Preparing for FDA Inspections | Best Practices for Compliance

The pharmaceutical business relies heavily on inspections from a drug manufacturer’s regulatory authority, but none have the level of scrutiny from the U.S. Food and Drug Administration than any other global regulatory authority. Manufacturers that manufacture drugs must always be prepared for a routine inspection or an audit before their product can get market approval, the FDA requires that manufacturers to remain compliant with current GMPs and prepare in advance of the inspection.

There’s not a one-time way to be ready for an inspection – this takes a daily delegation to continuously improve quality, maintain sufficient systems of operation by having trained employees and create a compliant workplace environment.

This article will guide pharmaceutical companies as they prepare for inspections by the FDA as it discusses basic principles of best practices related to how manufacturers can be ready for inspections by either an FDA staff member(s) or third party audit personnel.

Understanding FDA Inspections

The mission of the FDA is to ensure compliance with specified standards for all companies in the pharmaceutical industry to produce safe products using FDA-approved ingredients. This is done through regular compliance inspections. These inspections may be initiated based on a variety of criteria including:

• Regularly scheduled inspections to ensure compliance
• Application or approval to market a new drug
• Complaint or report of an injury related to the use of a pharmaceutical product
• Re-evaluation of the compliance of a facility that has previously been inspected and/or observed to have issues or violations.

At the conclusion of a routine compliance inspection, the FDA will document its findings using Form FDA 483. If serious violations are identified, the FDA may follow up with a warning or other type of action.

Why Inspection Readiness is Critical

Being prepared for inspection is very important so that a company can prove to the FDA that they are in compliance at all times. Benefits of being prepared for inspection:

• Decreased chance of regulatory enforcement
• Shorter time to market for new products
• Improved quality and consistency of manufactured products
• Increased credibility of the organization

Organizations that continuously prepare for inspections perform better than those that prepare only at the time of expected inspection.

Core Areas Evaluated During FDA Inspections

1. Quality Management System (QMS)

The FDA heavily emphasizes effective Quality Management Systems.
Inspectors judge:

• How deviations are managed
• How the CAPA system functions
• Change control processes
• Complaints handling systems

A strong QMS shows the ability of an organization to detect, investigate and resolve quality defects.

2. Documentation and Data Integrity

Document review receives a lot of scrutiny when performing inspections.
Inspectors review:

• Batch records
• SOPs
• Analytical data
• Logbooks

All recorded data must adhere to ALCOA+ principles. Any inconsistencies in the record, missing records, or evidence of record tampering will result in significant inspection observations.

3. Manufacturing Operations

When inspecting manufacturing operations, inspectors will observe the manufacturing process to assess whether they are being conducted according to approved methods.
Inspectors will assess:

• Process validation
• Equipment operation
• In-process controls (IPC)
• Cleaning practices

If there is deviation from approved methods, there is an indication of inadequate manufacturing compliance.

4. Facilities and Equipment

Facility conditions and the condition of items of equipment provide an overall picture of the quality system.
Inspectors look at things such as:

• The level of maintenance and cleanliness of the facility
• Whether equipment is qualified (IQ, OQ and PQ)
• Calibration records on equipment
• Environmental control systems

Facility conditions that are poor will create immediate concern.

5. Personnel and Training

Personnel competency is imperative to achieving compliance.
Inspectors can accomplish the following:

• Interview operators/analysts
• Review training records
• Observe work practices

Operators/analysts must demonstrate an adequate understanding of what their functions are and how they will be conducted.

6. Laboratory Controls

QC laboratories will be evaluated based on the accuracy and reliability of their outcomes.
Inspectors will evaluate the following items:

• Analytical Procedures
• Calibration Standards
• Sample Handling
• Investigations of Out of Specifications

QC laboratory data - must be complete, accurate and traceable.

Best Practices for FDA Inspection Readiness

1. Create an Effective Culture of Quality

The enforcement begins with culture.
Creating a culture of quality will enable:

• Employees will consistently execute procedures according to established methods.
• Employees will report any nonconformance issues without fear of retribution.
• Employees will have the means and be encouraged to improve their work.

Leaders are critical to establishing this culture within the organization.

2. Perform Regular Internal Audits

Internal audits are a tool to identify nonconformance before regulatory authorities do.
All routine/regular internal audits should:

• Cover all departments in the organization.
• Only be conducted by trained individuals.
• Include appropriate CAPAs in the report.

Mock audits can help organizations experience what a real FDA audit would be like and help the organization be prepared.

3. Maintain Accurate and Updated Documentation

Documentation must:

• Always be approved and current.
• Always be readily available to be referenced.
• Consistently followed by employees in daily execution of work.

Some common examples are old and/or out-of-date SOPs, incomplete records, no signatures, etc.

4. Strengthen Data Integrity Systems

The FDA continues to investigate the requirement that companies follow data integrity as part of their compliance obligations. Organizations should implement the following best practices:

• Use validated electronic systems.
• Maintain audit trails on all data entries.
• Controlled access to validated electronic systems.
• Regularly review and validate data over time.

Reliability of data establishes trust with applicable regulatory authorities.

5. Ensure Equipment Qualification and Maintenance

All equipment, including computers and other automated systems must be:

• Qualified (IQ, OQ, PQ).
• Calibrated on a scheduled basis.
• In good condition when in use.

Commonly found during inspections is incomplete records for equipment, overdue calibrations.

6. Implement an Effective CAPA System

A strong CAPA system shows the organization’s ability to resolve problems.
The CAPA system should:

• Be rooted in root cause analysis
• Implement changes promptly
• Effectively confirm that the implemented changes worked

If there is a chronic problem in your business, it could be a sign that your CAPA system is weak.

7. Train Personnel Continuously

Training is paramount to being ready for an inspection.
Employees need to:

• Understand GMP requirements
• Know SOPs
• Be well prepared to answer questions from inspectors

Mock interviews or other refresher training can give employees extra confidence when being inspected.

8. Prepare for Inspector Interaction

The way employees communicate/interact with inspectors is important.
Some best practices for interacting with inspectors include:

• Having honesty and transparency
• Answering all questions directly and accurately
• Providing only information that is relevant to the question being asked
• Not guessing or speculating

The example of employees being professional will create a better impression from the inspector.

9. Maintain Facility Cleanliness and Organization

A clean and orderly facility indicates compliance.
During an inspection, an inspector will notice:

• Housekeeping practices
• The cleanliness of equipment
• The labeling and storage of materials

Visual compliance can often create the environment in which the inspection takes place.

10. Review of Prior Inspection Results

Prior inspection results have been very informative.
Companies should:

• Consider any previous 483's issued by the FDA
• Confirm that all CAPA actions related to the issued 483s have been addressed
• Confirm that all measures implemented for the prior 483s were successful

If you do not address any previous findings, they may be noted again.

11. Implement Risk-Based Approach

Utilizing this method enables priority for the most critical aspects. Utilizing guidelines (from the ICH Q9: Quality Risk Management) would provide a basis for risk assessment.
Emphasis should be placed on:

• Processes with the highest risk
• Critical equipment
• Key quality attributes

12. Develop an Inspection Management Team

An organized inspection team allows for better coordination of activities.
This team will:

• Provide guide and direction to the inspector whilst travelling through the facility.
• Manage requests for documentation and information.
• Organize and manage the response process.

This type of coordination minimizes confusion and delays.

Common Mistakes to Avoid

There are a number of mistakes that too many companies make when being inspected by an FDA inspector. These are:

• Not having complete and accurate documentation
• Taking too long to respond to an Inspector's questions
• Having employees who do not know how to do their jobs
• Not controlling your documents
• Trying to hide from issues instead of fixing them.

If a company avoids the mistakes listed above, it will have better inspection results.

What Happens After the Inspection?

After the FDA inspects a company, it may:

• Provide the company with an FDA Form 483 that contains observations about the company’s processes
• Determine whether the company received a "No Action Indicated (NAI)", or "Voluntary Action Indicated (VAI)" or "Official Action Indicated" (OAI) as a result of the inspection
• Send warning letters if serious conditions were found.

Companies must also respond to the observations listed on the FDA Form 483 within the timeframe specified and include an Action Plan for each observation.

Maintain Continuous Inspection Readiness

Building a process to have constant readiness for inspections should not be a last-minute task.
Your organization should:

• Regularly monitor quality metrics
• Conduct periodic evaluations
• Make changes to procedures when necessary
• Continuously train new employees and upgrade technology

Successful maintenance of continual readiness will allow the company to always be ready for an inspection.

To be ready for an FDA Inspection requires a proactive, structured and disciplined approach. It involves a strong Quality System with accurate documentation, trained personnel and a compliant culture.

Implementing best practices in the areas of internally auditing your system, having an effective CAPA System, having strong data integrity controls and continuing to train your employees will allow pharmaceutical companies to confidently prepare for an Inspection as well as achieve the desired outcome.

In the heavily regulated environment in which the pharmaceutical industry operates, Being Inspection Ready is much more than just passing an Audit; it is about delivering quality products, ensuring patient safety and being successful in the future.

Frequently Asked Questions (FAQs) on FDA inspection

Q1. What is an FDA Inspection?

Answer: An assessment of compliance with applicable laws and regulations.

Q2. What is Form FDA 483?

Answer: A written list of things observed during an inspection.

Q3. What is cGMP?

Answer: Good manufacturing practices (cGMP) are rules that make sure that manufactured items are consistently of good quality.

Q4. How can companies prepare for inspections?

Answer: Do audits, train employees and have solid quality systems.

Q5. Common findings of inspection.

Answer: Document problems, problems related to data integrity and inadequate CAPA systems.

Q6. Why is data integrity significant?

Answer: To allow verification of record accuracy and reliability.

Q7. How Check the Dates of Inspection?

Answer: Inspections are completed approximately every 2 to 3 years based on a risk assessment.

Q8. What happens After Inspection?

Answer: Results may be issued as a written observation and necessitate a corrective action plan.

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