Reducing risks from everyday items

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 But there is often a range of items that get overlooked, and pass unsterilised into the cleanroom or critical area, posing a contamination threat.

This article identifies such items and suggests techniques for minimising the contamination risks. Technicians are aware of the need for items, such as syringes and needles, to be supplied sterile, and to remove any surface contamination before passing such objects into the cleanroom. Ideally, all items passed into a Grade A or B environment should be either irradiated, autoclaved or gas sterilised to ensure sterility.

Unsuitable packaging However, there are many commonly used items that are often not supplied sterile or suitably packaged for the cleanroom, which need extra consideration. Typical items transferred on a daily basis include: microbiology plates, IPA bottles, wipes, IPA holders, disinfectant sachets, microbiology swabs, micro plate labels, laminated A4 sheets, pens, pressure gauges, rulers, goggles, timers, calculators, syringes, vials, trays and isolator gauntlets. The need for better transfer disinfection procedures has been highlighted by studies investigating the bioburden of items passed into pharmaceutical isolators.² This work revealed that up to 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 (see table 1). Work was carried out to assess the effectiveness of different liquid disinfection techniques² (see 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 which requires the disinfectant to come into direct contact with the micro-organisms, making wiping the most viable option.

No short cuts It is essential that the disinfection procedure is effective for every single item, otherwise the entire exercise is pointless. Technicians need to be trained in the correct techniques and to pay particular attention to the disinfection of items, such as vials of drugs, especially where cytotoxic residues must also be considered. Although shown to be the most effective method, spraying and wiping can be a time-consuming and tedious aspect of aseptic production. However, there can be no short cuts or the integrity of the unit will be compromised. Strips of syringes and needles are often wiped quickly on each side, but ought to be separated into individual items and wiped thoroughly, including underneath the opening, for the procedure to be effective. An efficient solution is to use a sterile multi-pack that contains a quantity of sterile components, removing the need to spray and wipe individual items. Sterile multi-packs containing quantities of common cleanroom components, such as marker pens, cleanroom paper, sharps bins, polyethylene bags, syringes, needles, syringe caps, chemo dispense pins, reconstitution devices, intermittent injection ports, additive caps, fluid dispense connectors, combi stoppers, transfer devices, chemotherapy spill mats and disposable aprons are available. The double-bagged format is also compatible with transfer protocols. 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, meaning that it is easily contaminated with bacteria or spores, while the uneven surface makes wiping less effective. Coupled with the fact that alcohol does not kill spores, paper packaging poses a significant contamination threat.

High particulate load The solution is to select items with cleanroom compatible polyethylene packaging wherever possible. The smooth surface is easy to wipe and does not support the presence of bacteria or spores in the same way as paper. 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 50 paper-backed syringes are opened over a dark surface the shed particles are easily visibble on the surface. By contrast, polyethylene packaging virtually eliminates the shedding of particles on opening. Research has recently been carried out to measure particulates generated by paper-wrapped syringes and needles. The syringes and needles exceeded GMP limits for both 0.5µm and 5µm particles in a Grade A environment on all samples, and in some instances the 0.5µm particles exceeded the guidelines by tenfold. Suggested solutions that will reduce the potential for contamination when using many everyday cleanroom items are given in table 3.