31.03.23

Hygiene monitoring: The agony of making the right choice!

Hygiene monitoring refers to the systematic monitoring of measures aimed at preserving health. This practice is applied in various industries such as pharmaceuticals, biotechnology, cosmetics, and food production. Additionally, it is employed in settings like hospitals, pharmacies, commercial kitchens, and other areas with high hygienic requirements to oversee the hygiene of employees, products, and processes.

Summary

Hygiene monitoring is the simplified term for the general monitoring of measures taken to maintain health. This is especially true with regard to various microbiological contaminations, which can lead to direct and indirect infectious diseases, chronic diseases of various kinds, allergic reactions as well as epidemics.

Microbiological hygiene controls of various clean rooms, such as in pharmaceutical production, in operating theaters and quarantine rooms, in food production, in public areas and other hygienically sensitive areas, serve to prove the quality of one’s own hygiene management with tangible data through regular monitoring and to correct it if necessary.

Ultimately, hygiene monitoring confirms the quality assurance of products and services of all kinds as well as the efforts to ensure the safety of employees, patients, visitors and consumers, and last but not least, the immediate surroundings and the general environment.

Hygiene monitoring

Based on the EU standard EN 17141, “Cleanrooms and associated cleanroom areas – Biocontamination control”, – formerly EN ISO 14698-1:2003 and EN ISO 14698-2:2003 – a mix of sedimentation plates, sampling by swabs/swabs, active airborne bacteria measurements and surface investigations by means of swab plates is used for microbiological hygiene monitoring of production facilities in the regulated area.

The regulations require regular monitoring at a frequency high enough to detect deviations at an early stage and to ensure statistical significance of the data collection. The frequency of monitoring depends on factors such as the GMP class of the cleanroom, the risk assessment of the production process, the cleanroom design, interactions with people in the immediate environment, and existing historical data, which should be evaluated by trained subject matter experts.

Each cleanroom operator has the responsibility to define, justify and regularly adjust its monitoring frequency. Hygiene monitoring is used in pharmaceutical, biotech, cosmetics and food industries as well as in hospitals, pharmacies, commercial kitchens and other hygienically demanding areas to monitor employee, product and process hygiene.

The suitable measuring method: The agony of the right choice!

Various measurement methods are available for obtaining the required measurement data. Depending on the type of germs or infectious particles to be measured, the sampling volume, frequency, observation period and the appropriate method should be selected and carried out by specialists and their data carefully evaluated and communicated. In addition to classical culture-based microbiological measurement methods or direct and indirect detection methods of direct and indirect hygiene parameters, rapid microbiological methods and as well as alternative real-time microbiological detection methods are also available.

In the specialized laboratory or “on site” at the customer’s premises

In addition to highly specialized laboratories for microbiological sample or parameter analysis and the very specific evaluation of samples obtained during controls, “on-site” microbiological analysis methods provide further technologies for significantly faster and more targeted correction of existing hygiene measures.

While highly specialized central laboratories can deliver very good results in terms of quality and quantity with high accuracy, low detection limit and excellent specificity down to the DNA/genome and protein sequence level, the simpler methods of on-site measurements are usually less accurate and specific. On the other hand, the results are available much faster and corrective actions can be taken much faster. This is crucial in all areas where it is not possible to wait several hours or days for a result.

A combination and expertise of specific laboratory evaluations and of faster – often less precise – on-site measurement methods ensures a high quality of the entire service chain – from effective, fast and correct data collection and evaluation, a specialized analysis of the samples, through expert conclusions to the suggestion of hygiene control measures to be taken.

In general, for microbiological control, a self-optimizing system is proposed on a continuous basis, which identifies, performs, controls or monitors and adapts. This is a classical cyclic process of continuous improvement, in which the principles: Plan – Do – Check – Act (PDCA, i.e. Plan, Do, Control and Act), apply.

When creating and planning a suitable hygiene solution of an operational system for microbiological control, an adapted bioanalytics is the central cornerstone. This involves identifying all potential sources and pathways of microbiological contamination and planning and testing appropriate solutions on site or in the laboratory. During the implementation and application as well as the other phases of continuous improvement, especially the fast on-site measurement methods can help to monitor, check and maintain a chosen concept of measures or to correct it accordingly and thus to improve it.

In summary, the advantage or benefit of an adapted biocontamination control consists of a combination of different factors:

• Choice of appropriate on-site analyses and/or central laboratory confirmations through adapted and optimized microbiological measurement methods; this as a combination of “fast on-site” and “accurate and specific” in the laboratory
• Data analysis and risk assessment as well as preparation of a specific and system-optimized monitoring plan
• Competent recommendation in case of deviations as well as taking the appropriate corrective measures.
• However, short response times for carrying out the necessary analyses as well as the corrective, decontamination and hygiene work before major damage is caused to people, products or the environment are crucial.

Specific implementation in the various industries and the healthcare sector

A variety of different instructions are available, particularly for the pharmaceutical, biopharmaceutical, medical device and other life science industries, such as healthcare and hospitals, and related applications. All sectors and industries have in common that they own and/or use highly relevant and controlled areas for hygienic cleanliness or cleanliness.

In the regulated pharmaceutical and biopharmaceutical manufacturing industry, there are already numerous applicable standards and regulatory guidelines. These include the EU Annex 1 GMP Guide for sterile drug manufacturing and the FDA Guide for aseptic manufacturing. The pharmaceutical regulations of Europe and the USA also contain some guidance on certain related topics. Numerous other documents and technical articles are available from industry associations including the Parenteral Drugs Association (PDA), the International Society of Pharmaceutical Engineering (ISPE), and the Pharmaceutical Healthcare Sciences Society (PHSS).

In the healthcare and hospital sectors, EU guidelines including tissue and blood guidelines are available for specialty areas and similar areas controlled for cleanliness. National standards and guidelines are available for specialized operating rooms, isolation wards, and immunocompromised patient wards as part of infection control. In addition, aseptic drug mixing areas in hospital pharmacies, radiopharmacy pharmacies, and specialty laboratories such as stem cell laboratories commonly use guidance documents from the life sciences industry.

While regulations and standards are available for risk management of medical devices, such as EN ISO 14971, less guidance is usually available for microbiological control of other areas controlled for general cleanliness.

Even though regulations and standards are available in the food and related consumer goods industries, for example on food, beverages and cosmetics, insufficient guidance is available on microbiological control in areas controlled for cleanliness.

Sources

• DIN EN 17141:2020: Reinräume und zugehörige Reinraumbereiche – Biokontaminationskontrolle
• DIN EN ISO 14698-1:2003: Reinräume und zugehörige Reinraumbereiche – Biokontaminationskontrolle – Teil 1: Allgemeine Grundlagen
• DIN EN ISO 14698-2:2003: Reinräume und zugehörige Reinraumbereiche – Biokontaminationskontrolle – Teil 2: Auswertung und Interpretation von Biokontaminationsdaten
• EN ISO 14644-1:2015: Reinräume und zugehörige Reinraumbereiche – Teil 1: Klassifizierung der Luftreinheit anhand der Partikelkonzentration
• EN ISO 14644-2:2015: Reinräume und zugehörige Reinraumbereiche – Teil 2: Überwachung zum Nachweis der Reinraumleistung bezüglich Luftreinheit anhand der Partikelkonzentration
• EN ISO 14644-3:2005: Reinräume und zugehörige Reinraumbereiche – Teil 3: Prüfverfahren
• EN ISO 14644-4:2001: Reinräume und zugehörige Reinraumbereiche – Teil 4: Planung, Ausführung und Erst-Inbetriebnahme
• EN ISO 14644-5:2004: Reinräume und zugehörige Reinraumbereiche – Teil 5: Betrieb
• EN ISO 14644-7:2004: Reinräume und zugehörige Reinraumbereiche – Teil 7: SD-Module (Reinlufthauben, Handschuhboxen, Isolatoren und Minienvironments)
• Enzler h-tec Einstleistungen – Angewandte Hygienetechnologien
• ISO 14971, Medical devices – Application of risk management to medical devices
• Point H.A.C.C. (HACCP) system and guidelines for its application. 1995 Codex Alimentarius Commission. Alinorm 97/13. Annex to Appendix II. Joint FAO/WHO Food Standards Programme. Food and Agricultural Organization of the United Nations, Rom, 1995.
• European Commission EudraLex „The Rules Governing Medicinal Products in the European Union“, Volume 4.
• EU Guidelines for Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Annex 1 – Manufacture of Sterile Medicinal Products, 25. Nov. 2008
• FDA Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice. September 2004.
• IS0 18593:2018: Mikrobiologie der Lebensmittelkette – Horizontales Verfahren für Probenahmetechniken von Oberflächen