US FDA Audit in QC: How to Make A Strategy

Introduction and Outcome: US FDA Audit

Getting USFDA audit clearance is one of the most challenging tasks for any pharmaceutical company. However, the fact is that no company sells its pharmaceuticals in the United States without approval. It requires strategic planning and compliance related to processes, systems, documentation, and according to current Good Manufacturing Practices (cGMP) That is why I decided to share my skill-based knowledge on this topic. In this article, I will discuss how to create a strategy-based checklist for a US FDA audit in QC department

US FDA Audit Checklist

Review and readiness of the following checklist are required to get approval for US FDA Audit in QC:

Documentation and Record Keeping
Personnel and Training
Laboratory Equipment and Instrumentation
Laboratory Environment
Sampling and Testing Procedures
Quality Control Procedures and Compliance
Internal Audits and Self-Inspection
FDA Interaction and Coordination
Review of Regulatory Requirements

Documentation and Record Keeping

Review SOPs (Standard Operating Procedures):
- Ensure that all QC-related SOPs are up-to-date, accurate, and compliant with cGMP standards.
- Verify that SOPs are readily accessible to auditors and staff.
Test Methods and Protocols:
- Ensure that all QC test methods (e.g., analytical methods, microbiological methods) are validated and the documentation is complete.
- Ensure that the methods used are current and reflect the latest compendial standards.
Batch Records:
- Ensure all batch records are complete, accurate, and include all QC test results.
- Ensure that test records (e.g., raw data, chromatography results, lab notebook entries) are signed and dated by responsible personnel.
Raw Data:
- Ensure raw data (e.g., analytical instruments printouts, calculations) are retained and legible.
- Ensure electronic data is secure and backed up with appropriate access control mechanisms.
Change Control Documentation:
- Ensure change control processes are followed and documented, including any changes to QC methods, equipment, or processes.
Stability Data:
- Ensure stability testing and data are current and properly documented for marketed products.

Personnel and Training

Training Records:
- Ensure all QC staff are trained in current SOPs, cGMPs, and relevant regulatory requirements.
- Verify that records of all training activities are up-to-date and complete.
Competency Assessments:
- Ensure staff competency evaluations are conducted periodically for all QC personnel.
Qualifications for Analysts:
- Ensure that analysts performing testing are qualified and have the appropriate education, experience, and training.

Laboratory Equipment and Instrumentation

Calibration and Qualification:
- Ensure that all QC instruments and equipment (e.g., HPLC, GC, balances, pH meters) are calibrated, qualified, and in good working condition.
- Verify that calibration certificates are available and up to date.
Maintenance and Service Records:
- Ensure all equipment maintenance and service records are complete and accessible.
- Verify that preventive maintenance schedules are adhered to.
Equipment Logbooks:
- Ensure that equipment logbooks are accurately maintained with details of use, maintenance, and calibration activities.
Software Validation:
- Ensure that software systems (e.g., LIMS, chromatography software) are validated, with documented evidence of validation activities.

Laboratory Environment

Facility Condition:
- Ensure that the laboratory and associated areas (e.g., stability chambers, controlled environments) are clean, organized, and free from contamination.
Environmental Controls:
- Ensure that environmental monitoring procedures (e.g., temperature, humidity, particulate matter) are in place and the data is available.
- Verify that storage conditions for raw materials, intermediates, and finished products are in compliance with specifications.
Contamination Control:
- Ensure that contamination control measures are in place (e.g., cleanroom practices, gowning procedures).
- Verify that procedures for handling out-of-specification (OOS) results, cross-contamination, and sample integrity are documented and followed.

Sampling and Testing Procedures

Sampling Plans:
- Ensure that sample collection, storage, and testing procedures are defined and followed.
Test Result Documentation:
- Ensure that test results are documented properly with appropriate signatures, dates, and explanations for any deviations or out-of-specification results.
OOS (Out-of-Specification) Results:
- Ensure there is a defined procedure for investigating OOS results and that these investigations are fully documented.
- Verify that OOS investigations follow root cause analysis principles and include corrective actions.
Microbiological Testing:
- Ensure microbial testing, if applicable, is performed in accordance with USP or other relevant pharmacopoeial guidelines.
- Verify that appropriate aseptic techniques are used in microbiological testing.

Quality Control Procedures and Compliance

Change Control and CAPA:
- Ensure that any changes to QC procedures, equipment, or testing protocols are documented through formal change control.
- Ensure that Corrective and Preventive Actions (CAPA) are documented and implemented in response to non-conformances.
Specifications and Test Methods:
- Ensure that all test methods, specifications, and acceptance criteria are well-documented and updated as necessary.
- Verify that the test methods used align with the product specifications and regulatory requirements.
Compliance with cGMP:
- Ensure that all QC practices comply with current Good Manufacturing Practices (cGMP).
- Verify that QC documentation and testing procedures meet FDA guidelines and expectations.
Validation and Qualification:
- Ensure that any QC processes that require validation (e.g., method validation, cleaning validation) are documented and completed.
Product Release and Approval:
- Verify that the process for product release, including review of QC test results, is well-documented.
- Ensure that all release decisions are made by qualified personnel and based on validated test results.

Internal Audits and Self-Inspection

Internal Audits:
- Ensure that internal audits are performed regularly to assess compliance with SOPs and regulatory requirements.
- Ensure that audit findings are addressed with corrective actions and preventive actions (CAPA).
Self-Inspection Reports:
- Ensure that self-inspection reports are prepared and reviewed regularly for ongoing compliance with cGMP.
- Ensure that any deficiencies identified are documented and rectified before the FDA audit.

FDA Interaction and Coordination

Audit Readiness:
- Designate a team or person responsible for interacting with the FDA auditors during the audit.
- Review the roles and responsibilities of the QC team during the audit, and ensure they are clear on procedures.
Documentation Organization:
- Ensure that all relevant documents (e.g., batch records, test results, equipment qualifications, SOPs) are organized and easy to access for the auditors.
Prepare for Interview/Questioning:
- Prepare QC personnel for potential questions regarding processes, documentation, training, and compliance.
Audit Log:
- Maintain a log of any FDA audit findings and responses, including timelines for addressing any deficiencies or observations.
Corrective Actions:
- Have a plan in place for implementing corrective actions if the auditors identify any deficiencies during the audit.

Review of Regulatory Requirements

FDA Guidance:
- Review the most current FDA guidance documents related to QC and cGMP compliance for your industry (e.g., drugs, biologics, medical devices).
Compliance with FDA 21 CFR:
- Ensure compliance with relevant parts of Title 21 of the Code of Federal Regulations (CFR), particularly 21 CFR Part 210, Part 211, and Part 820 (for medical devices).
Inspection Readiness:
- Familiarize the team with the FDA’s inspection process, including the Inspectional Observations (Form 483), warning letters, and other regulatory actions.

Conclusion

I hope this article has helped you learn how to create a strategy-based checklist for a US FDA audit in QC.

You may also want to check out other articles on my blog, such as:

FAQs

What is the US FDA audit?

The USFDA audit refers to an inspection or evaluation conducted by the U.S. Food and Drug Administration (FDA) to assess whether a company or facility is complying with FDA regulations and standards. These audits are typically carried out to ensure that products such as drugs, medical devices, food, and cosmetics are being manufactured, stored, and distributed safely and in accordance with the law.
There are different types of FDA audits, including:
Good Manufacturing Practice (GMP) Inspections: These audits ensure that manufacturers are adhering to GMP guidelines to ensure the quality, safety, and efficacy of products.
Pre-Approval Inspections (PAIs): These are conducted before a new drug or product can be approved for market sale. The FDA checks that the manufacturing process and facilities meet regulatory requirements.
Routine Inspections: Regular inspections of facilities that are already approved to monitor ongoing compliance with FDA regulations.
For-Cause Inspections: These audits are initiated when the FDA has concerns about a specific company or product, often based on reports of adverse events or violations.
Follow-Up Inspections: These audits occur after previous inspections to verify that any violations or issues have been corrected.
During the audit, the FDA inspectors review records, facilities, manufacturing processes, equipment, and procedures, and may take samples for testing. If violations are found, the company may be required to make corrective actions or face penalties, including product recalls or sanctions.

What is quality control FDA?

Quality control (QC) in the context of the FDA (U.S. Food and Drug Administration) refers to the processes and procedures used by pharmaceutical and other regulated industries to ensure that their products meet specific standards of safety, effectiveness, quality, and consistency before they reach the market.
The FDA oversees and enforces regulations that require manufacturers to implement rigorous QC systems. These systems help ensure that products, especially drugs, medical devices, and food, are:
Safe for consumers: Products should not cause harm when used as intended.
Effective: Products must perform as promised in labeling and marketing.
Consistent: Products should be manufactured with uniform quality from batch to batch.
Compliant with regulatory standards: Products must meet all applicable FDA regulations and guidelines, including Good Manufacturing Practices (GMP).
Quality control in FDA-regulated industries typically includes:
Testing of raw materials: To ensure ingredients meet specified quality standards.
In-process testing: To monitor quality during production.
Final product testing: To ensure the product meets all specifications before release.
Recordkeeping and documentation: To provide a clear audit trail of testing and decisions.
Compliance with standards: Following FDA guidelines such as Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP), and Good Clinical Practices (GCP).

What is a QMS FDA?

A QMS FDA refers to a Quality Management System (QMS) that complies with the standards and regulations set forth by the U.S. Food and Drug Administration (FDA). This system is particularly relevant for companies involved in the development, manufacturing, and distribution of medical devices, pharmaceuticals, food, and other FDA-regulated products.
The FDA requires these companies to establish and maintain a QMS to ensure that their products are consistently produced and controlled to meet quality standards. For medical devices, the QMS is typically guided by 21 CFR Part 820, which outlines the FDA’s requirements for quality systems, including:
Design Controls
Production and Process Controls
Corrective and Preventive Actions (CAPA)
Document Control
Purchasing Controls
Complaint Handling
Internal Audits
The goal of a QMS FDA is to ensure product safety, efficacy, and compliance with regulatory requirements, thereby minimizing risks to consumers and ensuring high-quality products.

Reference:

Inspection classification