Worst case product determination (Should I use bracketing)

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Hi guys

I’m newbie in the area of cleaning validation and I desperately need your help. In our site we are manufacturing currently 6 products. Four of them are immunostimulators. I need your help to determine the worst case product for cleaning validation purpose. In my opinion the worst case product is product B because the API of the product is insoluble in water and the minimal effective dose is one of the lowest. Another thing I do not understand is the so-called bracketing procedure. Should I split the products into groups (i.e. insoluble in water, products with low therapeutic dose and so on), and then determine the worst case products in each group separately or in my case this is unnecessarily, due to the small number of the products?

+----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | Product | API | API per tabl| Tabl mass | Batch size | API solub | Min Dose | MDD | +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | A | Methamizole sodium | 0.500 g | 0.600 g | 80 000 tabl | Very soluble| 0.500 g | 3.000 g| +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | B | Cinnarizine | 0.025 g | 0.150 g | 333 333 tabl | Insoluble | 0.025 g | 0.225 g| +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | C1 | freeze-dried lysate and | 0.050 g | 0.200 g | 206 000 tabl | Soluble | 0.050 g | 0.050 g| | (for adults) | killed bacterial bodies | | | | | | | +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | C2 | feeze-dried lysate and | 0.025 g | 0.140 g | 300 000 tabl | Soluble | 0.025 g | 0.025 g| | (for children) | killed bacterial bodies | | | | | | | +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | D1 | freeze-dried lysate and | 0.050 g | 0.180 g | 200 000 tabl | Soluble | 0.050 g | 0.050 g| | (for adults) | killed bacterial bodies | | | | | | | +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+ | D2 | feeze-dried lysate and | 0.025 g | 0.120 g | 300 000 tabl | Soluble | 0.025 g | 0.025 g| | (for children) | killed bacterial bodies | | | | | | | +----------------+-------------------------+-------------+-----------+--------------+-------------+----------+--------+All products mentioned in the table above are manufactured on the same equipment.

Equipment train

+-------+ +------------+ +-------+ +------------+ +--------------+ +-----------------+ | Mixer | => | Granulator | => | Dryer | => | Granulator | => | Tablet press | => | Blister machine | +-------+ +------------+ +-------+ +------------+ +--------------+ +-----------------+

2

We are currently reviewing our cleaning validation procedure, as in the past we assessed for all API’s that required cleaning. We have almost 20 products that currently require cleaning and have grouped them based on insoluble / toxic or soluble / toxic, and are cleaning for the worst case in each group. Equipemt train, batch size, etc also need to be considered. a risk assessment for each group is also a good idea, as it considers the other API’s under the worst case that could potentially cause cross contamination. Grouping API’s can reduce your validation activities, which is good allround. From looking at the list you posted, you could potentially group your immunostimulators and clean for the worst case - D2 - based on strength and conc. of active.

Hope im going in the right direction

Regards