Equipment Name: Example Determination of Acceptance Criteria for

Add Company Name/Logo Here

Location: Tabletting Block Cleaning Validation (CV) Studies
Compiled By: Ovais ORAL PRODUCTS Date 2/7/2007

INSTRUCTIONS:
Sampling Method Swab Sampling Fill in the Coral input fields as mentioned (read the
comments if needed)

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 (Maximum Daily Dose) 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 B1 taken/day 16.000 Units/day
K Number of dosage units per batch of final mixture of Product B 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 & B 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 CV Protocol

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

MACO 1.0
Criterion
Active Ingredient Cleaning Agent

Limit (mg/25cm²)
0.8
Dose 37.500 mg/25 cm²
Toxicological 1.943 mg/25 cm² 0.630 mg/25 cm² 0.5
10 ppm 0.750 mg/25 cm² 0.750 mg/25 cm²
0.3
Visual Limit 1.000 mg/25 cm² 1.200 mg/25 cm²
0.0
Dose Tox. 10 ppm
Visual
Criterion

Criterion

Formulas used for calculation:

This spreadsheet may not be resold or distributed. Please request
author (mohammad@xepasp.com for any changes required to be
made).
 This spreadsheet may not be resold or distributed. Please request
author (mohammad@xepasp.com for any changes required to be
A) Dose criterion (0.001)
made).

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 ingredien
J = Maximum number of dosage units of Product B1 taken/day
K = Number of dosage units per batch of final mixture of Product B1
L = Equipment surface area in common between Product A & B1/B2 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 B1 taken/day
K = Number of dosage units per batch of final mixture of Product B1
L = Equipment surface area in common between Product A & B1/B2 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 B2
N = Number of kgs per batch of final mixture of Product B2
L = Equipment surface area in common between Product A & B1/B2 expressed as cm²
U = Swab area (25 cm²/swab)

Reference: Fourman, G.L. and Mullen, M.V., "Determining Cleaning Validation Acceptance Limits for Pharmaceutical Manufacturing Operatio
© 2009 Mohammad Ovais v1.1
Pharmaceutical Scientist
ve ingredient

g Operations," Pharm. Technol. 17(4), 54-60 (1993).

Equipment Name: Example Determination of Acceptance Criteria for
Add Company Name/Logo Here
Location: Tabletting Block Cleaning Validation (CV) 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) Product No. 5
AI Active ingredient in Product A Mefenamic Acid
Product B1 Product with largest MDD (Maximum Daily Dose) value Product No. 1
Product B2 Product with smallest batch size Ciprofloxacin HcL Tablet
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 B1 taken/day 8.000 Units/day
K Number of dosage units per batch of final mixture of Product B 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 & B 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 CV Protocol

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

MACO 1.0
Criterion
Active Ingredient Cleaning Agent

Limit (mg/25cm²)
0.8
Dose 9.485 mg/L
0.5
Toxicological 0.954 mg/L 0.181 mg/L
10 ppm 0.617 mg/L 0.617 mg/L 0.3
Visual Limit 1.000 mg/L 1.200 mg/L 0.0
Dose Tox. 10 ppm
Visual
Criterion

Criterion
© 2009 Mohammad Ovais v1.1
Pharmaceutical Scientist