Ensuring Smooth Sailing When It Comes to FDA Inspections


As the age-old quote goes, “there’s nothing as inevitable as death and taxes,” but for API manufacturers, there’s clearly a third item, and that’s the FDA inspection.

FDA Inspections are performed to ensure companies comply with current Good Manufacturing Practices (cGMP), as well as to ensure that products that enter the market from a particular plant meets safety and quality requirements.

There are basically four different types of FDA inspections:

  1. Pre-Approval of a drug or medical device to make sure that the CMO is capable of manufacturing the drug and that submitted data is accurate and complete
  2. Post-Approval – to monitor for changes in the production and control practices after drug approval
  3. Surveillance Inspections – which cover U.S. and international manufacturers and ensure consistent quality to meet cGMP standards
  4. For Cause Inspection or Directed Inspections, which arise as a result of questionable practices or that come about due to a specific problem that has come to the FDA’s attention

Whether conducted on a routine basis, or as the final assessment prior to drug approval,

The FDA inspection is a major priority of Quality Assurance (QA) professionals at Contract Manufacturing Organizations (CMOs) everywhere.

What to Expect in an FDA Inspection

While there are elements of the FDA inspection that can be unexpected, there are general processes and steps that are standard practice with all FDA inspections.

It all begins with the application submitted to, and evaluated by, the FDA.  An organization that wants to commercialize a drug product submits an application and the FDA evaluates it and schedules an inspection, with no advance warning to the CMO (unless it’s located outside of the country). In addition to inspecting the manufacturing plant, the FDA also can inspect any outside testing facility associated with the drug or drug substance, as well as packaging and labeling operations.

Key areas of focus for the FDA inspectors, who generally are investigators, chemistry experts, microbiology experts, facility experts and formulation experts, include six core systems:

  • Quality
  • Facilities and Equipment
  • Materials
  • Production
  • Packaging & Labeling
  • Laboratory Controls

The FDA investigators look into each area to verify that a manufacturer is operating in a sufficient state of control by reference to the GMP regulations and policies. When the inspection happens, the investigators will give you a Form 482 (notice of inspection), then, during the course of the inspection, if there are any significant issues or non-compliances observed, they will be documented on Form 483. This form will identify the issue that the CMO needs to address and gives it an opportunity to appeal it.

Today, while FDA inspections are more rigorous, and can take up to a few weeks, as opposed to 2-4 days, the FDA takes a more risk-based approach and often will not require frequent inspections prior to approvals, if there is a good history of passed inspections. This was the case for PCI Synthesis in 2017 when manufacturing operations were successfully inspected prior to commercialization of a client’s two products.

How you Can Get Prepared

Prior to an FDA inspection, companies’ QA teams can take measures to make sure they are prepared.  This involves a long-term and sustained commitment to devoting the resources necessary for success. Those resources should be deployed in three essential activities: internal auditing, training, and data analysis.

  1. Internal auditing is a thorough self-assessment, including routine facility and personnel behavioral audits, in-depth critical system reviews (preventative maintenance, customer complaints, deviation investigations, etc.), and comprehensive process surveys. Internal audits can identify areas for improvement that can proactively be addressed to 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.
  2. Regular personnel training is essential to empower your employees to increase their knowledge and awareness of the activities they regularly perform. To ensure a thorough training plan, a routine gap assessment measures 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.
  3. Regular analysis and trending of data from quality systems is critical to finding and correcting hidden or subtle systemic weakness. For this to be effective, a CMO 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, they can build genuine confidence that its quality system are well prepared for an FDA inspection.

Additionally, it may sound basic, but when FDA investigators come to the door, it’s critical that your receptionist or employee answering the door is well-versed in the necessary protocols and practices.  They should receive proper identification and follow standard operating procedures for visitors entering the plant.  Then, the investigators must produce their credentials and show them to the senior official within the company.

Since many of types of documentation may be required to be produced, three things should be easily made available, including documented customer complaints, training records and preventative maintenance programs.

CMOs should not wait until an FDA inspection to make sure it is enforcing proper execution of standard operating procedures and quality control measures.  By following strict standards across all areas of operations, all the time, FDA inspections can move away from being reactive fire drills to efficient examinations of quality operations.

For more information on FDA inspections and quality control, check out: API Quality Risk Management; or Why the FDA and EMA Want You to Implement QbD.