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USP Up-to-Date initiative will impact excipient monographs. In the short term, efforts of the Excipient EC will be focused on developing specific identification tests for those excipient monographs currently lacking them. The Excipient EC will consider how to best approach analytical methods that allow better characterization of composition of excipients. FDA liaisons participate in compendial excipient monograph development to the extent possible in fulfillment of the Agency’s role in promoting development of pubic standards which in turn promote pharmaceutical quality and patient safety. The workshop identified possible opportunities for developing additional general chapters that could help drug makers gain a better understanding of excipient composition (impurities, physical/chemical properties that may impact variability) to select the right excipient.


Submitting a Request for Revision to USP


The purpose of a Request for Revision (RFR) generally is to create a new monograph for a new excipient or to revise or update an existing monograph; note that every revision must be meaningful, add value to the public standard, and contribute to the public health.13


USP is actively


engaged in updating official USP–NF monographs that currently utilize outdated technology, have safety/environmental concerns, or are missing procedures for key attributes such as identification, assay, and impurities, with a goal of improving characterization of the excipient.


An RFR for an USP–NF excipient monograph justifies the specification and typically includes the following sections (not every excipient monograph will contain every section): name (title), description (structure, molecular weight, CAS), definition, identification, assay, other components, impurities, specific tests, and additional requirements (packaging and storage, labeling, reference standards) (see Table 1). The Checklist for Submitting Requests for Revision to the USP–NF is available on the USP website.13


Conclusions


USP–NF excipient monographs need to be Up-to-Date to provide maximum benefit to the FDA, manufacturers and users of excipients. Monographs for excipients should be updated periodically to reflect current understanding regarding the role of excipients in new drug formulations and function in the manufacturing process, and because of the ever-expanding use of excipients. The control of impurities that may contribute to deteriorating product quality, the addition of a test that can reveal the composition of an excipient and the inclusion of permitted additives preventing product degradation are key examples of how the monograph can play a critical role in defining the minimum standard of excipient quality.


Monograph development can help meet increasing and newly identified challenges faced in the formulation of drugs and drug delivery systems including stabilization of the higher-order structure of active substances in biologics. Naming of excipients using the


38 | | May/June 2016


official name can be integrated into a future version of IID to eliminate confusion for IID users. General chapters on excipient composition could allow all stakeholders to more readily distinguish between impurities and concomitant components. General chapters could also help drug developers gain a better understanding of excipient composition (impurities, physical/chemical properties that may impact variability) thereby helping select the excipient best suited for the intended purpose.


References


1. FDA Guidance for Industry Q8 (R2) Pharmaceutical Development http://www.fda. gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ ucm073507.pdf


2. USP 38 – NF 33 (United States Pharmacopeial Convention) General Information Chapter, Good Manufacturing Practices for Bulk Pharmaceutical Excipients <1078>, Rockville, MD: USP; 2015.


3. FDA CDER Inactive Ingredient Database (IID) http://www.accessdata.fda.gov/scripts/cder/ iig/index.cfm accessed December 26, 2015


4.


S. Ali, Challenges and Opportunities in Development of Novel Excipients & Monographs in USP, Presentation in USP 2nd Excipients Workshop, Nov. 17-18, 2015.


5. FDA CDER/CBER Guidance for Industry Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients 2005 http://www.fda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/Guidances/ucm079250.pdf Accessed on January 20, 2016


6. K. Otilia, Application Challenges and Examples of New Excipients in Advanced Drug Delivery Systems, American Pharmaceutical Review, Mar. 01, 2011


7. USP Priority New Monograph Items http://www.usp.org/usp-nf/development-process/ priority-new-monographs Accessed December 26, 2015


8. USP List of missing excipients accessed December 26, 2015 http://www.usp.org/usp-nf/ development-process/priority-new-monographs/list/excipients


9. USP Donor recognition program Accessed December 26, 2015 http://www.usp.org/usp- nf/development-process/donor-recognition-program USP website missing monographs


10. R. Moreton, Functionality and Performance of Excipients in a Quality-by-Design World, Part IX: New Excipients. American Pharmaceutical Review Apr 34-37 (2010).


11. USP comments regarding the enhancement of the utility and usability of the Inactive Ingredient Database [Docket No. FDA–2015–N–2986] http://www.regulations.gov.


12. Stimuli to the Revision Process: USP Responses to Comments on Stimuli Article: Co- processed Excipients, PF 37(3) [May–June 2011].


13. USP Monograph Submission Guideline - Submitting Requests for Revision to the USP–NF http://www.usp.org/usp-nf/development-process/submit-new-monographs/submission- guidelines Accessed December 26, 2015


14. G. Amidon, C. Sheehan, Compendial Standards and Excipient Performance in the QbD era: USP Excipient Performance Chapter <1059>, American Pharmaceutical Review, 2011.


15. The NIPTE-FDA Excipients Knowledge Base https://pharmahub.org/ accessed on December 27, 2015.


16. USP 38 – NF 33 (United States Pharmacopeial Convention) General Notices, 4.10 Monographs. USP, Rockville, MD, USA, 2015


17. USP 38 – NF 33 (United States Pharmacopeial Convention) General Information Chapter, Excipient Performance s <1059>, Rockville, MD: USP; 2015.


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