EXCIPIENTS KNOWLEDGE MANAGEMENT: CHALLENGES & SOLUTIONS

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1 IFPAC Annual Meeting, Jan Jan. 27, Arlington, VA, U.S.A 1 EXCIPIENTS KNOWLEDGE MANAGEMENT: CHALLENGES & SOLUTIONS AJAZ S. HUSSAIN, PH.D., THE NATIONAL INSTITUTE OF PHARMACEUTICAL TECHNOLOGY & EDUCATION

2 2 Outline Background Challenge Question Answers PharmaHUB: NIPTE-FDA Excipients Knowledge Base Constraints on effective use and reuse of prior knowledge in regulatory decision-making Are we defining the problem too narrowly? An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge Base

3 3 NIPTE-FDA Excipients Knowledge Base An online resource that offers a searchable repository for excipient property measurement data Funded FDA U01 grant; NSF funding used to set up PharmaHub database infrastructure Neutral forum to bring excipient suppliers and users together to share knowledge to improve excipient usage and performance Prabir K Basu; Mansoor A Khan; Steve Hoag; Carl Wassgren; Ann Christine Catlin; Sudheera R. Fernando; Sumudinie Fernando; Kristine Margaret Alston; Ting Wang; Linas Mockus (2011), "NIPTE-FDA Excipients Knowledge Base,"

4 4 PHARMAHUB

5 5 Computational environment with visualization and data mining tools

6 6 Outline Background Challenge Question Answers PharmaHUB: NIPTE-FDA Excipients Knowledge Base Constraints on effective use and reuse of prior knowledge in regulatory decision-making Are we defining the problem too narrowly? An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge Base

7 7 Constraints on effective use and reuse of prior knowledge in the regulatory context Challenges illustrated in the gaps and issues with the Inactive Ingredient Database Excipient functionality and process capability can no longer be ignored for many complex drug delivery systems Constraints in ability to account for excipient variability in the context of impact on CQA s, risk assessment and Black Swan (per Brian Carlin) CGMP deviations, investigations and effectives of CAPA

8 8 Outline Background Challenge Question Answers PharmaHUB: NIPTE-FDA Excipients Knowledge Base Constraints on effective use and reuse of prior knowledge in regulatory decision-making Are we defining the problem too narrowly? An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge Base

9 9 Are we defining the problem too narrowly? Current status of Substances In Regulatory Practice FDA s Inactive Ingredient Database - status? Global Ingredients Archive System (GInAS) ISO (ISO IDMP), some challenges Substance Registration System (SRS) Generic listing vs. Specific Grade listing max. precedent levels Listing of Mixtures? The UNII code confusing, the National Library of Medicine yet to finalize standards for assigning UNII codes for polymers Individual Grades vs. Family Data Legal status of the IID, and FDA communications of changes to the IID DMF Implications, impact on ANDAs Delays & Refuse to File Letters

10 10 What about? EMA-FDA pilot program for parallel assessment of Qualityby-Design applications

11 11 Paradigm shifted long-ago from compounding to manufacturing & from testing to-document quality to Quality by Design ICH Q8 outlined a Methodology for QbD; however Some methods we use (e.g., excipient COA/USP) may no longer be adequate Our epistemology (explanations how do you know what you know) is too often unconvincing We have significant ontological gaps and we risk black swans In the context of knowledge sharing ontology is a specification of a conceptualization (enabling knowledge sharing and reuse); in philosophy it refers to the subject of existence

12 12 Outline Background Challenge Question Answers PharmaHUB: NIPTE-FDA Excipients Knowledge Base Constraints on effective use and reuse of prior knowledge in regulatory decision-making Are we defining the problem too narrowly? An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge Base

13 13 We are defining the problem too narrowly Our paradigm of pharmaceutical quality sifted long-ago We have harmonized on a regulatory methodology for QbD (e.g., ICH Q8) However, with the prevailing ontological gaps (for example as illustrated in the continuing challenges posed with the current FDA s Inactive Ingredient Database) How good are the scientific explanations in regulatory submissions? Risk-assessment - metaphysical or an epistemological category?

14 14 Speed to market and getting it right the first time: Improve pharmaceutical knowledge management Venkat Venkatasubramanian; Rex Reklaitis; Leaelaf Hailemariam; Shuo-Huan Hsu; Pradeep Suresh (2007), "Pharmaceutical Informatics,"

15 15 Summary Paradigm Ontology? Risk Leverage Shifted long ago; regulatory methodology outlined for QbD Serious gaps; unconvincing epistemology Our risk-assessment - metaphysical or an epistemological category? Work already done on the NIPTE-FDA Excipients Knowledge Base In the context of knowledge sharing ontology is a specification of a conceptualization (enabling knowledge sharing and reuse)

16 16 NIPTE-FDA Excipients Knowledge Base Contact at NIPTE Stephen W. Hoag, Ph.D. University of Maryland, Baltimore School of Pharmacy Phone