Cleaning Validation

Cleaning Validation

Certain to be clean

The manufacturing of pharmaceutical active ingredients and medicines takes place in a strongly regulated environment. For reasons of patient safety, impurities and cross-contaminations as part of the production process must be able to be ruled out. The authorities place great value on effective and validated cleaning processes for the removal of unwanted materials and coverings from surfaces and production items.

The legal regulations can be found for example in the PIC/S-Guidelines, the EG-GMP guidelines on Good Manufacturing Practice or in the Guide to Validation of Cleaning Processes from the FDA.

Are you looking for an analysis partner for cleaning validation? Do you require advice in the interpretation of legal requirements or do you need support in planning the analysis of your cleaning validation?

As a GMP-accredited and FDA-certified test laboratory in Switzerland with many years of experience, we can provide you with support in method development, validation and routine testing of the analyses as part of your cleaning validation. We will test for you in accordance with legal guidelines or to your own specifications.

 

Take advantage of our experience. We will be happy to advise you.

Read on here for more information or contact us.


The goals of the cleaning process

Cleaning of the production facilities (here using spray drying) must be validated
Cleaning of the production facilities (here using spray drying) must be validated

There are a number of objectives to be considered, depending on the way that the facilities are used. If only one active ingredient is manufactured in a production facility, then it needs to be ensured that there are no carry-over effects after cleaning has been performed. Substance carryover of the same substance to the subsequent batch must be prevented. Additionally, prevention of contamination from degradation products can be a target criterion.

In multi-product facilities, the focal point in the active ingredients area is mainly on the prevention of cross-contamination: substance carryover of an active ingredient into the production of the next active ingredient.

Before the start of a cleaning validation, suitable acceptance criteria that are necessary for successful cleaning must be defined.

What do we understand by dirt / impurities?

This includes all types of microbial impurities, active ingredients, excipients, particulate impurities and also cleaning agents. Selection of the most suitable cleaning process depends on the type of contamination. Selection of the most suitable analytical method is dependent upon the type of impurities and the cleaning agents used.

Typically, acceptance criteria will be defined in the validation protocol for these impurities.

Sampling procedures

Example of a SWAB being performed on a glass slide
Example of a SWAB being performed on a glass slide

Probably the most commonly used techniques are the SWAB procedure or the rinse method.

In the SWAB procedure, sampling is performed directly from the surface using a swab. To do this, precise instructions must be created to ensure that high-quality and reproducible results are achieved.

The rinse method, in which sampling takes place while rinsing is being carried out, is particularly suitable for hard to reach surfaces e.g. in pipework systems or in narrow or angled devices.

Both methods have their advantages and disadvantages. The selection of a suitable method depends upon the type of problem.

In general, steam condensate, follow-on batches or placebo batches can also be investigated.

The challenge for the analysis - which method is the most suitable?

The type of analysis can be considerably different and must be adjusted for the lead substance. It is important to achieve the required limit of detection (LOD) and limit of quantification (LOQ) with the method selected.

In most cases, it is recommended to carry out microbiological tests (for example in the form of a bioburden). These tests are usually required to determine the downtime between cleaning intervals and production runs.

Examples of instrumental analysis methods (a selection):

Optical methodsSeparation processElectro-analytical
process
Other methods
IR / NRHPLC, GC, DCpH, potentiometry,
conductivity,
amperometry
TOC, ELISA
UV / VISElectrophoresisSurface tension

Selection of the method of analysis is dependent on the type of problem. The effort made should be appropriate for the type of problem. The decision can be made to choose an appropriate selective method or non-specific method.

Validation of analytical methods

To conform with GMP cleaning validation, the analytical methods must be validated in accordance with the requirements of the ICH guidelines. Please read the section Method Development and Method Validation, to see which aspects need to be taken into consideration.

What are the arguments for outsourcing the analysis of the cleaning validations?

  • Access to the greatest level of specialist knowledge and a variety of analysis methods
  • Being free from routine work and the opportunity to focus on core tasks
  • Capacity peaks can be overcome

Our services in detail:

HPLC analysis: Determination of impurities
HPLC analysis: Determination of impurities

contact person

sales pharmaceuticals

Michael Trösch Graduate Chemist HTL

Tel. +41 58 434 42 00 Fax +41 58 434 42 01 service@ufag-laboratorien.ch

link

directory of services

Pharmaceuticals - analysis

ordering information

Help for your order

newsletter

Subscribe now!

Subscribe now to the UFAG LABORATORIEN newsletter!

Title*
*Mandatory fields

infrastructure and methods

Instrumental resources