Validation of cleaning procedures in the manufacture of different tablets in shared facility (Diclofenac Potassium, Ibuprofen and Olanzapine)‎

Other Title(s)

التثبت من فعالية إجراءات التنظيف لماكنات التصنيع المشتركة في إنتاج الحبوب للمستحضرات ذات الفعالية المختلفة

Dissertant

Sayigh, Aman Salamah

Thesis advisor

Qanazi, Firas I.
Kharuaf, Mahir

University

Birzeit University

Faculty

Faculty of Pharmacy, Nursing and Health Professions

University Country

Palestine (West Bank)

Degree

Master

Degree Date

2018

English Abstract

Diclofenac Potassium 50 mg, Ibuprofen 200 - 600 mg and Olanzapine 2.5 - 20 mg tablets were manufactured in a multi-product facility, where Diclofenac Potassium, Ibuprofen and Olanzapine could be possible cross-contaminants, may alter the safety, identity, strength, quality and purity of the subsequent drug product beyond the established requirements.

Validation of cleaning processes provides documented evidence that the approved cleaning procedure will consistently provide clean equipment suitable for subsequent product processing.

To achieve that, the worst-case product (using potency, cleanability and solubility criteria), difficult to clean locations of each equipment and the sampling methods(swab or rinse) for each sampling location were determined, in addition the acceptable limits for API residue was calculated, and an analytical method for estimation of the worst-case product was developed and validated.

Simulation study using coupons from both sampling procedures and the surface of the equipment was accomplished.

Finally, one batch of the worst-case product was manufactured and cleaned using the suggested procedures, and then the worst-case samples were analyzed to verify the effectiveness of the cleaning procedure for removal of product residues and cleaning agents to acceptable limits.

Cleaned Equipment hold time (CEHT) was determined to control the potential of microbiological contaminants before equipment reuse or re cleaning.

Olanzapine tablets were the worst-case over the other products, since it had risk in its solubility and in pharmacology or potency.

The maximum allowable Olanzapine residue from the previous product using swab technique must be below 0.2273 ppm/ swab of 5 cm x 5 cm, while the acceptance criteria for Olanzapine residue using rinse technique for Bin Mixer, Tablet Press Punches and Dies and for Coating Pan equipment were 0.45453 ppm, 0.020980 ppm, 0.031817 ppm, 0.62489 ppm, respectively.

The average recovery for swab technique was found to be 76.73%, while it was 102.98% and 102.99% for rinse technique for Bin Mixer and Coating Pan, respectively.

According to soak technique for Tablet Press Punches and Dies, the average recoveries were 89.03% and 89.19%, respectively.

So depending on WHO _TRS_937 guidelines, the sampling technique is considered good.

Pilot scale Olanzapine Tablets were manufactured on SDI equipment, and cleaned using the suggested cleaning procedure.

In addition, CEHT was studied for eleven days, giving good results for microbiological contamination during the period.

The analytical results insure with documented evidence that the used cleaning procedure for the equipment, reduce the residues of the worst-case Olanzapine product and cleaning agent (15% SLS) from the equipment contact surface to acceptable limits and leave the equipment safe for manufacturing the subsequent product.

Main Subjects

Public Health

Topics

• Industrialization
• Machines
• Sterilizing

No. of Pages

184

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-957645