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=2000*0.0005 = 1.0mg/kg
Acceptable Daily Intake (ADI) = 1.0mg/kg*70kg*(1/10,000) = 0.007mg

For the Maximum Allowable Carryover MAC = (ADI*B)/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 1440*2.5mg = 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 = [(0.007mg

*3600mg)]/0.0003mg = 84,000mg*

CASE 2 result MAC = [(0.007mg3600mg)]/0.59mg = 42.7mg

CASE 2 result MAC = [(0.007mg

Or can I put B (smallest batch size) as being a single assembly plate producing 12 implants, 12

*2.5mg = 30mg*

giving: CASE 3 MAC = [(0.007mg30mg)/0.0003mg] = 700mg

giving: CASE 3 MAC = [(0.007mg

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 120*8.8cm2 = 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.