Cleaning validation

A cleaning validation serves to prove that defined cleaning and disinfection measures of production sites and associated equipment are suitable and sufficient regarding the production of harmless products. The use of the term “cleaning validation” includes not only the inspection of the cleaning measures but also the inspection of the disinfection. The aim is to ensure that no microbiological and/or chemical residues are left in the products. The products must meet the set requirements.

In the ISO 22716 (Cosmetics GMP)¹, it is required in the chapter on company sites that cleaning and, if necessary, disinfection must be carried out to protect the individual products. Furthermore, the agents used (cleaning agents and disinfectants) must be specified for this purpose, they must be effective and must be adapted to the respective needs of the individual areas. Analogously, this procedure is also required for the equipment.

Due to the mentioned requirement for the effectiveness of the measures, a subsequent check must be carried out to ensure this. ISO 22716 is also to be regarded as directly applicable law via the direct reference to EU Cosmetics Regulation 1223/20092. Furthermore, the IFS HPC Standard (Version 2)3 requires in Part 2 (List of audit requirements) under the section cleaning and disinfection:
This standard thus explicitly requires the performance of a risk analysis and assessment as well as a subsequent validation of the cleaning and disinfection measures carried out (cleaning validation). The difference between cleaning (removal of visible and non-visible contamination) and disinfection (reduction of microorganisms) should be pointed out.

Cleaning validation step by step

Step 1: Cleaning and disinfection plans must be available as part of a written hygiene programme in companies operating in accordance with cosmetic GMP. These plans form the basis for carrying out a cleaning validation. Cleaning and disinfection plans must be defined for the individual areas within the framework of an overall written hygiene programme in the production sites. These serve to protect the individual products as well as to avoid a possible risk to the consumer. When defining these plans, the following points must be considered: 

• clear definition of agents used (exact description, concentration, exposure times, instructions for use, etc.),
• use of effective agents (depending on product type, residue, etc.)
• clear definition of the areas or equipment to be cleaned and/or disinfected,
• detailed description of procedures,sequences and processes (e.g.how a piece of equipment is disassembled,cleaned and reassembled),
• frequency of cleaning and, if necessary, disinfection,
• documentation requirements,
• clear responsibilities and use of trained personnel, and
• adaptation in case of changes (new products, conversions, etc.).

With regard to the selection of suitable cleaning agents and disinfectants, please refer to the literature.

The manufacturers of the respective products can also provide valuable information and tips.

Step 2: Creation of validation plans bases on the previously defined cleaning and disinfection plans (step 1) and a hazard analysis and assessment of associated risks, a so-called validation plan is created for the corresponding areas. This validation plan essentially includes:

• determination of relevant areas and facilities for each process step,
• selection of representative areas and facilities as well as representative cleaning and disinfection steps,
• description of the facility, the work equipment, or the premises,
• description of cleaning and disinfectionwith details of the individualsteps, agent used, duration and time of action,
• sampling point or sampling area,
• type of sampling,
• specification of test parameters and analytical procedures, and
• determination of limit values or acceptance criteria.

The focus here is on areas and premises where direct contact with the product is possible (e.g. preparation, bulk production, filling, etc.). Other areas such as raw material storage are also considered (with less relevance).

Step 3: Carrying out the cleaning validation following possible residues are considered within the scope of the cleaning validation:

• product residues (mostly from predecessor product, predecessor formulation),
• residues of cleaning agents or disinfectants,microbiological contamination (bacteria, yeasts, and moulds)

The testing of the above-mentioned residues and contaminations must be carried out using suitable methods (validated or accredited procedures). Furthermore, the respective method must be sensitive enough to detect residues in small quantities (usually at least 10 mg/kg for chemical residues or microorganisms not  detectable in 1g of product) safely and reliably.

It should also be noted that it must be possible to take samples at a defined sampling point (access possible, sampling tap, etc.). Table 1 provides an overview of the most common test parameters and the corresponding requirements. The sampling locations and the test parameters are determined specifically for each cosmetic company, depending on the type of plant and equipment and the respective products. In addition to this table, further product-related test parameters can and should be added, which are known to possibly cause problems (worst-case consideration).

These tests are used to check the efficiency of the cleaning and disinfection carried out and to answer the question of the extent to which residues from a pre-product are still transferred to a subsequently filled product (follow-up product), e.g. preservatives.

Furthermore, testing for the absence of residues from cleaning agents and disinfectants (active substances) shows that the cleaning process including times, temperatures, etc. works. The inspection of microbiological cleanliness also serves as evidence of sufficient cleaning and disinfection.

If deviations occur during a cleaning validation or the specifications and limit values are not complied with, appropriate measures and adjustments to the processes are necessary (e.g. extend rinsing times etc.) until the corresponding specifications can be complied with. The analytical tests as such can be carried out both in-house and with the support of external, accredited laboratories. Sometimes high analytical equipment is needed, which makes it necessary to involve external laboratories or which might be also required by the trade.

Step 4: In the validation report, the performance of the cleaning validation is documented in detail. This report builds on step 2 (validation plan) and complements it. Any anomalies are documented (can also be implemented in the same document as from step 2) and a decision is made on the basis of the acceptance criteria whether, and if so, further measures or an adjustment of procedures etc. are necessary or whether the cleaning validation carried out is successful. The process is revalidated after specified time intervals (see step 5).

Step 5: After successful initial validation, regular revalidation is required. The frequency of such revalidations must be determined internally (e.g. every 2-3 years without changing procedures etc.). Irrespective of this, a cleaning validation must be carried out again (including associated adjustments to the cleaning and disinfection plans as well as validation plans) with 

• changes to premises and/or new facilities,
• change of prcedures,
• changed cleaning and disinfection steps or
• new product recipes.

The decisive factor here is that the changes listed above have a direct or indirect influence on the product quality. The extent to which minor changes (e.g. adaptation of a formulation while the basic formulation continues to exist) make a renewed cleaning validation necessary or not must be checked on a case-by-case basis with the appropriate know-how. If necessary, a new hazard analysis and risk assessment must be carried out.

Summary

The legislator and cosmetics law require sufficient operational hygiene in cosmetics businesses, combined with a corresponding check of the cleaning and disinfection carried out (cleaning validation). It is therefore not sufficient to simply carry out the corresponding cleaning and disinfection steps in the businesses; rather, the effectiveness of the same must be demonstrated.

Here, a precise consideration and evaluation of the individual steps and their performance is necessary, and appropriate expert knowledge is indispensable. 

References

1 ISO 22716 (2008-12) Cosmetics – Good Manufacturing Practices (GMP) – Guidelines on Good Manufacturing Practices
2 Regulation (EC) No. 1223/2009 on cosmetic products, current version
3 IFS HPC Version 2 – Standard for the assessment of products/processes of suppliers manufacturing household and personal products
4 ISO 17516 (2015-02) Cosmetics – Microbiology – Microbiological limits