Equipment Name: FBD Determination of Acceptance Criteria for Cleaning

Add Company Name/Logo Here

Location: Tabletting Block Validation Studies
Compiled By: Ovais ORAL PRODUCTS Date 2/7/2007
INSTRUCTIONS:
INSTRUCTIONS:

Sampling Method Swab Sampling Fill in

Fill in the
the Coral
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inp
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Parameter Description Value Units

Product A Product selected for cleaning validation study (worst case) Product No. 5
AI Active ingredient in Product A Mefenamic Acid
Product B1 Product with largest MDD value Product No. 1
Product B2 Product with smallest batch size Ciprofloxacin HcL Tablet
CA Active principle present in the cleaning agent AlkylBenzene Sulphonate
I Smallest strength of Product A manufactured 500.000 mg/day
J Maximum number of dosage units of product B taken/day 16.000 Units/day
K Number of dosage units per batch of final mixture of Product B1 240000.000 Units
LD50-AI Lethal Dose 50 for active ingredient in Product A 740.000 mg/kg
LD50-Detergent Lethal Dose 50 for the detergent 240.000 mg/kg
W Average human body weight 70.000 kg
L Equipment surface area in common between Product A & B1 5000.000 cm²
N Batch size of Product B2 15.000 kg
U Swab area 25.000 cm²/Swab
SF Safety Factor * 0.001
* Give justification for using safety factor other than 0.001 in the Protocol

Summary: MACO for both AI & CA to subsequently manufactured product

MACO
Criterion
Active Ingredient Cleaning Agent INSTRUCTIONS:
INSTRUCTIONS:
Dose 37.500 mg/25 cm² Fill in
Fill in the
the Visual
Visual Clean
Clean Limit
Limit for
for both
both AI
A
Toxicological 1.943 mg/25 cm² 0.630 mg/25 cm² Agent (Read
Agent (Read the
the comment
comment for
for more
more info)
info)
10 ppm 0.750 mg/25 cm² 0.750 mg/25 cm²
Visual Limit 1.000 mg/25 cm² 1.200 mg/25 cm²

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author (mohammad@xepasp.com for any changes
author (mohammad@xepasp.com for any changes required to required to be
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 This spreadsheet
This spreadsheet may
may not
not be
be resold
resold or
or distributed.
distributed. Please
Please request
request
author (mohammad@xepasp.com for any changes
author (mohammad@xepasp.com for any changes required to required to be
be
made).
made).
Copyright @ Mohammad Ovais, Pharmaceutical Scientist.
Formulas used for calculation:

A) Dose criterion (0.001)

mg of active ingredient in product A permitted per 25 sq cm swab area = (I/J) X (K/L) X U

Where
I = (SF * Smallest strength of product A manufactured)/day expressed as mg/day & based on the number of mg of active ingredient
J = Maximum number of dosage units of product B taken/day
K = Number of dosage units per batch of final mixture of product B
L = Equipment surface area in common between product A & B expressed as cm²
U = Swab area (25 cm²/swab)

B) Toxicological Criterion

mg of active ingredient in product A permitted per 25 sq cm swab area = NOEL x K x U

SF x J x L
Where
NOEL = No observed Effect Level = NOEL = LD50 X (W/E)
LD50 = Lethal Dose 50 in mg/kg animal for active ingredient in product A

E = Empirical Constant = 2000

S = Safety Factor = 0.01 - 0.001 (for Oral Products)
J = Maximum number of dosage units of product B taken/day
K = Number of dosage units per batch of final mixture of product B
L = Equipment surface area in common between product A & B expressed as cm²
U = Swab area (25 cm²/swab)

C) 10 ppm Criterion

mg of active ingredient in product A permitted per 25 sq cm swab area = R X (N/L) X U

Where
R = 10 mg active ingredient in product A/kg product B
N = Number of kgs per batch of final mixture of product B2
L = Equipment surface area in common between product A & B expressed as cm²
U = Swab area (25 cm²/swab)
Equipment Name: FBD Determination of Acceptance Criteria for Cleaning
Add Company Name/Logo Here
Location: Tabletting Block Validation Studies
Compiled By: Ovais ORAL PRODUCTS Date 2/7/2007

Sampling Method Rinse Sampling

Parameter Description Value Units

Product A Product selected for cleaning validation study (worst case) BS Granules
AI Active ingredient in Product A Sulphamethoxazole
Product B1 Product with largest MDD (Maximum Daily Dose) value Febricol
Product B2 Product with smallest batch size Normaten Tabs (100 mg)
Detergent Active principle present in the cleaning agent Alkylbenzene Sulphonate
I Smallest strength of Product A manufactured 400.000 mg/day
J Maximum number of dosage units of product B taken/day 8.000 Units/day
K Number of dosage units per batch of final mixture of Product B1 300000.000 Units
LD50-AI Lethal Dose 50 for active ingredient in Product A 2300.000 mg/kg
LD50-Detergent Lethal Dose 50 for the detergent 437.000 mg/kg
W Average human body weight 35.000 kg
L Equipment surface area in common between Product A & B1 31627.944 cm²
R Surface area of the rinsed surface 1000.000 cm²
N Batch size of Product B2 97.500 kg
V Rinse Volume 50.000 L
SF Safety Factor * 0.001
* Give justification for using safety factor other than 0.001 in the Protocol

Summary: MACO for both AI & CA to subsequently manufactured product

MACO
Criterion
Active Ingredient Cleaning Agent
Dose 9.485 mg/L
Toxicological 0.954 mg/L 0.181 mg/L
10 ppm 0.617 mg/L 0.617 mg/L
Visual Limit 1.000 mg/L 1.200 mg/L
Copyright @ Mohammad Ovais, Pharmaceutical Scientist.