Wednesday, September 29, 2010

Oxoid - Assuring Microbiological Control in Pharmaceutical Cleanrooms

Assuring Microbiological Control in Pharmaceutical Cleanrooms

Oxoid provides a wide-range of products for use in assuring microbiological control in the designated cleanroom environments required for aseptic manufacture and processing of sterile pharmaceutical products.

A number of important measures are required to minimise the potential for microbiological contamination in cleanrooms, including:

  • Good cleanroom design
  • Effective air handling
  • Cleaning and disinfection
  • Staff training and adherence to strict aseptic techniques
  • Proper fitting of cleanroom gowns
  • Sterilisation of materials brought into the clean environment
  • Adequate monitoring of controlled conditions, such as air flow and air pressure

In order to ensure that these measures are effective at eliminating risks of microbiological contamination, companies perform investigations, such as aseptic process simulations (or media fill trials) and environmental monitoring. In addition, where contaminants are isolated, it is important for them to be characterised and identified in order to pinpoint the source of contamination and to eliminate it effectively.

Oxoid Products for Media Fill Trials

Media Fill Trials are performed to validate/revalidate the robustness of aseptic manufacturing processes, demonstrating if a product is likely to become contaminated during the filling process. In order for Media Fill Trial data to be meaningful, it is important that the trial simulates the actual filling process as closely as possible. This requires the medium used to be filter sterilised (just as the product would be) prior to filling.

The most commonly used medium for Media Fill Trials is Tryptone Soya Broth (TSB), as recommended in industry guidelines (FDA Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing – current Good manufacturing Practices). Standard TSB products require heating to dissolve (which is time consuming and costly for companies that have this facility) and have poor filterability (causing sterilising filters to block before the end of the run).

Oxoid cold-filterable TSB (cfTSB), on the other hand, is easily dissolved and highly filterable (with a known Vmax for each batch) without the need for heating. This reduces the risk of blocked filters during the process simulation, saving the time and cost of repeat trials. Oxoid cfTSB is irradiated, to eliminate yeasts, moulds, bacteria, bacterial spores and mollicutes (mycoplasmas), ensuring that it is suitable for use in pharmaceutical clean rooms and support areas. For products, such as Oxoid cfTSB, that may contain materials of animal origin. Oxoid provides all the necessary certification and documentation to ensure that these materials meet regulatory requirements. In addition, Oxoid provides a meat-free alternative to cfTSB. Oxoid cold-filterable Vegetable Peptone Broth (cfVPB) is manufactured entirely from meat-free materials. It is a highly nutritious, general purpose medium and comes with similar filterability data and documentation as its TSB equivalent.

Oxoid products for environmental monitoring

Environmental monitoring is used to ensure that required levels of control in the cleanroom are being maintained (and to detect any loss of control, should it occur). Potential routes of contamination include air, environmental surfaces and personnel. The environmental monitoring programme should encompass effective methods for sampling of the environment; and for the growth and isolation of potential contaminants.

Air sampling

Microbiological sampling of air can be passive, using settle plates, or active, using an automatic air sampler.

  • Passive air sampling
    Oxoid Settle Plates can be used to sample the microbiological quality of air by placing them strategically within the test area and leaving them exposed to the air for a set time period (normally 4 hours). They are then incubated under appropriate conditions to confirm the presence of micro-organisms and to ensure that levels of contamination fall within acceptable limits for the cleanroom category. Oxoid 90mm settle plates contain Tryptone Soya Agar (TSA), a general purpose medium, or Sabouraud Dextrose Agar (SDA), ideal for the growth of yeasts and moulds, and are available in a ‘deep fill’ format to avoid desiccation of the medium. The plates are irradiated and triple-wrapped to ensure that they are suitable for taking into pharmaceutical cleanroom areas.
  • Active air sampling
    The Oxoid Air Sampler is an efficient and reliable method for automatically sampling air at a fixed rate of 100 litres per minute. Air is drawn through small holes in the sampling head and directed onto the surface of an agar plate. The agar plate is then removed and incubated in order to assess levels of contamination. The Oxoid Air Sampler can accommodate 55mm and 90mm plates and has flexible plate holders which allow for slight variation in plate diameter. Oxoid provides a full range of suitable pre-poured culture plates for use with the Oxoid Air Sampler, including TSA and SDA in 90mm and 55mm contact plate formats.

Surface sampling

It is important to perform regular sampling of surfaces within the aseptic processing environment, including equipment, walls, floors and counter tops.

Flat surfaces can be sampled easily using Oxoid Contact Plates. These specialised agar plates are manufactured precisely to ensure a smooth, evenly distributed layer of agar on each plate. Sampling is achieved by gently rolling the domed surface of the agar onto the test area. The plate is then incubated under appropriate conditions to obtain colony counts. Oxoid contact plates are available for a range of media, including TSA and SDA, with or without neutralisers to counteract the effect of residual sterilants or cleaning agents that may be on the test surface. In addition, they can be supplied irradiated and triple-wrapped for use in designated clean areas.

In an environmental monitoring programme, it is important to include the sampling of surfaces that are not flat or are difficult to access, as these areas may be more difficult to clean and disinfect. Oxoid provides a range of single tube swab kits for this purpose. Individually triple-wrapped, these swabs are manufactured to the highest quality standards and can be used with confidence in critical areas such as isolators and clean rooms.

Personnel sampling

Periodic sampling of clothing (gowns and gloves) is used to measure the effectiveness of aseptic precautions. Oxoid provides a wide range of products for monitoring personnel. Gloves can be sampled (prior to removing or replacement) by touching all fingers and thumbs onto the surface of an agar plate. Other garments can be sampled using Oxoid Contact Plates or the single tube swab kit.

Oxoid Products for the identification and characterisation of isolates

Identification of isolates is important for locating and addressing the source of a contaminant in pharmaceutical production areas. Identification can be performed manually, by using biochemical identification kits such as the Microbact™ and RapID™
systems, or automatically, using the Dupont Qualicon RiboPrinter® microbial characterisation system available from Oxoid in Europe and Australia.

The Riboprinter provides an automated genetic fingerprint (the RiboPrint™ pattern) for any micro-organism in less than 8 hours. The system requires minimal operator intervention and offers walk-away processing. In addition, unlike alternative methods, the RiboPrinter® system is able to establish different genetic fingerprints for organisms of the same genus and species. This allows laboratories to detect the precise source of contamination and saves valuable time in the investigation of

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