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:
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.
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:
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.
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.
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.