Sanitation programme

 

The requirement for a written sanitation programme is made in the pharmaceutical business regulation and the EU GMP Guideline. The necessary plant hygiene measures are stipulated in these. In addition to personnel sanitation programmes (including clothing requirements, zonal behaviour, general code of conduct, personal hygiene, etc.), the specific assignment of the individual rooms in the plant to the defined cleanliness grade is also stipulated therein.

11.D.1 Cleaning procedure for rooms

Written cleaning schedules are compiled on the basis of the defined sequences and processes. These contain precise specifications on the type and frequency of the cleaning measures to be carried out. Depending on the cleanliness grade, different degrees of disinfection measures must also be carried out. The respective cleaning process must be established, i.e. how, when, with what and by whom cleaning is carried out. The selection of the appropriate cleansing agent or disinfectant and their application can be difficult and causes long test phases. Using the experiences and know-how of the manufacturers of cleaning agents and disinfectants through direct collaboration can be useful in compiling such instructions. The specifications, however, are defined by the pharmaceutical plant. There should be no dependency on a specific vendor.

The person responsible for cleaning and disinfection, i.e. who does it, and the person who is responsible for checking that it has been carried out are both stipulated.

A production room can be cleaned in various ways. Machines and facilities are cleaned according to the existing cleaning procedures (based on the results of the cleaning validation) (see chapter 8 Cleaning Validation). To this end, it may be necessary to dismantle machines in order to achieve sufficient cleaning. If individual parts of the equipment are taken out of the room, it must be ensured that no production remains, which could cause cross-contamination in other rooms, have adhered to the individual parts. Therefore, preliminary cleaning, e.g. aspiration and/or covering of containers must be carried out. After the machine has been cleaned, the rest of the room is cleaned. In doing so, it must be ensured that the cleaned machine does not become contaminated again. It may have to be covered to protect it from splash water, for example. During cleaning validation, the product contact surfaces are usually investigated, i.e. not rooms. Cleaning procedures for room cleaning are usually non-specific, but are fixed in writing.

They are based on the visual clean criterion. The suitability of the procedure is checked during monitoring.

There are currently no definitive legal requirements for cleaning rooms. The Hygiene Guideline of the former German Democratic Republic contained legally specific requirements on the cleaning intervals which can still be used at least as a starting point (see figure 11.D-2).

Depending on the structural and facility-related circumstances, the current cleanliness grade must ultimately be complied with. The efficiency of the measures is checked during monitoring. A model should then be presented that contains the necessary elements.

Hygienic areas

The assignment of the individual rooms in the plant to the hygienic areas (cleanliness grades) (see figure 11.E-3 and figure 11.E-4) is described in this section. This grades establishes the requirements and limits for monitoring (chapter 11.E Environmental monitoring).

General room cleaning

This instruction lists the individual rooms of the plant. The responsibilities for cleaning and disinfection measures and for the required execution intervals are listed. Groups of cleansing agents and disinfectants are assigned with the corresponding aids for application. The necessary change of disinfectants is established (see figure 11.D-4).

Cleansing agents and disinfectants

This is where the different permissible cleansing agents and disinfectants are named. They are coded in groups and enable simple connection to general room cleaning. The coding means groups can be formed, e.g. by application or by physical-chemical characteristics (see figure 11.D-5). This enables a simple replacement of agents, e.g. in case of changes. These instructions should also specify the necessary concentration and acting times of the respective agents, in order to enable proper application.

When selecting the cleansing agent or disinfectant, it is worth including the criterion of the tolerability of the agent for the employee. In addition to separate systems, combined agents for cleaning and disinfecting are also available on the market. It is expected that the cleansing agents used will not cause any interaction with the surfaces, i.e. will not bond with later release, and will not cause any modification of the surface structures. Compatibility with the material is important. This must be taken into account above all if different materials are processed in one room (e.g. floor tiles, walls). For example, if aluminium surfaces are cleaned with acid cleaners (e.g. citric acid), the roughness is increased.

For production and filling rooms in aseptic or clean room areas, disinfection with formaldehyde can be carried out depending on the technical circumstances. With an acting time of 6 to 16 hours, overnight disinfection is practical. Various agents are available for disinfecting tables, floors, walls and drains (alcohols, aldehydes, quaternary ammonium compounds or phenols).

Cleaning process

This section lists the different aids. The code grouping is used for classification in the clean room procedure (see figure 11.D-6).

The method of execution is important for the cleaning and disinfection result. Therefore, the application, dispensing and, if necessary removal, of the cleansing agent or disinfectant solutions must be fixed in writing as well as the concentrations used. In doing so, the experiences of the employees and the results from the monitoring should be consolidated. Simply wiping the floor with a mop is sometimes not sufficient. This simply redistributes the dirt, and mixes it with disinfectant. As an alternative, the floor can be flooded with subsequent aspiration. Automatic floor cleaning machines are another alternative for large area applications (e.g. corridors). In order to prevent transporting dust across the entire working area, it must be ensured that the aspirated dust is not blown out again. Cleaning is carried out in steps: application of the cleansing solution, floor wiping, and aspiration of the dirt solution; rinsing may also be included. Depending on the location, it should ideally be possible to qualify such machines and thus enable reproducible cleaning. The procedure must be matched to the individual circumstances.

11.D.2 Documentation

Room cleaning or disinfection is documented in the form of records. These are effectively room log books, which enable the traceability of products or batches. In addition to confirmation that the work has been carried out, they also give a status report on the room, which shows its cleaning status.

The type of production (product name, batch name for traceability) and the executed cleaning or disinfection are documented (see figure 11.D-7). Records that are hung up can be viewed easily, i.e. if they are hung up directly on site (outside a room, as a record inside the room could potentially become contaminated or could act as a contaminant), so that the cleaning status of a room can be seen directly from outside. The length of time for which this status can be retained must be defined, above all from a microbiological perspective. This means that, as with production devices for the production rooms, an expiration date for the cleanliness status must be defined.

The records should be checked in regular intervals by the head of department and compared with the current status. During monitoring, they should be critically reviewed in terms of their quality. The retention time for this data, as pharmaceutical secondary documentation, is the expiration time of the products produced in the rooms plus one year (at least 5 years)

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