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EXCIPIENTS KNOWLEDGE MANAGEMENT: CHALLENGES & SOLUTIONSAJAZ S. HUSSAIN, PH.D., THE NATIONAL INSTITUTE OF
PHARMACEUTICAL TECHNOLOGY & EDUCATION
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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Outline
• PharmaHUB: NIPTE-FDA Excipients Knowledge BaseBackground
• Constraints on effective use and reuse of prior knowledge in regulatory decision-making Challenge
• Are we defining the problem too narrowly?Question
• An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge BaseAnswers
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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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
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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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," https://pharmahub.org/resources/458
PHARMAHUB
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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Computational environment with visualization and data mining tools
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
5
Outline
• PharmaHUB: NIPTE-FDA Excipients Knowledge BaseBackground
• Constraints on effective use and reuse of prior knowledge in regulatory decision-making Challenge
• Are we defining the problem too narrowly?Question
• An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge BaseAnswers
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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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
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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Outline
• PharmaHUB: NIPTE-FDA Excipients Knowledge BaseBackground
• Constraints on effective use and reuse of prior knowledge in regulatory decision-making Challenge
• Are we defining the problem too narrowly?Question
• An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge BaseAnswers
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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Are we defining the problem too narrowly?
Current status of ‘Substances In Regulatory
Practice’
• Global Ingredients Archive System (GInAS)
• ISO 11238 (ISO IDMP), some challenges
FDA’s Inactive
Ingredient Database -
status?
•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’
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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What about?
EMA-FDA pilot program for
parallel assessment of Quality-
by-Design applications
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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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
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
11 Paradigm shifted long-ago from ‘compounding’ to manufacturing & from testing –to-document quality to Quality by Design
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 http://www-ksl.stanford.edu/kst/what-is-an-ontology.html
Outline
• PharmaHUB: NIPTE-FDA Excipients Knowledge BaseBackground
• Constraints on effective use and reuse of prior knowledge in regulatory decision-making Challenge
• Are we defining the problem too narrowly?Question
• An opportunity to collaborate and build on the work already done - NIPTE-FDA Excipients Knowledge BaseAnswers
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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We are defining the problem too narrowly
• We have harmonized on a regulatory methodology for QbD (e.g., ICH Q8)
Our paradigm of pharmaceutical quality sifted
long-ago
• How good are the scientific explanations in regulatory submissions?
• Risk-assessment - metaphysical or an epistemological category?
However, with the prevailing ontological gaps (for example as
illustrated in the continuing challenges posed with the current FDA’s Inactive Ingredient
Database)
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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Speed to market and getting it right the first time: Improve pharmaceutical knowledge management
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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Venkat Venkatasubramanian; Rex Reklaitis; Leaelaf Hailemariam; Shuo-Huan Hsu; Pradeep Suresh (2007), "Pharmaceutical Informatics," https://pharmahub.org/resources/30
Summary
• Shifted long ago; regulatory methodology outlined for QbDParadigm
• Serious gaps; unconvincing epistemology Ontology?
• Our risk-assessment - metaphysical or an epistemological category?Risk
• Work already done on the NIPTE-FDA Excipients Knowledge BaseLeverage
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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In the context of knowledge sharing ontology is a specification of a conceptualization (enabling knowledge sharing and reuse)
NIPTE-FDA Excipients Knowledge BaseContact at NIPTE
• Stephen W. Hoag, Ph.D.
• University of Maryland, Baltimore
• School of Pharmacy
• Phone 410-706-6865
• Email: [email protected]
IFPAC® Annual Meeting, Jan. 24 - Jan. 27, 2016 . Arlington, VA, U.S.A
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