Part-I: Ensuring ANVISA Compliance: A Practical Q&A Handbook

This is Part I of a two-part series. Below is a detailed set of potential questions and answers for an ANVISA audit. These Q&A can serve as a guide for comprehensive five-day audit preparation

Periodic Product Review

1. Q: What does your Periodic Product Review (PPR) procedure entail?

A: Our PPR includes a comprehensive evaluation of batch records, deviations, complaints, stability results, and trends in critical quality attributes. It ensures ongoing product quality and identifies opportunities for improvement. The review is conducted annually per ANVISA requirements.

2. Q: How do you handle trends identified during PPR?

• A: Trends are documented and analyzed. If deviations or OOS patterns are observed, corrective and preventive actions (CAPAs) are implemented. Results are escalated to senior management.

Computer Systems

3. Q: How do you validate your computer systems?

• A: All GxP-relevant systems undergo validation as per our Computer System Validation (CSV) SOP. Validation includes user requirements, IQ, OQ, PQ, and periodic revalidation. Systems comply with ANVISA Resolution RDC 301/2019.

4. Q: How do you ensure data integrity in computer systems?

• A: Our systems follow ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate). Audit trails are enabled, and regular reviews are conducted.

Engineering and Utilities

5. Q: What is your maintenance program for critical utilities?

• A: Critical utilities like purified water, steam, and compressed air are maintained per a preventive maintenance schedule. Calibration and testing are performed periodically, and records are retained.

6. Q: How do you ensure the reliability of HVAC systems?

• A: HVAC systems are qualified with DQ, IQ, OQ, and PQ. Filters are replaced as per schedule, and pressure differentials are monitored continuously.

Air Treatment Systems

7. Q: How do you ensure the air quality in production areas?

• A: Our air handling units (AHUs) are validated to meet ISO 14644 standards for cleanrooms. We monitor particulate counts, pressure differentials, temperature, and humidity daily.
• 8. Q: What is your procedure for filter integrity testing?

• A: HEPA filters undergo integrity testing during installation and annually thereafter. Results are documented and reviewed.

Utilities

9. Q: How do you monitor the quality of utilities used in production?

• A: Utilities like purified water and steam are monitored for compliance with pharmacopeial standards (e.g., USP, Ph. Eur.). Routine tests include TOC, conductivity, and microbial limits.

Production

10. Q: How are production deviations handled?

• A: Deviations are logged and investigated according to our Deviation Handling SOP. CAPAs are defined and tracked until closure, and effectiveness checks are performed.

11. Q: How do you ensure batch traceability?

• A: Batch traceability is maintained through detailed batch records, including raw material lot numbers, processing parameters, and packaging details.

Warehouse

12. Q: How do you ensure proper storage of materials?

• A: Materials are stored in controlled environments (e.g., temperature, humidity) per their specifications. Storage conditions are monitored 24/7 with alarms for deviations.

13. Q: How is FIFO/FEFO implemented?

• A: Materials are issued based on First-In-First-Out (FIFO) or First-Expiry-First-Out (FEFO) principles to ensure quality and compliance.

Change Control

14. Q: What is your procedure for managing changes?

• A: Changes are assessed for risk and impact under our Change Control SOP. Major changes are reviewed and approved by the Change Control Committee.

15. Q: How do you handle regulatory filings for changes?

• A: Significant changes are reported to ANVISA as per regulatory requirements, and approvals are obtained before implementation.

Handling of Process Deviations

16. Q: How do you classify process deviations?

• A: Deviations are classified as minor, major, or critical based on their potential impact on product quality, safety, and compliance.

17. Q: Can you provide an example of a critical deviation and its resolution?

• A: [Example specific to the site]. For instance, a critical deviation in temperature during drying was addressed by immediate investigation, rework of the batch, and updating SOPs

Validation Master Plan

18. Q: What does your Validation Master Plan (VMP) include?

• A: The VMP outlines our validation approach for equipment, processes, cleaning, and computer systems. It includes timelines, responsibilities, and acceptance criteria.

Cleaning Validation

19. Q: How do you ensure cleaning effectiveness?

• A: Cleaning validation uses a matrix approach for multi-product equipment. Residues are tested using validated analytical methods.

20. Q: What are your acceptance criteria for cleaning validation?

• A: Acceptance criteria include limits for carryover based on toxicological evaluations (e.g., PDE limits).

Process Validation

21. Q: What is your process validation strategy?

• A: Process validation follows a lifecycle approach (Process Design, Process Qualification, Continued Process Verification). Data from three consecutive batches is used to demonstrate consistency.

OOS Procedure

22. Q: How are OOS results investigated?

• A: OOS investigations follow a two-phase approach: initial laboratory investigation and full-scale investigation if necessary. Root causes are identified, and CAPAs are implemented.

Retention Samples Management

23. Q: How do you manage retention samples?

• A: Retention samples are stored under labeled conditions matching the marketed product. They are retained for one year after expiry.

24. Q: How often are retention samples reviewed?

• A: Retention samples are periodically reviewed for integrity and compliance with the stability program.

Stability Studies

25. Q: What is your stability testing program?

• A: Stability studies are conducted as per ICH guidelines (accelerated, intermediate, long-term). Testing includes assay, dissolution, and impurity profiling.

26. Q: How do you handle out-of-trend (OOT) results in stability studies?

• A: OOT results trigger a detailed investigation. Impact assessments are conducted to determine potential implications for marketed products.