offer significant advantages over aerosols:
- They include an adjustable nozzle so liquid can be dispensed as a jet or a spray.
- They are environmentally friendly, as they contain no propellants requiring special disposal procedures.
- All of the liquid can be dispensed from a trigger spray, so there is no wastage.
However, there is a significant potential drawback with some trigger sprays, as contaminated air can be drawn back into the bottle so that the liquid is no longer sterile. Validation work in the licensed pharmacy unit of the Queen Elizabeth Hospital in Birmingham (UK) identified that a trigger spray alcohol had been contaminated with fungal spores only eight hours after opening.(4)
A new trigger spray system solves this problem, providing the benefits of a trigger spray while guaranteeing the integrity of the contents. The new design operates as a closed system, preventing air from being drawn back into the bottle and so eliminating the possible chance of liquid contamination.
(*)Note: the time savings obtained with the use of multipacks are variable and are dependent on the items, quantities and protocols in use.
References
- Euraldex. Vol 4. Good Manufacturing Practice, Annexe 1. Manufacture of Sterile Medicinal Products Rev 2003.
- Cockroft MG, Hepworth D, Rhodes JC, et al. Validation of liquid disinfection techniques for transfer of components into hospital pharmacy clean rooms. Hosp Pharm 2001;8:226-32.
- Purdy L. Comparison of 25 x 50ml syringes in two-stage transfer with IPA wipes as individuals or as Klerpack Multi-Packs. Poster, NHS QA Symposium, 2001.
- Salvage B. Contamination control at your fingertips. Pharmaceutical Manufacturing International, 1999.
