I have been given responsibility for developing a cleaning validation strategy for a dedicated[/u] facility producing a single ocular implant[/u][/b] and I need some advice as I am new to the field of cleaning validation.
The product we make is an ocular implant consisting of a 2.5mg tablet containing 0.59mg of steroid in a PVA based delivery module. Total implant weight is 9.5mg. The implant releases the steroid over a 36 month period with the target dose of 0.3ug/day.
In the assembly stage the implant is constructed using 120 assembly plates, each plate has a surface area = 8.8cm2, each of which hold 12 implants.
Total number of implants made = 120*12 = 1440
The plates are then washed using a detergent.
I need to determine the maximum allowable detergent residue on the plates & this is where I run into difficulties.
Detergent LD50 (Oral,Rat)= 2000mg/kg
Total surface area of plates, 120 x 8.8 = 1056cm2
NOEL=20000.0005 = 1.0mg/kg
Acceptable Daily Intake (ADI) = 1.0mg/kg70kg*(1/10,000) = 0.007mg
For the Maximum Allowable Carryover MAC = (ADIB)/R
where B smallest batch size & R denotes largest daily dose made in the equipment.
In my case, do I use B as equal to the total number of implants made multiplied by the weight of the active tablet, ie 14402.5mg = 3600mg
and can I put R as being equal to the target dose of 0.3ug/day (CASE 1) or would it be a case where it can be assumed that all the steroid is released in a single dose, ie 0.59mg (CASE 2)
CASE 1 result MAC = [(0.007mg3600mg)]/0.0003mg = 84,000mg
CASE 2 result MAC = [(0.007mg3600mg)]/0.59mg = 42.7mg
Or can I put B (smallest batch size) as being a single assembly plate producing 12 implants, 122.5mg = 30mg
giving: CASE 3 MAC = [(0.007mg30mg)/0.0003mg] = 700mg
or CASE 4 MAC = [(0.007mg*30mg)/0.59mg] = 0.36mg
The intended swab area is 25cm2, and the absorbing solution volume is 45cm3.
Thus giving an analytical surface limit (ASL)
[(MAC/total area)swabbing area]/Volume of desorption solvent
for the 4 cases of:
CASE 1 MAC = 84,000mg, total surface area of 1208.8cm2 = 1056cm2
ASL = (84,000mg/1056cm2)*25cm2 = 1989mg = 1989000ug/45cm3 =
44200ppm
CASE 2 MAC = 42.7mg, total surface area of 120*8.8cm2 = 1056cm2
ASL = (42.7mg/1056cm2)*25cm2 = 1.0mg = 1000ug/45cm3 = 22ppm
CASE 3 MAC = 700mg, total surface area of 8.8cm2 (single assembly plate)
ASL = (700mg/8.8cm2)*25cm2 = 1989mg = 1989000ug/45cm3 = 42000ppm
CASE 4 MAC = 0.36mg, total surface area = 8.8cm2
ASL = (0.36mg/8.8cm2)*25cm2 = 1.0mg = 1000ug/45cm3 = 22ppm
I apologise for the length of this post but this is really causing me sleepless nights. Any help would be gratefully received.