Consistent with ICH Q3A and Q3B low reporting thresholds may be required if impurities are extremely toxic and the USP monograph is a convenient publicly available quality standard to inform all stakeholders. Industry utilizes the USP/ICH reporting thresholds as a guide to identifying the Quantitation Limit (QL) of the method. Having the FDA approved reporting threshold in the USP monograph, provides industry with an indication of the expectations of the QL that FDA would consider acceptable for the method. Without the reporting threshold in the USP monograph, industry may submit a method with a QL that does not meet FDA ’s expectations. For example, an applicant submits a method with a QL of 0.03% and FDA may request the applicant to resubmit to establish the QL at 0.01%. In this case, it will require the applicant to revalidate the method and re-assess all the impurity data provided in the submission, including stability. It may also require the applicant to expend time and resources in identifying minor peaks. All of which would increase the cost of the drug, but more importantly, potentially delay the availability of generic medicines to the patient. Therefore, reporting thresholds, provides for a uniform expectation for firms to verify that their execution of the USP or house method can achieve the necessary limit of quantitation to accurately report both individual and total impurities. AAM acknowledges that there will be instances where the public standard will need to be changed based upon new learnings or new drug products that will be introduced using the same drug substance. AAM encourages the use of the available procedures such as the pending monograph procedure so that the FDA can assure that as standards evolve and change, all stakeholders are able to participate and be included in the process. The Agency should utilize the USP, as it is a useful tool, to communicate public quality standards and expectations. Lastly, AAM would like additional clarity to the impact, if any, to the following: • For approved products where USP monographs are revised to remove the reporting threshold? • Will industry need to re-evaluate the reporting threshold in the impurity methods that were already approved by FDA based on the previous version of the USP monograph? In conclusion, AAM appreciates the opportunity to provide comments and looks forward to further dialogue with the USP on this topic. Sincerely, David R. Gaugh, R.Ph. Senior Vice President for Sciences and Regulatory Affairs
3 Current AAM Membership List Regular Members 3M Drug Delivery Systems Accord Healthcare Inc. American Regent Amneal Pharmaceuticals, LLC Apotex Corporation Argentum Pharmaceuticals Aurobindo Pharma USA Bausch Health Cipla USA, Inc.
- Spring '19
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- Pharmacology, Generic drug, Food and Drug Administration