A3P

Log in

Recovery rate determination is a preliminary and necessary step during cleaning validation. (La Vague 54)

The determination of recovery rate enables the validation of sampling techniques by precise measurement of the amount of contaminant that can be retrieved.
This study demonstrates that residues present on the surface of equipment can be adequately quantified by a combination of the analytical method and the sampling methodology. These studies provide a scientific basis which then allows the use of sampling and analytical methods during a cleaning validation exercise.

1Recovery rate studies of chemical residues are generally conducted in laboratories on different coupons (glass, stainless steel, plastic…) depending on the validation requirements. They consist in depositing a defined quantity of chemical residue and in applying the sampling method selected.
Recovery rate determination is a regulatory requirement (1).

 

Two sampling methods are mainly used in cleaning validation.
Sampling by swabbing, the recommended technique which targets the equipment surfaces that are most difficult to clean, and rinse water sampling which gives an overall view of the residual contamination of an item of equipment.
The sample will then be analyzed in accordance with the analytical method identified.
During the recovery study, it is really a question of simulating the sampling conditions achieved during a cleaning validation exercise (same solvent, same type of swab, same methodology, etc.)
It should be noted that for a rinse water sample, it is often difficult to replicate the laboratory rinsing procedure. Here “worst case” conditions should be utilized, while trying to reproduce the rinsing conditions as closely as possible.
A method for simulating “worst case” conditions may for example consist in placing the coupon at the bottom of a beaker and applying gentle agitation for a period similar to the rinsing time.

2

Photo 1. Study of recovery rate by swabbing a stainless-steel coupon

3

Photo 2. Study of the recovery rate by rinsing on a stainless steel coupon

The recovery rate is a combination of several performance elements: the recovery efficiency (relationship between the quantity retrieved and the quantity deposited), the analytical efficiency (relationship between the quantity retrieved and the quantity measured) and in the case of swabbing the desorption efficiency of the swab.

A recovery rate must be established for all the surfaces sampled. For this a study may be conducted on each type of surface to be sampled. An alternative to this is to demonstrate equivalence in terms of percentage recovery between several types of surface. The study can then be conducted on a single surface from the group of surfaces judged equivalent.

Another approach consists in excluding from the study surfaces sampled representing less than a percentage (such as 1% or 2 %) of the total surface area of the equipment (example of an equipment item composed of 98 % stainless steel and 2 % PTFE). In this particular case, the recovery rate used will be the lowest recovery rate of all the other types of surface studied (2).

In 2010, Destin A. Leblanc, President of Cleaning Validation Technologies, explained that the recovery rate should decrease proportionately when the quantity of residue increased.
To illustrate this, he took the example of a snow shovel:
“If I have permission to pick up as much snow as possible from a pavement with a single pass of a spade, it is likely that with only 7 centimeters of snow, my sample (a spade) will retrieve a relatively large quantity of snow.
This value could be between 60 to 80% of the snow present on the area sampled.
On the other hand, if I were to use the same spade and the same sampling procedure on a pavement covered with 70 cm of snow, I could only collect 30 to 40 % of the snow present on the area sampled”. Saturation of the swab is one of the reasons that could explain this phenomenon (3).

However, Destin A. Leblanc specifies that some studies have demonstrated a linear recovery rate for different quantities of residue deposited. Ultimately, the assumption is that the reduction in recovery rate would be only observable in a study conducted over a wide range.
If recovery rate studies were performed at significantly different levels (by factors of at least 10 or 20), then the percentage of recovery could diminish. However, there is little value in recovery rate studies involving multiple levels of contaminant. For this reason, it seems preferable to perform a recovery rate study on a single quantity of deposited residue, preferably close to the acceptance limit.
Performing several tests for the same quantity of deposited residue seems more judicious as they will give a better idea of the variability of the sampling process (4).

For sampling by swabbing it seems preferable to take account of inter-operator variability and to perform the study with two people. Rinse sampling is not significantly operator-dependent, hence the study can be conducted with one person.

The FDA specifies that industry must challenge its analytical methods in order to obtain an acceptable recovery rate. A recovery rate below 50% generally calls the sampling method into question.


Two options are generally offered to manufacturers:

- The first option consists in using the recovery percentage to correct the analytical result measured. For example, if the recovery rate is 78%, then the analytical value obtained will be corrected by dividing it by 0,78.
- The second option consists in requiring that the recovery percentage is in a particular range so that no correction is required. For example, if the percentage is between 75% and 100% no correction factor will be necessary.(5)

It should be noted that recovery studies may not be necessary for some residues which are known to be easily soluble in water, such as sodium hydroxide and phosphoric acid used as cleaning agents.

Should a recovery rate also be determined to quantify the bioburden? Because of the variability inherent to counting bacteria, it does not seem judicious to determine a recovery rate in the same way as for a chemical residue. Within the meaning of USP 1227, the microbial recovery rate consists in performing a study on the absence of inhibition of bacterial growth by the sampling method.(XNIMX)


Bibliography

(1) BPF (GMP), Part II, Chapter 12.74
(2) Technical report n°49 - Points to Consider for Biotechnology Cleaning Validation
(3) Destin A. Leblanc, Cleaning Validation Technologies, Cleaning Memos October 2010
(4) Destin A. Leblanc, Cleaning Validation Technologies, Cleaning Memos September 2013
(5) Destin A. Leblanc, Cleaning Validation Technologies, Cleaning Memos December 2012
(6) USP 1227 “Validation of Microbial Recovery ” from Pharmacopoeial Articles FDA - GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES

By Sophie BOURGOIS - ASPEN Notre Dame De Bondeville

 


pdf
 
PDF version