Increasing hygiene requirements and the exciting journey to develop a hygiene concept within the framework of GMP Annex 1

Bettina Ernst

The hygiene requirements for the industrial production of pharmaceuticals, food, and cosmetic products are continuously increasing. Globalization and the widespread distribution of products for humans and animals can have worldwide impacts in case of emergencies. Although all three sectors have different regulations, their hygiene standards are similar, sometimes even identical. Companies must establish hygiene standards and continuously monitor their compliance, set up suitable production sites, and ensure clear labeling and traceability of the goods.

The regulations in pharmaceutical manufacturing are generally stricter than in the food sector. This is not only about hygiene in production. Product quality, filling processes, and marketing are of great importance here, as contamination or incorrect dosages in production can quickly lead to far-reaching and serious consequences.

To prevent errors or to eliminate them as much as possible, the pharmaceutical industry imposes high requirements on the GMP quality assurance system, which all manufacturing companies must adhere to. The legal regulations, directives, and guidelines are issued by governments and international organizations. The aim is to bring safe and effective medicines to market. The regulations from GMP are not only important for pharmaceutical companies but also for machine builders and their suppliers, making the development of a good hygiene concept within GMP Annex 1 indispensable.

The planning, management, and implementation of these hygiene requirements involve what we might call a "larger journey." First, hygiene concepts are developed, which should then be tested for compliance with a QMS audit. This should be followed by a QMS revision, and subsequently, the CAPA management further scrutinizes the product quality in detail.

With the development of the hygiene concept or plan, the engine is started, and the journey into GMP Annex 1, DIN EN ISO 14644-5 operation, VDI 2083 Sheet 15 Personnel at the clean workplace, VDI 2083 Sheet 5.1 operation of cleanrooms, and Good Distribution Practice for human medicinal products begins with goal setting. Is the destination of the journey set?

What makes the journey almost perfect? Good preparation is key before starting a trip. This includes environmental monitoring. It monitors the environment, equipment, cleanroom technology, and the effectiveness of disinfection measures. Monitoring can be process-related or batch-related. Passive and active methods are available for microbiological testing of the room air. Surface testing can be done via contact, swab, and rinse methods. For sterilization or decontamination with aerosols or by nebulizing sterilization test isolators, as well as sluices and cleanrooms, various chemicals can be used.

The effective assessment of monitoring looks as follows:

– Risk assessment based on knowledge
– Process data
– End product
– Facility
– Equipment
– Criticality of specific processes
– Microbiological flora

The effective assessment of monitoring:

– Risk assessment based on knowledge
– Process data
– End product
– Facility
– Equipment
– Criticality of specific processes
– Microbiological flora

Monitoring is carried out during critical processes, considering the highest contamination risk. This provides justification for the selection, alignment, and positioning of monitoring points.

Of course, material and personnel flow play a major role. The following points are considered:

– Separation of material/personnel lock
– No hand washbasins in the B-change room area
– Approved list for class A/B with materials/equipment to be introduced
– Unapproved items must be pre-approved
– Entrance and exit doors should not be open simultaneously
– Visual or acoustic signals for RRK C/D
– Determine maximum personnel number

The next step is to prepare the clothing concept. Like any journey, preparation must include considerations about clothing. In the pharmaceutical industry, the changing process is evaluated and qualified. This also includes donning the clothing. The requirements for the cleanliness of production environments are also increasing. Proper behavior in the cleanroom depends on many factors. Proper donning of cleanroom garments is often underestimated. It may happen that improper behavior occurs frequently because it is seen as obvious. A re-evaluation of compliance with the changing process should be carried out annually. The cleanroom orderliness of the respective user is central here and, of course, specific to the cleanroom class. Let’s consider RRK A/B: clothing – fingers, forearms, chest, hood (face mask/forehead).

Summary of the clothing concept:

– Clothing specific to cleanroom classes
– Changing procedures
– Storage of clothing: lockers should not contribute to contamination
– Appropriate sizes
– Hygiene

The customer is still preparing for the long journey into GMP requirements Annex 1 and now reviews the requirements of pest control.

– Design and setup of operating rooms to prevent
– Insects
– Rodents
– Other animals
from entering.
– Preventive pest control program

Now, the suitcase for the journey is being packed; what is included:

– GMP Annex 1
– DIN EN ISO 14644-5 operation
– VDI 2083 Sheet 5.1 operation of cleanrooms
– Good Distribution Practice for human medicinal products
– VDI 2083 Sheet 15 personnel at the clean workplace

Is the suitcase fully packed? Not quite, because a few tools are still needed for the journey:

– Gap analysis
– Risk analysis
– KPIs

With this perfect preparation, the wonderful journey can begin. Here is a brief explanation of the tools packed in the suitcase.

The gap analysis tool consists of:

– On-site inventory
– Document review
– Risk identification
– And a recommended course of action