The FDA conducts Pre-Approval Inspections (PAI) to assure that a facility can manufacture the intended product and that the submitted application is complete and accurate. The PAI will evaluate a drug manufacturing facility’s production capability and establish whether the applicants’ manufacturer can adequately produce and sell the product it is applying for commercially. Manufacturers named for the first time in a new drug application (NDA), an abbreviated drug application (ANDA), a biologics license application (BLA), or a premarket approval application (PMA) are subject to PAIs.

A PAI may be performed at any facility listed in the application, such as active pharmaceutical ingredient (API) producers, control testing laboratories, and packaging facilities. During a PAI, FDA inspectors evaluate and assess the following at each site:

  • cGMP compliance
  • Conformance to application
  • Manufacturing reliability
  • Authenticity and accuracy of data
  • Ability to scale-up
  • Adequacy of analytical methods

How should a company prepare for a PAI?

Companies should consider executing a mock PAI 6-12 months before the actual PAI, allowing plenty of time to remediate any identified concerns and prepare for the formal inspection.

PAI Readiness Actions:

  • Inspection Readiness Training
    • Provide site-level guidance to any individuals who could be affected by the inspection. Focus on what to expect, how to cooperate with inspectors, and how to prepare.
  • Set up a PAI Readiness Team
    • Including people such as quality auditors and relevant management
    • Have specific people answer chemistry, microbiology, facility/processing, formulations, suppliers, and quality systems-related questions.

Before the inspection, the PAI readiness team should gather to calibrate and ensure everything is readily available for presentation. During each day of the inspection, the PAI readiness team should meet to examine observations and prepare any requests for the following day after the inspector leaves.

Results of the Pre-Approval Inspection

Following the PAI, the lead investigator will either endorse approval or withhold approval. Recommending approval implies there were no significant issues that surfaced during the inspection. Recommending withholding of approval indicates the site is not entirely cGMP compliant,  the submitted information is not accurate or complete, or in line with site records. When approval has been withheld, the company must respond to the stated observations appropriately.

Firms need to realize that the pre-approval inspection is the starting point for all future inspections. Once the application is approved, the facilities are subject to routine inspections. While the FDA uses a risk assessment to determine the regularity of inspections, domestic firms can generally expect an inspection every 2-years, and a business located outside the United States can usually expect to be notified of an approaching inspection.

If you have any additional questions about conducting a PAI or submitting an application to a notified body, experts at EMMA International can help. Contact EMMA International at 248-987-4497 or by email at info@emmainternational.com.

Alexis Ferrier

Alexis Ferrier

Alexis is a Technical Writer at EMMA International. She has research and development experience in both device and drug products. Additionally, Alexis has experience in quality assurance, quality control, regulatory requirements, and international compliance. She holds a Bachelor of Science in Chemistry from Michigan Technological University.

More Resources

The End of the COVID-19 Public Health Emergency

The End of the COVID-19 Public Health Emergency

After over 3 years, the COVID-19 Public Health Emergency (PHE) will end on May 11, 2023, the Biden Administration announced last week.1After 3.5 years of the modified policy to allow for amore efficient path for COVID-19-related medical products to get to market, this begs the question of how it will impact the MedTech world.
Process Validation

Process Validation

All right, you have just gotten all of your paperwork together, submitted the right forms to the right people, set up your factory, hired and trained your staff; now it’s time to make the medical devices. The regulatory nonsense is over and done, right?
The Role of Management in Product Quality

The Role of Management in Product Quality

Depending on the factory, some production employees may find it surprising that management has an important role to play in a quality system.  21 CFR 820.20 mandates that “Management with executive responsibility shall establish objectives for, and commitment to, quality”.[1]  The Federal Government expects that management takes an active interest in improving the output of their company, at least in the case of medical device manufacturers.

Ready to learn more about working with us?

Pin It on Pinterest

Share This