How to Get Your Organization Prepared for an FDA Inspection


FDA inspections are a natural part of any pharmaceutical manufacturing organization’s on-going business.  They’re conducted to ensure the safety and efficacy of manufactured drugs, as well as to ensure that companies comply with current Good Manufacturing Practices (cGMP).

According to the FDA, it can only approve an ANDA (Abbreviated New Drug Application) or NDA (New Drug Application) only “if the methods, facilities and controls used for the manufacture, processing and testing of the drug are found adequate to ensure and preserve its identity, strength, quality, and purity.”

This article provides insight and tips to help successfully pass FDA inspections.

So Why are Inspections Held?

Inspections are performed for cause, such as prior approval inspections (PAI) for a new product, or on a regular cycle, typically every two years.  While cGMP compliance is not statutorily required, for a contract manufacturing organization (CMO) like PCI Synthesis, it’s a primary expectation of our sponsors, and therefore essential to our continued growth and reputation in the industry.

The types of organizations that must pass FDA inspections, include:

  • Finished dosage manufacturers
  • API manufacturers
  • Finished dosage and API testing sites
  • Primary packaging and labeling sites
  • For animal derived APIs, the facility that performs the crude extraction

While typically held every two years, the main reasons for FDA inspections involve new facilities, or new or existing processes for products, such as new APIs.  Inspections will also be required once the first application is filed by the applicant or for new molecular entities.

Sign up for our Blog Subscription and get the latest News and Insight right in your inbox

If an inspection is determined to be needed, the FDA will send a team of individuals to conduct the inspection. The team may include: investigators, other specialists, chemistry experts, microbiology experts, a process/facility expert and a formulation expert.

Where are Inspections Held?

The FDA conducts inspections of facilities all over the world, and essentially any facility that intends to either ship or market drug substances or drug products to the US.  Foreign facilities that fail inspections can cause problems for U.S.-based sponsors. For example, a company came to us once when their Indian CMO failed inspection; they asked us to pick up the project.  Unfortunately, their Reference Listed Drug (RLD) expired before we could have delivered new material.  Unfortunately, to ensure FDA approval, the company had to start the process over again. It’s important to note that the FDA inspections are the same whether inside the U.S. or outside.

Ready for Inspection

Once an application is submitted to the center, the firm and all facilities mentioned are considered by the FDA to be ready for inspection. The inspection team will determine if the site is ready for commercial manufacturing, the information submitted is consistent with site records and that it is complete and accurate. It also will review sampling plans, testing of components and evaluate the facility and equipment procedures with a focus on contamination controls.

As part of FDA inspections, the quality system for batch release will be evaluated.  Inspectors will focus on laboratory system Standard Operating Procedures (SOPs); personnel; training and stability data; as well as evaluate test methods and impurity profiles.

Preparing for FDA Inspections

While CMOs and sponsors need to prepare for inspections, it can’t be a last-minute, one-time thing. Preparing for FDA inspections involves a long-term and sustained commitment to devote the resources necessary for success. It’s important to operate each day to remain in compliance to FDA standards; and one of the more important jobs is to keep on top of changing regulations since those can evolve after your project started. Your resources should be deployed in three essential activities: Internal Auditing, Training, and Data Analysis.

Internal auditing.  This involves thorough self-assessments including routine facility and personnel behavioral audits, or in-depth critical reviews of key systems, such as preventative maintenance, customer complaints or deviation investigations.  Additionally, comprehensive process surveys identify areas for improvement that can be addressed in advance and help ensure a successful regulatory inspection.

These audits can be performed by company personnel, but are often more productive when they involve an independent consultant who can see things from a different perspective and offer new ideas.

Training.  Personnel training can empower your employees to increase their knowledge and awareness of the activities they perform. For thorough training plans, a routine gap assessment is essential to measure each person’s level of current training against a predetermined standard or matrix of responsibilities.  Training sessions also can encourage employees to offer suggestions for improvements to the systems they use and support.

Data Analysis.  Finally, regular data analysis from quality systems is critical to identify trends and find and correct hidden or subtle systemic weakness.  For this to be effective, a company must first identify quantifiable metrics or key performance indicators (KPI) for its critical systems and processes. Then, by properly responding to the data with meaningful corrective actions, a company can build genuine confidence that its quality system is prepared for an FDA inspection.

It’s important to have a proactive compliance approach to ensure that:

  • Everyone is aware of significant issues before inspections.
  • Senior management is aware of compliance issues on site so there are no surprises during the inspection.
  • Sponsoring companies conduct due diligence before they name contractors/suppliers in applications.
  • Quality and operations work together to investigate problem and present those significant issues clearly during inspections.

Importance of Development Reports

CMOs also should have development reports that includes compiled documentation that represents a thorough understanding of the application product and process. The development report should serve as the basis of justifying the process to support the filing and should communicate product and process risks.

FDA inspections are a fact of life in commercial manufacturing of APIs and other chemical entities. Being proactive and setting up clear processes and procedures to identify any issues is key to ensuring successful outcomes.