Are You Ready for an FDA Inspection? Complete Inspection Guide

As part of their work, pharmaceutical companies must have their products inspected for safety and efficacy, as well as that all manufacturing meets certain regulatory standards. Of all the regulatory agencies in different countries, the Food & Drug Administration (FDA) in the United States has some of the highest standards. A successful inspection can have a major impact on a pharmaceutical company through the establishment of strong operational efficiencies, enhancement of their public image and access to a wider market.

An FDA inspection is not merely a company audit; it is an overall evaluation of the company's quality systems, documentation and compliance to current good manufacturing practices (cGMP). A pharmaceutical business must be prepared for an FDA inspection because preparation is critical to the company's success.

This article provides information to help a pharmaceutical company assess their readiness for an FDA inspection and develop strategies for the purposes of achieving success when inspected by an FDA inspector.

What is an FDA Inspection?

The FDA inspects pharmaceutical facilities to determine if they are in compliance with regulations.
Types of inspections include:

• Routine surveillance
• Pre-approval New Product
• For Cause Investigations
• Follow Up on Prior Observations

Inspectors review many different areas of the facility, including but not limited to, manufacturing processes, quality systems, documentation and employee practices.

After the inspection, the inspector may document items found during the inspection on Form FDA 483 which outlines the deficiencies noted during the inspection.

Key Areas Evaluated During FDA Inspections

1. Quality Management System (QMS)

FDA inspection teams evaluate your company’s quality management system’s adequacy.
As part of this assessment, they will examine:

• How the company manages deviations
• Corrective and preventative action
• Change control
• How it handles complaints

A solid quality management system will provide for identification, investigation and resolution of problems.

2. Documentation and Data Integrity

Documentation is an essential aspect of the FDA inspection.
Inspectors will review:

• Batch production records
• Standard operating procedures
• Log books
• Analytical data

Data must meet the ALOCA+ principles (Attributable, Legible, Contemporary, Original, Accurate) otherwise any type of deviation or missing data will create major issues.

3. Manufacturing Operations

FDA inspectors will be looking at how you perform your manufacturing actually follows (comply with) your documented approved procedures.
This will consist of evaluating:

• Use of equipment (maintenance and calibration)
• Validation/qualification of processes
• In-process controls
• Cleaning processes

Any deviation from a procedure will result in observations.

4. Facility and Equipment

The physical condition of your facility is a direct reflection of your compliance to Good Manufacturing Practice (GMP). Inspectors will look for:

• The general cleanliness and maintenance of your facility
• Qualification/maintenance of your equipment (IQ, OQ, PQ)
• Calibration records
• Your environmental controls

Poor cleanliness and/or maintenance of your facility will be viewed as having a weak quality management system.

5. Personnel and Training

Employees must be qualified to perform their roles via training.
Inspectors can examine:

• Employee Interviews
• Training Records
• Observation of Work Practices

Employees who are not properly trained and have inconsistent job practices can create compliance problems.

6. Laboratory Controls
The inspection of a QC laboratory can include:

• Validation of Analytical Methods
• Calibration of Instruments
• Sample Handling
• OOS Investigations

Laboratory data needs to be accurate and reliable and documented well.

Steps to Ensure FDA Inspection Readiness

1. Complete an Assessment of Internal Controls
Regular assessments of internal controls will allow the identification of gaps prior to an inspection by the regulators. The assessment must:

• Cover all functional areas
• Involve qualified individuals to perform the assessment
• Provide a written report of the assessment, with appropriate follow-up activities

The assessment will simulate an actual inspection and increase readiness for an inspection.

2. Keep Documentation Current

All documentation must be:

• Current and approved for use
• Easily accessible to all individuals that need to utilize the documentation
• Consistently implemented across all functional areas

A significant number of inspection findings are due to documentation that is outdated or missing.

3. Improve Data Integrity Practices

There is a strong emphasis from the FDA on data integrity.
Best practices include:

• Using electronic systems that provide an audit trail for any modifications
• Having access controls that restrict access to critical data
• Conducting regular reviews of the data for accuracy

By demonstrating that data is accurate, there is a level of confidence established that the organization is meeting regulatory requirements.

4. Ensure that Equipment is Qualified and Calibrated

All manufacturing or testing equipment must:

• Be properly qualified (IQ, OQ, PQ)
• Be calibrated on a regular basis
• Have an established maintenance schedule

If equipment is not qualified or calibrated properly or if there are no records of the equipment's calibration, there is a high likelihood that the auditor will leave an observation on your audit report.

5. Train Personnel Effectively

Training is essential for regulatory compliance. All staff will:

• Become familiar with GMP regulations
• Know their SOPs
• Be ready to respond to questions from an inspector

Doing mock interviews and updating training will give employees confidence.

6. Implementation of a Strong CAPA System

A strong Corrective Action and Preventive Action (CAPA) system is an indication of the company's ability to remedy quality-related issues. CAPA must be:

• Root-cause driven
• Completed in a timely manner
• Effective and able to be validated

If you are seeing similar issues repeatedly, this may mean that your implementation of CAPA has holes in it.

7. Prepare for Inspector Interaction

There are best practices for your interaction with inspectors during inspection readiness.
Best practices include:

• Be forthcoming and honest
• Provide complete and accurate answers to questions
• Avoid speculation and guessing

Professional communication during an inspection demonstrates the maturity of the organization.

8. Cleanliness and Organization of Facilities

A clean and well-kept facility makes a positive first impression.
The things to focus on will be:

• Well-organized work areas
• Clearly labelled items
• Clean floor and equipment

Much of what visual compliance looks like will establish the foundation for the inspection process.

Common FDA Inspection Findings

Below are some of the most likely inspection findings:

• Incomplete or inaccurate records
• Data integrity or adhere-to-correct-data issues
• The lack of appropriate investigations
• The lack of adequate training records
• Equipment maintenance issues

Proactively addressing one or more of the above-mentioned issues will decrease inspection risks.

Role of Quality Culture in Inspection Readiness

Being ready for an inspection is not only about systems; it is also about culture.
An organization with a well-established quality culture has some of these characteristics:

• Employees follow procedures consistently
• Issues are reported in a timely manner
• Continuous improvement is supported

Any organization that has a well-established quality culture will be continually inspection-ready.

What Happens After an FDA Inspection?

The outcomes of an inspection by the FDA may include:

• Issuing Form FDA 483 with findings
• Classifying the inspection as NAI, VAI or OAI.
• The issuance of a Warning Letter may be appropriate for companies with noted serious deficiencies.

Response to findings by the FDA, including corrective action taken to address findings, is required within a specified time frame.

Successful FDA preparation requires a systematic, proactive approach. To be successful, your organization needs robust quality systems, well-trained individuals, accurate records and a culture of compliance.

When pharmaceutical organizations make continuous efforts to improve such things as data integrity, correct implementation of CAPA and facility maintenance they will be ready when an inspection occurs.

In the pharmaceutical industry, being prepared for inspection is not a single event; it is a constant commitment to quality and compliance.

Frequently Asked Questions (FAQs) on FDA Inspection

Q1. What is an FDA inspection?

Answer: A facility's Resolution to a Regulatory Compliance Inspection is a process (an inspection) that a facility undergoes as part of FDA inspections to determine regulatory compliance.

Q2. What is Form FDA 483?

Answer: An FDA Form 483 is a document of comments from officials performing the inspection to document contamination and other practices that breach regulatory compliance.

Q3. What does cGMP mean?

Answer: "Current Good Manufacturing Practices" means to produce consistent products regardless of who manufactured them.

Q4. How often does the FDA inspect facilities?

Answer: FDA typically inspects a facility every two to three years based on the facility's risk factor.

Q5. What are common inspection findings?

Answer: Observations made in inspection reports by regulators are common and include: errors in records, defective data and records, inadequate CAPA systems and poor or defective equipment.

Q6. How can companies prepare for inspections?

Answer: Facility preparation for an inspection can be accomplished through the audit process by continuing to provide training to employees and having in place a good quality assurance system.

Q7. What is data integrity?

Answer: Data integrity refers to the accuracy, completeness and dependability of data.

Q8. What happens after an inspection?

Answer: After an FDA inspection, the FDA may conduct a post-inspection audit of records based on the issues observed to issues documents to issue the proper findings of noncompliance.

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