AIP is Application Integrity Policy. The policy focuses on the integrity of data and information in applications submitted for Agency (FDA) review and approval.
The AIP described Agency's approach regarding the review of applications that may be affected by wrongful acts that raise significant questions regarding data reliability.
Although the guidance document does not create or confer any rights for or on any person and does not operate to bind FDA or the public, it does represent the Agency's current thinking on consistent implementation of the AIP.
The AIP is invoked when a company’s actions raise significant questions about the integrity of data in drug applications including falsification. Under the AIP, FDA asks the company to cooperate with the agency to resolve the questions of data integrity and reliability. This includes implementing a Corrective Action Operating Plan (CAOP) to provide assurance of the integrity.
To download policy document, click here
Has FDA invoked AIP for any Indian company?
To best of my knowledge, there is no other company from India for which AIP has been invoked, except the Japanese-Indian company - Ranbaxy Laboratories Limited.
Given below is a Case Study on AIP invoked to a company, its consequences and handling of events.
U.S. Food and Drug Administration announced that a facility owned by India-based Ranbaxy Laboratories falsified data and test results in approved and pending drug applications. The facility, Paonta Sahib, was already under an FDA Import Alert since September 2008. To address the falsified data, the FDA has invoked its Application Integrity Policy (AIP) against the Paonta Sahib facility. The AIP is invoked when a company’s actions raise significant questions about the integrity of data in drug applications. Under the AIP, the FDA has asked Ranbaxy to cooperate with the agency to resolve the questions of data integrity and reliability. This would include implementing a Corrective Action Operating Plan (CAOP) to provide assurance of the integrity.
What led FDA to invoke AIP to Ranbaxy?
In the backdrop, when two facilities of Ranbaxy Labs were audited by US FDA Inspectors in the February 2006, the inspections reveal significant deviations from cGMP. Ranbaxy issued three responses (March 20, April 20 and May 25) to these observations. However, the FDAs review of Ranbaxy response didn’t helped much and FDA said in its letter about the still valid concerns.
As these responses and the supporting documentation from Ranbaxy continued to be examined by CDER against the filed applications, it was reveled that apart from significant GMP deviations, the company falsified data and test results in approved and pending drug applications.
The AIP memorandum issued by CDER dated February 25th, 2009 says that CDER has determined that “Ranbaxy submitted untrue statements of material fact in abbreviated and new drug applications filed with the Agency. These findings concern the submission of information, such as from stability test results in support of pending and approved drug applications, from the Ranbaxy Laboratories Limited site located at Paonta Sahib”.
The AIP copy can be downloaded from here
For the benefit of readers it is worth to mention that FDA has stated in its website that
“To date, the FDA has no evidence that these drugs do not meet their quality specifications and has not identified any health risks associated with currently marketed Ranbaxy products.”