Page 1 of 1 Exercise 11 Your company manufactures and packs Theolin® 300 mg. Theolin® 300 mg is an uncoated tablet which contains 300 mg theophylline. Upon packing of batch 15B3 one of...

refer to PDF attached for exercise 11 and exercise 12


Page 1 of 1 Exercise 11 Your company manufactures and packs Theolin® 300 mg. Theolin® 300 mg is an uncoated tablet which contains 300 mg theophylline. Upon packing of batch 15B3 one of the operators noticed that there is a foreign tablet in one of the blister packs. Use the Fishbone diagram tool and 5 Why’s tool together with the following information to identify the possible root causes. Then select the three most probable root causes (where exactly did the Ibuspec tablet came from?) and to suggest possible corrective and preventative actions for each of the three most probable root causes (CAPA’s). (17) Submit ONLY your fishbone diagram and the three most probable root causes with their CAPA’s (no long discussions). State exactly where the Ibuspec tablet which ended up in the Theolin blister could have come from. • The foreign tablet was identified as Ibuspec® 250 mg which is a coated tablet used for pain and inflammation. The tablet found in the blister was however an uncoated tablet. • Batch 15B3 of Theolin® 300 mg was granulated in the same granulation cubicle as Ibuspec® 250 mg. Theolin® 300 mg was granulated first, the room was cleaned and Ibuspec® 250 mg was granulated after the cleaning. • Ibuspec® 250 mg is not compressed on the same compression machine as Theolin® 300 mg due to the fact that the Ibuspec® 250 mg tooling does not fit on the compression machine used for the compression of Theolin® 300 mg. • A batch of Ibuspec® 250 mg was compressed at the same time (compression started on the same day) as Theolin® 300 mg (batch 15B3). The batch size of Ibuspec® 250 mg is smaller than that of Theolin® 300 mg, therefore the batch of Ibuspec® 250 mg finished compression one day before the Theolin® 300 mg compression finished. • The batch of Ibuspec® 250 mg was coated directly after compression and the batch spent only 1 hour in the holding area of the coating department. • After compression of Theolin® 300 mg (batch 15B3) the batch went to the holding area in the packaging department. Packaging of this batch only started two days later, because operators were still busy on the packing line with the packaging of Lopmide® capsule. • The batch of Ibuspec® 250 mg was scheduled for packaging after Theolin® 300 mg (batch 15B3) • The company has only one wash bay for the whole production area (loose items from the weighing, granulation, compression & encapsulation, coating and packaging areas are moved to the wash bay for cleaning. Fixed equipment such as granulators, compression machines etc. are cleaned in the respective granulation, compression areas etc.). • All utensils, equipment, drums, compression/encapsulation tooling and holding containers are cleaned between different products and are stored in a separate room for clean equipment. All the operators have access to this room and fetch equipment and containers from there as and when necessary. The bulk holding containers are lined with a plastic bag before using them to store uncoated tablets (prior to coating), uncoated tablets (prior to packaging), coated tablets (prior to packaging) and capsules (prior to packaging). • At the time that this incidence occurred, the company had a shortage of plastic bags and bulk holding containers. • All the production areas are clearly separated/demarcated. Exercise 11: Schematic presentation of events * Blister of batch 15B3 Theolin with one foreign tablet (Ibuspec) Storage & Distribution Storage & Distribution Inspection & Release Day 10 Blistering of Ibuspec Day 9 Inspection * Cleaning of blister line Cleaning of blister line Day 8 Blistering of Theolin Day 6 & 7 Packaging holding area (2 days) Packaging holding area Day 5 Day 4 Compression Room 2 Theolin (compression ended day 5) Coating area Coating of Ibuspec Holding area of coating room (1 hour) Compression Room 1 Ibuspec (compression ended day 4) Day 3 Ibuspec 250 mg Day 2 Cleaning of room Day 1 Theolin 300 mg Cl ea ni ng o f b lis te r l in e Gr an ul at io n ro om 1 Page 1 of 1 Exercise 12 Consider the following situation. Make use of FMEA to evaluate the risk to the patients and the company. (20) Your company manufactures Eplic® capsules. Eplic ® is used for the treatment and control of epilepsy. The capsule is an orange opaque capsule which contains 80 mg of active and should be taken twice daily with meals to control and prevent epileptic fits. Multiple customer complaints of empty capsules were received. Lot A12B was fully distributed in South Africa and no product remains within company control. There is no evidence of tampering. Upon review of the batch record it was found that a loose dosator pin was replaced on the encapsulation machine. Following replacement and prior to resuming encapsulation, acceptance testing of capsules produced required by Standard Operating Procedure was performed and product met requirements. Further investigation revealed that the loose dosator caused empty capsules to be produced. The encapsulation system utilized a vacuum system to remove empty capsules. This empty capsule removal system includes a reservoir for holding empty capsules rejected during the manufacturing process. As a result of the loose dosator, an atypically high number of reject empty/low fill capsules were produced during the encapsulation operation, causing the reservoir to be filled and eventually overflow. The reservoir was physically located over the acceptable capsule flow. Therefore, it was determined during the investigation that if the empty capsule chamber overflowed, there was potential for rejected capsules fall back into the acceptable capsule exit chute and be reintroduced to the lot. Sealed bottles were obtained from retained samples of the lot. Of 310 capsules examined, 31 empty and 3 low fill weight capsules were found. Between one and three empty capsules were found in 15% of the bottles which were evaluated. Risk Question: Does a small number of potential low fill or empty capsules in a single batch of Eplic® capsules pose an unacceptable risk to (i) patients, and (ii) to the company? Perform a Failure Mode and Effects Analysis (FMEA) risk assessment to determine the risks