|Celia Cruz, Ph.D., Director|
Division of Product Quality Research, Office of Testing and Research/OPQ/CDER
10903 New Hampshire Avenue
Building 64, First Floor
Silver Spring, MD 20993
As director for a research division, I support research in advance analytics for product quality and bioanalytics, manufacturing innovation, and understanding of product quality of complex dosage forms. My particular interests are focused on evaluation of emerging technologies for the modernization of pharmaceutical manufacturing and the link to product quality. Our division is equipped to handle research in all aspects of drug product quality, including formulation and analysis, to provide input to policy development and product review. The understanding of abuse deterrence formulations and related performance properties is a high priority research interest, due to its impact on public health and cross-section of analytical and manufacturing challenges.
Proposed Research Project for FDA Commissioner's Fellow
The opioids abuse epidemic continues to plague the American public and there is national budgetary, scientific and political focus on developing solutions to this crisis. According to HHS, the majority of deaths from drug overdose in 2014 (6 out of 10) involved an opioid, while the number of deaths due to overdose, continue to climb yearly . Ensuring that safe and effective abuse deterrent formulations (ADFs), both innovator and generic, are available to the American public is an important goal for CDER, in order to contribute to the potential solutions to the opioid crisis.
On October 31-Nov 1, 2016, FDA hosted a public meeting on Pre-Market Evaluation of Abuse-Deterrent Properties of Opioid Drug Products, where generic and innovator companies provided input, along with academia and FDA, on the major outstanding issues for the development and regulation of ADFs. The intent of this research plan is to generate data that will inform the next phase of policy and review of generic and new drug ADF.
1. RLD Characterization and Verification of ADF invitro Studies
- Standard evaluation of all RLDs approved as ADF, considering all potential routes of abuse. This includes the development of standard protocols and methods for manipulation and in-vitro analysis of each RLD product and route of abuse, taking into consideration the RLD design. Establish a profile for each RLD for FDA comparisons of future products, and for can be input into guidance and review.
- Comprehensive understanding of the target product profile for all approved ADF.
- Understanding the failure modes of AD properties upon storage and exposure to normal, accelerated and stressed conditions typical for the solid oral dosage forms, e.g.
- Definition of potential critical quality attributes (whether new or existing) that link to AD and are measurable during product shelf life and stability studies.
- Analysis for any correlations or links between in vitro attributes and outcomes for ADF.
3. Review of ADF properties in generic products
Understand and categorize the common development approaches and potential gaps in current ADF generic submissions. Support the ADF research and review team with incorporation of lessons learned into reviews.
- Ph.D. in Pharmaceutical Sciences or Physical Chemistry with focus on pharmaceutical materials.
- Excellent oral and written communications skills
- Desire to work in and learn about complex regulatory issues involving research, review and policy
- Willingness to travel to St. Louis OTR laboratories up to 15% of the time.
1) 21st Century Cures Act: Provide $1Billion in grants to states to address opioid crisis: https://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/documents/114/analysis/20161128%20Cures%20Fact%20Sheet.pdf
Selected Recent Publications
1. Rahman Z, Zidan A, Korang-Yeboah M, Yang Y, Siddiqui A, Shakleya D, Khan M, Cruz C, Ashraf M. Effects of excipients and curing process on the abuse deterrent properties of directly compressed tablets, Int J of Pharmaceutics, Volume 517, Issues 1–2, 30 January 2017, Pages 303–311.http://dx.doi.org/10.1016/j.ijpharm.2016.12.015
2. Lee SL, O’Connor T, Yang X, Cruz CN, Chatterjee S, Madurawe R, Moore CM, Yu L, Woodcock J. (2015)”Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production”. J Pharm Innov.10 (3):191-199, DOI: 10.1007/s12247-015-9215-8
3. Tyner K, Zou P, Yang X, Zhang H, Cruz CN, and Lee SL. (2015) “Product quality for nanomaterials: current US experience and perspective”. WIREs Nanomed Nanobiotechnol 2015. (7) 5. DOI: 10.1002/wnana.1338
4. Bartlett J, Brewster M, Brown P, Cabral-Lilly D, Cruz CN*, David R, Eickhoff WM, Haubenreisser S, Jacobs A, Malinoski F, Morefield E, Nalubola R, Prud’homme RK, Sadrieh N, Sayes CM, Shahbazian H, Subbarao N, Tamarkin L, Tyner K, Uppoor R, Whittaker-Caulk M, Zamboni W. “Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks”. AAPS J (2015) 17:44-64. DOI 10.1208/s12248-014-9701-9
5. McDermott M, Chatterjee S, Hu X, Ash-Shakoor A, Avery R, Belyaeva A, Cruz C, Hughes M, Leadbetter J, Merkle C, Moot T, Parvinian S, Patwardhan D, Saylor D, Tang N, Zhang T (2015). “Application of Quality by Design (QbD) approach to Ultrasonic Atomization Spray Coating of Drug Eluting Stents”. AAPS PHARMSCITECH, 16 (4), August 2015: 811-823. DOI 10.1208/s12249-014-0266-9