Pre-Approval Inspections (PAIs) are one of several significant milestones with an outsized impact on product approval and market entrance in FDA regulated industries.
While organizations that have successfully navigated product development before often ingrain PAI readiness into their processes, companies of all sizes routinely need to devote time and energy to diligent preparation. Very often, that means augmenting their limited internal resources by utilizing external reviewers and auditors to conduct mock audits and remediate as needed prior to the PAI.
The FDA conducts Pre approval Inspections to assure that a manufacturing site named in a drug application can manufacture the product and that the data submitted in the application is complete and accurate.
Any manufacturing site named for the first time in an NDA, ANDA, BLA, or PMA is subject to a PAI. These inspections are carried out at all kinds of facilities listed in applications, including API manufacturers, testing labs, and packagers, among others.
During a PAI, regulators will be looking to confirm the following:
1) Readiness for Commercial Manufacturing;
- The site demonstrates manufacturing reliability
- The site can scale its operations
2) Conformance to Application
- The site conforms to the application
3) Data Integrity Audit
- The site is using suitable and adequate analytical methodologies
- The site is producing authentic and accurate data
- The site is in full CGMP compliance
A Mock PAI planned and executed by a knowledgeable and experienced auditing professional is a critically important assurance activity. But a mock assessment is just one step in preparing for a PAI.
In terms of timing, companies should strongly consider holding a Mock PAI roughly one year ahead of FDA’s inspection to allow time for any necessary remediation.
Following this assessment, any findings that require attention should be remediated through a diligent remediation project.
Preparation should be a cross-functional project that incorporates training, compliance, organization, and validation.
As part of any preparation plan, companies should designate a readiness team, identify and work with subject matter experts who will be involved, and ready their facility to receive regulators.
Priority PAI criteria include:
- A facility being named for the first time in an application
- An applicant’s first application
- The first ANDA for an approved drug
- New molecular entities
- Narrow therapeutic range drugs
- High-risk APIs
- Multiple changes to a site, process, and/or product
- OAI status or no recent inspection
General PAI criteria include:
- Sites producing difficult-to-manufacture drugs
- Site compliance record considerations
- Corporate compliance record compliance
- Recent inspections
- Supply chain risk
Read also: FDA Findings and Remdies on cGMP Violations
Resource Person: BARBARA PIROLA