1.What is Riboflavin coverage study?
2.if the residue not meeting the acceptance criteria what shall be done? How to proceed?
1.What is Riboflavin coverage study?
1.What is mock soiling, what should be the batch size in general?
2. What is general difference between ADE & PDE
1.What is periodic cleaning verification and when and why it should be done?
2. What is the criteria for cleaning and assessment for product non contact parts?
Which application are you using Riboflavin for?
The intention of conducting Riboflavin coverage study defined as Fluorescence test for examination of
cleanability in for low-germ or sterile process technologies. In brief it includes three subsidiary tests as follows;
- Weak point test
- Cleanability test
If the cleanability test for the component being examined is failed, you’re supposed to follow the deviation management instructions and conduct a root cause analysis to identify the cause of this failure.The test is then repeated after correction measures have been carried out (e.g. modification of
the cleaning procedure) and possibly coordination with the client. The new test conditions must be
When carrying out the weak point test it may occur that it is not the associated criterion of quality that is
met, but rather that of the cleanability test. In this case, it is recommended to mutually acknowledge the
weak point test as cleanability test.
How is the time frame for storage of uncleaned equipment is established and how it’s conducted and ideally how many batches should be considered?
What are the types of swab stick we use for cleaning validation, is it acceptable to use different brand as used in recovery study --during analytical method.
How you will certify and Define the acceptance criteria for removal of flavour and order from the equipment during CV?
Change in source of API shall trigger cleaning Revalidation?
All changes that may affect product quality or reproducibility of the process should be formally requested, documented and accepted. The likely impact of the change of facilities, systems and equipment on the product should be evaluated, including risk analysis. The need for, and the extent of, re-qualification and re-validation should be determined.
You need to take “Dirty Equipment Hold Time” study. The effectiveness of a cleaning procedure may depend on the properties of the dirty equipment as well as on the characteristics of residuals, whether they are fresh and still wet, or got dried after some time of holding. That means the hold time of dirty equipment should be chosen according to your needs. The hold time should be covered by your cleaning validation.
To avoid this effort, you can of course postulate that cleaning has to be done immediately (maybe within
few hours) after usage of the equipment.
As indicated in the EMA Health-based Exposure Limit document, page 10, footnote 4 way down at the bottom of the page in tiny type. The terms PDE and ADE are effectively synonymous.
In addition, as indicated in “Overview of comments received on 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities’ (EMA/CHMP/ CVMP/ SWP/169430/2012)” on page 22, Stakeholder 14, the following comment has been accepted "Equivalent approaches have been proposed or used by companies and professional societies (e.g. ISPE) using slightly differing terminology (e.g. ADE, Acceptable Daily Exposure instead of PDE). Existing hazard assessments should be acceptable to the EMA even if the exact terminology used therein does not correspond in every detail to the one proposed in the present guideline."
We have been authoring OEL/ADE monographs for many years, and these documents have been accepted by regulatory agencies. Even though the ADE and PDE formulas look slightly different, the outcome will be the same.