Residual solvents guidelines cause ANDA “uncertainty”
New regulations from the US Pharmacopeia (USP) covering the presence of residual solvents in all drug substances, excipients and products came into force on July 1 after being postponed several times.
Despite these delays, and documentation from the OGD covering how the regulations would affect abbreviated new drug applications (ANDAs), companies are still uncertain what information they have to supply.
The documentation states: “After the revised USP Chapter 467 Residual Solvents became official July 1, 2008, attempts at implementation of 467 have resulted in variability in the information being submitted to applications, and to uncertainty regarding what information would be considered satisfactory for demonstrating compliance with that chapter.”
Chapter 467 was adopted to ensure that acceptable levels of residual solvents are present in drugs in order to prevent harm to the patient. The chapter was derived from the International Conference on Harmonization (ICH) Q3C quality guidance.
Adapting to these new regulations has not gone smoothly according to the OGD and consequently it has decided to clarify what additional information manufacturers need to supply in their ANDAs.
For a submission to be considered complete it must list information on all the solvents used in the manufacture of each ingredient used in the formulation.
This includes the applicant’s test data, a demonstration that the ingredients are compliant with Chapter 467 and verification data for the USP method used.
Ingredients and products not covered by a USP monograph must also be included in a company’s ANDA.
It is hoped that by clarifying these areas and others the need for companies to file additional submissions will be minimised.
The OGD’s original documentation can be found here, with the recent additional information available here.
Draft guidance from the Center for Drug Evaluation and Research (CDER) is available here. The CDER is seeking comments and suggestions from the industry before it finalises the document.
