Performance of Cleanroom Garment Fabrics When Processed in an Industrial Laundry, Comparing Irradiation and Autoclave Sterilisation

EU GMP Annex 1 requires that “reusable garments should be replaced based at a set frequency determined by qualification, or if damage is identified.” [1] In the UK, most cleanroom garments supplied to the pharmaceutical and healthcare sectors are washed and sterilised by gamma irradiation. This study compares cleanroom garment fabric performance across the lifespan of multiple fabrics. Previous research has shown that cleanroom garment fabrics terminally sterilised by gamma irradiation remain suitable for use for up to 50 processes, however, these studies often focus on a limited number of samples. This study uses a large sample set, analysing the performance up to 100 processes and compares the performance effects of gamma irradiation vs autoclaving, as an alternative sterilisation method. Multiple market leading cleanroom garment fabrics were washed and dried using a standard industrial cleanroom laundry process and sterilised by either gamma irradiation or autoclave. They were tested for particle barrier efficiency, abrasion resistance, pore size, and tensile strength as new, then at set process counts throughout their life, 10, 20, 30, 50, 70 and 100 processes. A process is equal to one wash/dry/sterilisation cycle. The results show that not all cleanroom garment fabrics deteriorate equally and that some market leading fabrics may not provide adequate performance throughout life, even if they are suitable when new. They also show that autoclaving is comparable with irradiation in durability and performance over a fabric’s life, in some cases performing better than irradiation above process counts of 50.

End-to-end qualification of ready-to-use (RTU) product containers in packaging suitable for No-Touch Transfer (NTT) into Grade A filling zones

No-Touch Transfer (NTT) of pre-sterilised ready-to-use (RTU) containers is an alternative methodology that follows Good Manufacturing Practice (GMP) and Quality Risk Management (QRM) principles. NTT de-bagging ejects contents from secondary bag packaging without direct contact with contents or exposure to an environment that is a lower grade than the zone being entered. The pre-sterilised containers and sterile barriers offer assured sterility at manufacture and are qualified to remain sterile through the supply chain and the stepwise NTT de-bagging process. This eliminates the requirement for in-process material disinfection steps for transfer into Grade A environments. The present article focuses on design qualification of pre-sterilised RTU container packaging, including definition of sterile barriers together with bioburden study data through the supply chain and simulated NTT. It completes a series of EJPPS articles to support peer-reviewed references on NTT. Together, these articles can be defined as end-to-end qualification of the NTT process, demonstrating a high level of assurance that sterility is maintained from manufacture to point of use. Key Words: Aseptic processing, Design qualification, Good Manufacturing Practice (GMP), Life cycle, No-Touch Transfer (NTT), Pharmaceutical packaging, Pre-sterilised containers, Qualification, Quality by Design (QbD), Quality Risk Management (QRM), Ready-to-use (RTU), Supply chain

Recommendations of scientifically sound and appropriate sampling plans for parenteral drug products

This paper gives recommendations for defining sampling plans/sizes that are statistically justified or based on published guidance for typical parenteral drug products Simple tables based on the ANSI/ASQ Z1.4 acceptance sample plans or other published guidance have been collated to aid organisations in selection of appropriate sample sizes/plans for routine drug product manufacture. Key Words: USP <1790>, visual inspection, AQL, power, sample size

Microbial Air Samplers for Meaningful Cleanroom Environmental Monitoring

Airborne microbiological concentrations within pharmaceutical cleanrooms are determined by sampling and to maximise the detection of any airborne microbes, it is essential that the sampling is undertaken in locations where there is greatest contamination risk using air samplers that have a verified and appropriate performance. Sampler performance can be assessed by review of both the physical and biological collection efficiencies that are determined by testing. The physical collection efficiency is the ability to collect particles of various sizes and the biological collection efficiency assesses the collection of viable microbes that includes the losses caused by the physical collection efficiency and the detrimental effect that the sampling has on the viability of the captured microbes. Due to the limitations of the established biological collection efficiency test method, this efficiency is only determined for microbes of sub-micron size which are not representative of the larger microbe-carrying particles typically present with cleanrooms. Samplers with a low physical collection efficiency for sub-micron particles are likely to have a poor performance when this test method is utilised and in an attempt to remove this bias from the testing the ‘biological efficiency’, is often reported. This is a measure of the likelihood that any captured microbes would survive, but is often mistaken for the biological collection efficiency and samplers may be utilised in the false belief that they have an appropriate performance. This article provides information regarding air sampler performance testing and reviews the test results reported by the same independent specialist testing company, therefore negating issues resulting from different testing methods, for three different air samplers. The results that are used to determine the ‘biological efficiency’ are examined to provide information relating to the biological collection efficiency of each sampler and to also provide additional information relating to the physical collection efficiency. Improvements to enhance the air sampler testing procedures, to enable a better direct comparison of the performance of different samplers, are suggested.

A Comparison of the Bacterial Contamination of the Surface of Cleanroom Operators’ Garments following Donning with and without Gloves

Background Specialist cleanroom garments are a potential vector for transmission of microorganisms within these facilities. In order to maintain the low bioburden of such clothing it has been perceived best practice for operators to dress wearing sterile cleanroom gloves. However, the efficacy of such glove use upon the resultant bacterial contamination of the surface of cleanroom garments has not previously been evaluated. Aim To compare surface bacterial contamination of cleanroom garments following their donning by operators dressing with or without gloves. Methods Following prior handwashing and systematic donning of cleanroom clothing by operators dressing wearing either no gloves, non-sterile nitrile gloves or sterile cleanroom latex gloves, a direct agar contact method was immediately undertaken to test garment surfaces at 7 specific sites. Following incubation bacterial levels were suitably quantified. Findings Comparing levels of growth displayed on plates used to test the surface of cleanroom garments worn by operators dressing with no gloves, non–sterile gloves or sterile cleanroom gloves, no significant difference was observed between the percentage of contact plates displaying growth and the levels of growth observed on plates, from any of the sites tested. Conclusion Omission of gloves in line with a systematic handwashing procedure prior to the cleanroom garment donning process, may result in modest economic and environmental gain coupled with a slightly less burdensome procedure. However, this is reliant on rigorous adherence to handwashing protocol and assessment of associated risk factors.

Comparative Evaluation of Amorphous Polymers in Solubility and Bioavailability Enhancement of Famotidine Through Solid Dispersion

The present study aimed to enhance the dissolution rate, therefore bioavailability, of famotidine (FMT) using its solid dispersions (SDs) with polyvinyl pyrrolidone (PVP)-K 30, milk powder, and inulin, both in-vitro and in-vivo. The study was also aimed to compare the effect of different amorphous polymers in enhancing the dissolution rate of FMT. The SDs were prepared with a 1:4 weight ratio by a solvent evaporation technique. Evaluation of the properties of the SDs was performed using dissolution, Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) studies. The SDs of FMT exhibited an enhanced dissolution rate. The FTIR spectroscopic studies showed the stability of FMT and the absence of well-defined drug excipient interaction. The XRD studies indicated the amorphous state of FMT in SDs. The drug release rate of all SDs formulation was found to be greater than the pure drug. Within one hour of dissolution studies, 99.43%, 92.5%, and 58.93% drug release were obtained, respectively, for PVP K-30, milk powder, and inulin. The first two were showing significantly higher release. SDs were also studied for bioavailability studies in-vivo in rats, which confirms that the SDs prepared by PVP K-30 and milk powder significantly enhancing the bioavailability of FMT. The maximum concentration of 15.05±2.45 μg/ml was achieved in 2 hours, and the area under the curve was found to be 33.78±7.3 μg. hour/ml. Therefore, the study results conclude that SDs of the FMT prepared by PVP K-30 successfully increases the dissolution and in-vivo bioavailability. Keywords – Solid dispersion, Second generation solid dispersions, Famotidine, In-vivo bioavailability, amorphous polymers, dissolution enhancement, solubility enhancement.

Insight into the New EU GMP Annex 1

The 2020 release of the EU GMP Annex 1 draft includes a new chapter on viable and non-viable environmental and process monitoring. The contamination control strategy and its dependence on trend analysis, process understanding, thorough investigation, and a commitment to progress is now an essential activity referenced multiple times through the document. There is also clear differentiation between qualification and monitoring, and quality risk management concepts are critical to successful implementation of system controls.

A global disinfectant standard for cleanrooms: Presenting a harmonised approach

Disinfectant efficacy testing is an essential part of a facility contamination control strategy. Pharmaceutical and healthcare products facilities must know that the products they are using can achieve effective levels of microbial kill across a range of surface types. The problem faced by microbiologists and production managers is that the various national and international standards use different methodologies. In addition, these standards and methods have not been written specifically for cleanrooms and the microbial test panels and logarithmic reduction expectations are not considered suitable. In order to develop an international standard suitable for all pharmaceutical facility cleanrooms, Ecolab has developed the Validex™ method, which is independently assessed in this paper. This method involves using 2 cm diameter disks, to target a 3 log reduction for vegetative bacteria in 5 minutes; and a 2 log reduction for fungi and bacterial spores in 10 minutes. The key criteria and rationale for selection, along with the methodology, are presented in this paper.

Some observations on protective efficacy of surgical clothing systems with additional clothing components concerning airborne bacteria-carrying particles measured during ongoing surgery

The main source of airborne bacteria-carrying particles is the staff and the patient. In order to reduce airborne bacteria-carrying particles from the staff, it is important that the surgical team wears a functional clothing system. This paper compares results from measurement studies of the protective efficacy, i.e., source strength, of a surgical clothing system with different additional clothing components. The studies were performed during ongoing surgery. The results show that the use of disposable hood or textile hood and the use of knee-length textile boots have considerable influence on the source strength, i.e., microbial air cleanliness in the operating room.

Agar Desiccation – The Causes and How to Address Them

Solid culture media, or agar plates, are prone to desiccation. The combination of warm, dry air and limited moisture content to achieve a solid finish leads to inevitable drying out and desiccation. Cracks in the media, a loss of volume or shrinkage away from the sides of the Petri dish are evidence of desiccation. Overall, this reduces the capability of the media to support the growth of organisms. The reduction in growth support capability is particularly so if the microorganisms deposited on the surface of the media are stressed. Why is Desiccation an Issue It is a well-known fact that microbes have three basic requirements for growth; a food source, warmth and moisture. Reducing the moisture content risks inactivating and or inhibiting growth. The purpose of monitoring for microbes through the use of solid media is to capture microorganisms from the manufacturing environment and create favourable conditions to support their optimum growth, thus allowing them to replicate and form visible colonies for inspection. Viable environmental monitoring is a challenging process to optimise for; you are looking for the chance of capturing one of the very few microorganisms present in your extensive manufacturing facility. To do so, you use solid culture media to take samples, snapshots in time, of your environment. Firstly, you have a vast space to monitor, and your monitoring activity needs to find the very few microorganisms present. If you have set your monitoring programme up suitably and you successfully capture organism present in the environment but then add desiccation you risk losing critical data. Desiccation leads to a reduction in these favourable conditions and potentially a loss of critical data and false-negative results. Desiccation of media is considered a significant quality issue as it can lead to the inhibition of growth and or cell death. The action of drying out of the media can lead to the formation of a skin on the surface. The skin formation inhibits the recovery of organisms, through «bounce» or «air bounce». As the purpose of environmental monitoring is to capture and support the growth of contaminants, this issue will result in inconclusive data gathering. Desiccation is an inevitability. Cleanroom environments are by their very nature, high airflow facilities which, as you will see below, is a primary reason for the loss of moisture from agar plates. It is, therefore, important to ensure media qualification studies include a review that post use, your media, can meet the 70% growth rate recovery as specified in USP <1227>.