RAC Quality Systems and GMP Questions and Answers 1 — Questions and Answers
Question 1: An internal audit at a medical device manufacturer reveals that three separate production batches failed final inspection for the same dimensional specification over the past two months. The issue was documented, and the non-conforming products were scrapped each time. According to 21 CFR 820.100, which of the following actions is now required?
- Retrain all production operators on the specific inspection procedure.
- Initiate a corrective action to investigate the root cause of the failures. (Correct answer)
- Continue to monitor the trend at the next management review.
- Issue a field correction for all distributed batches.
Correct answer: Initiate a corrective action to investigate the root cause of the failures.
The recurring nature of the non-conformance indicates a systemic issue that requires a formal Corrective and Preventive Action (CAPA) investigation to find and eliminate the root cause, as required by 21 CFR 820.100. Scrapping the product is a 'correction,' but it does not prevent recurrence. Retraining may be part of a corrective action, but it should not be implemented until a root cause is identified. A field correction is not indicated as the product was not distributed.
Question 2: For a pharmaceutical product manufactured and distributed in the United States, which document provides the complete, official manufacturing history of a finished batch, including all production and control records?
- The Master Batch Record (MBR)
- The Batch Production and Control Record (BPCR) (Correct answer)
- The Drug Master File (DMF)
- The Standard Operating Procedure (SOP)
Correct answer: The Batch Production and Control Record (BPCR)
Per 21 CFR 211.188, the Batch Production and Control Record (BPCR) is the comprehensive record containing all the data and history of the manufacture of a single batch. The Master Batch Record is the approved template or recipe. A Drug Master File is a submission to the FDA containing confidential information. An SOP is a general procedure, not a batch-specific record.
Question 3: A medical device company is finalizing the development of a new infusion pump. Which of the following activities BEST satisfies the requirement for Design Validation under 21 CFR 820.30(g)?
- Simulating clinical use with intended users in a controlled environment to confirm user needs are met. (Correct answer)
- Performing software unit testing to ensure all code modules function as specified.
- Conducting performance testing on the pump's motor to confirm it meets torque specifications.
- Compiling the Device Master Record (DMR) to ensure all specifications are documented.
Correct answer: Simulating clinical use with intended users in a controlled environment to confirm user needs are met.
Design validation's purpose is to ensure the finished device conforms to defined user needs and intended uses under actual or simulated use conditions. Simulating clinical use with actual users directly tests this. Software unit testing and motor performance testing are examples of design *verification*—confirming the design output meets the design input specifications. Compiling the DMR is a documentation activity.
Question 4: During a scheduled management review, the Head of Quality presents data showing a negative trend in supplier performance, specifically an increase in late deliveries of a critical component. According to the Quality System Regulation (21 CFR 820.20), what is the MOST appropriate output of this review?
- A decision to increase the safety stock of the critical component to buffer against late deliveries.
- A note in the meeting minutes to re-evaluate the trend at the next quarterly review.
- An assignment of an action item to investigate the supplier issue and a commitment of resources to address it. (Correct answer)
- A directive to the purchasing department to immediately find a new supplier.
Correct answer: An assignment of an action item to investigate the supplier issue and a commitment of resources to address it.
Management review, as defined in 21 CFR 820.20(c), requires reviewing the suitability and effectiveness of the quality system and making decisions or assigning actions where needed. The primary role of management is to assess data and assign actions and resources to ensure the effectiveness of the quality system. Simply finding a new supplier is premature, increasing stock is a temporary fix, and waiting is not proactive.
Question 5: Under US GMP for pharmaceuticals (21 CFR Part 211), which of the following responsibilities and authorities is uniquely assigned to the Quality Control Unit (QCU)?
- Executing the process validation protocols for new equipment.
- The final disposition (approval or rejection) of all drug product batches. (Correct answer)
- Drafting and authoring all manufacturing Standard Operating Procedures (SOPs).
- Performing routine environmental monitoring of the manufacturing facility.
Correct answer: The final disposition (approval or rejection) of all drug product batches.
21 CFR 211.22 explicitly states that the Quality Control Unit shall have the responsibility and authority to approve or reject all components and drug products. While the QCU reviews and approves other documents and activities, the final authority to release or reject a batch rests solely with them.
Question 6: A pharmaceutical company implements a significant change to the manufacturing process for a commercially distributed sterile injectable drug. The change involves using a new, more efficient filtration system prior to aseptic filling. Which GMP action is required before the company can release product manufactured with the new process?
- Submitting a "Changes Being Effected in 30 Days" (CBE-30) supplement to the NDA.
- Performing a retrospective validation on the first 10 commercial batches.
- Updating the Master Batch Record and training the operators on the new filtration system.
- Completing process re-validation, including at least three successful Process Performance Qualification (PPQ) batches. (Correct answer)
Correct answer: Completing process re-validation, including at least three successful Process Performance Qualification (PPQ) batches.
A significant change to a validated manufacturing process, especially for a sterile product, requires re-validation to ensure the process remains in a state of control and produces a product of consistent quality. The FDA's guidance on process validation emphasizes a lifecycle approach, and such a change would necessitate a new process qualification stage. While a regulatory filing and document updates are also necessary, the core GMP requirement is to demonstrate through re-validation that the modified process works as intended before releasing the product.
RAC Quality Systems and GMP Questions and Answers 1
An internal audit at a medical device manufacturer reveals that three separate production batches failed final inspection for the same dimensional specification over the past two months.
The issue was documented, and the non-conforming products were scrapped each time.
According to 21 CFR 820.100, which of the following actions is now required?