1 Dose Content Uniformity for Aerosol Products Wallace P. Adams, Ph.D. OPS/IO Advisory Committee for Pharmaceutical Science 13 March 2003 Rockville, MD.

Slides:

Advertisements

Similar presentations

Presented by Bo Olsson (AstraZeneca)

Advertisements

Ramana S. Uppoor, M.Pharm., Ph.D., R.Ph.

“Students” t-test.

ICH Q4B Regulatory Acceptance of Analytical Procedures and/or Acceptance Criteria (RAAPAC) Overview and Update Robert H. King, Sr. Office of Pharmaceutical.

USP and Dissolution Testing Advisory Committee for Pharmaceutical Sciences 2 May 2005 Will Brown Staff Liaison to the Biopharmaceutics Expert Committee.

Profile Analysis of Cascade Impactor Data: An Alternative View Andrew R Clark, Ph.D. Orally Inhaled and Nasal Drug Products Subcommittee of the Advisory.

Statistical Approaches to Addressing the Requirements of the New FDA Process Validation Guidance for Small Molecules 1 Jason Marlin, MS/T Statistics, Eli.

Parametric Tolerance Interval (PTI) Test for Delivered Dose Uniformity (DDU) for Orally Inhaled and Nasal Drug Products (OINDP) Michael Golden On behalf.

Best Practices for OINDP Pharmaceutical Development Programs Leachables and Extractables PQRI Leachables & Extractables Working Group PQRI Training Course.

Pharmaceutical Nomenclature Issues and challenges Moheb M. Nasr, Ph.D. Acting Director Office of New Drug Chemistry (ONDC) OPS, CDER, FDA Advisory Committee.

Pharmaceutical Product Quality Assurance Through CMC Drug Development Process Presented by Darlene Rosario (Aradigm) 21 October 2003 Meeting of the Advisory.

PK and PD Studies for Systemic Exposure of Locally Acting Drugs Industry View Lester I. Harrison, PhD Division Scientist 3m Pharmaceuticals.

FDA Nasal BA/BE Guidance Overview

Tanzania, August, 2006 Dr. Barbara Sterzik, BfArM, Bonn 1 Guidelines and Tools available TRS 937 and BTIF (Bioequivalence Trial Information Form)

Documentation of bioequivalence Drs. J. Welink Workshop on WHO prequalification requirements for reproductive health medicines, Jakarta, October 2009.

Achieving and Demonstrating “Quality-by-Design” with Respect to Drug Release/dissolution Performance for Conventional or Immediate Release Solid Oral Dosage.

1 Process to Address Specifications for Delivered Dose Uniformity of Inhaled and Nasal Drug Products Presented by Robert O’Neill, Ph.D. Chair ACPS Working.

Statistical Considerations in Setting Product Specifications

ITFG/IPAC Collaboration CMC Specifications Technical Team ITFG/IPAC TECHNICAL TEAM: CMC SPECIFICATIONS Presented by: Bo Olsson, PhD 26 April 2000 Rockville,

Establishing Drug release/Dissolution Specifications – QBD Approach Moheb M. Nasr, Ph.D. Office of New Drug Quality Assessment (ONDQA), OPS, CDER Advisory.

Ajaz S. Hussain, Ph.D. Deputy Director Office of Pharmaceutical Science, CDER, FDA ACPS Subcommittee on Manufacturing Science: Identification and Prioritization.

1 Math 10 Part 5 Slides Confidence Intervals © Maurice Geraghty, 2009.

Ajaz S. Hussain, Ph.D. Office of Pharmaceutical Sciences CDER, FDA October 21, 2003 Welcome and Introduction to the Meeting.

1 The June 1999 Draft BA/BE Guidance for Nasal Aerosols and Nasal Sprays: History, Recommendations and Local Delivery Issues Wallace P. Adams, Ph.D. OPS/CDER/FDA.

Application of Monte Carlo Methods for Process Modeling

2015 MBSW1 Quality Assurance Test of Delivered Dose Uniformity of Multi-dose Spray and Inhalation Drug Products Drs. Yi Tsong 1, Xiaoyu (Cassie) Dong*

1 Bioequivalence of Highly Variable Drugs: Regulatory Perspectives Sam H. Haidar, R.Ph., Ph.D. Pharmacometrics Office of Generic Drugs.

John R. MurphyACPS 10/ Zero Tolerance Criteria Do Not Assure Product Quality John R. Murphy, Ph.D. Meeting of the Advisory Committee for Pharmaceutical.

University of Ottawa - Bio 4118 – Applied Biostatistics © Antoine Morin and Scott Findlay 08/10/ :23 PM 1 Some basic statistical concepts, statistics.

Chapter 13 – Difference Between Two Parameters Math 22 Introductory Statistics.

1 PAT and Biological Products Tom Layloff FDA-SGE Management Sciences for Health The views expressed here are those of the author and not necessarily.

ACPS Meeting, October 19-20, 2004 BioINequivalence: Concept and Definition Lawrence X. Yu, Ph. D. Director for Science Office of Generic Drugs, OPS, CDER,

1 Advisory Committee for Pharmaceutical Science and Clinical Pharmacology July , 2008 Classification of Orally Disintegrating Tablets Frank O. Holcombe,

Introduction to Topic #1: QbD approach for quality control and assurance of Dissolution Rate Ajaz S. Hussain, Ph.D. Deputy Director, Office of Pharmaceutical.

Parametric Tolerance Interval Test for Delivered Dose Uniformity (DDU) Working Group Update Moheb M. Nasr, Ph.D. Office of New Quality Assessment (ONDQA,

Bioequivalence Studies and Other Recommendations for Orally Inhaled and Nasal Drug Products: Work of the ITFG/IPAC-RS Collaboration Presented by Cynthia.

A Process Control Screen for Multiple Stream Processes An Operator Friendly Approach Richard E. Clark Process & Product Analysis.

Waiver of In Vivo Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Ajaz S. Hussain,

1 ORALLY INHALED AND NASAL DRUG PRODUCTS FOR LOCAL ACTION Current FDA BA/BE Background and Issues Wallace P. Adams, Ph.D. OPS/CDER/FDA OINDP Subcommittee.

1 Basis of the Proposed Tactical Plan for a QbD approach for Quality Control and Assurance of Dissolution Rate Ajaz S. Hussain, Ph.D. Deputy Director,

The USP Performance Test Dissolution Systems Suitability Studies Walter W. Hauck, Ph.D. USP Consultant Presentation to Advisory Committee for Pharmaceutical.

Meiyu Shen, PhD Collaborators: Xiaoyu Dong, Ph.D., Yi Tsong, PhD

COMPARABILITY PROTOCOLUPDATE ADVISORY COMMITTEE FOR PHARMACEUTICAL SCIENCE Manufacturing Subcommittee July 20-21, 2004 Stephen Moore, Ph.D. Chemistry Team.

Statistical Quality Control

Guidance Update: Average, Population, and Individual Approaches to Establishing Bioequivalence Mei-Ling Chen, Ph.D. Associate Director Office of Pharmaceutical.

Inhalation Devices Heba Abd El-fattah Sabry Pharm D.

1 METHODS FOR DETERMINING SIMILARITY OF EXPOSURE-RESPONSE BETWEEN PEDIATRIC AND ADULT POPULATIONS Stella G. Machado, Ph.D. Quantitative Methods and Research.

Blend Uniformity: Update Ajaz S. Hussain, Ph.D.. Background Issue: Assuring and documenting “adequacy of mixing” operations –PQRI’s Proposal Stratified.

Summarizing Risk Analysis Results To quantify the risk of an output variable, 3 properties must be estimated: A measure of central tendency (e.g. µ ) A.

1 Subcommittee Report: Orally Inhaled and Nasal Drug Products (OINDP) Wallace P. Adams, Ph.D. OPS/CDER/FDA Advisory Committee for Pharmaceutical Science.

1 PTIT for DCU of OINDP: Approaches to Resolution of Identified Issues Wallace P. Adams, Ph.D. OPS/IO Advisory Committee for Pharmaceutical Science 21.

1 PAT Subcommittee Closing Report 12 March 2003 Tom Layloff Acting Chair.

ITFG/IPAC Collaboration Introduction OVERVIEW OF ITFG/IPAC COLLABORATION Presented by: Harris Cummings, PhD 26 April 2000 Rockville, MD.

ITFG/IPAC Collaboration BA/BE Technical Team ITFG/IPAC TECHNICAL TEAM: BA/BE IN VITRO AND IN VIVO TESTS Presented by: Stephen Farr, PhD 26 April 2000 Rockville,

Bioequivalence Criteria Research Plan Stella G. Machado, Ph.D. Office of Biostatistics and the Replicate Design Technical Committee Advisory Committee.

Lawrence X. Yu, Ph.D. Director for Science Office of Generic Drugs, OPS, CDER, FDA ACPS Meeting, ACPS Meeting, Oct. 22, 2003 Office of Generic Drugs Research.

Orally Inhaled and Nasal Drug Products Subcommittee Introduction and Objectives Eric B. Sheinin Deputy Director Office of Pharmaceutical Science Center.

Evaluation of a Scaling Approach for Highly Variable Drugs Sam H. Haidar, Ph.D., R.Ph. Office of Generic Drugs Advisory Committee for Pharmaceutical Sciences.

FLEMINGTON PHARMACEUTICAL CORPORATION Develops therapeutic entities in Lingual Spray Delivery Systems!

Orally Inhaled and Nasal Drug Products (OINDP) Subcommittee Report to the Advisory Committee for Pharmaceutical Sciences Rockville, Maryland November 15,

3M Drug Delivery Systems 3 Introduction The headspace of pressurized metered dose inhaler (MDI) canisters is filled by the vapor of volatile components,

3M Drug Delivery Systems 3 Introduction A combination MDI product has been developed containing two active drug substances (designated as A and B) in solution,

Ajaz S. Hussain, Ph.D. Office of Pharmaceutical Sciences CDER, FDA October 21, 2003 Dose Content Uniformity: Parametric Tolerance Interval Approach.

Office of Pharmaceutical Science OPS Center for Drug Evaluation and Research CDER FDA Food and Drug Administration HHS Health and Human Services 1 Advisory.

Parametric Tolerance Interval (PTI) Test for Delivered Dose Uniformity (DDU) for Orally Inhaled and Nasal Drug Products (OINDP) Michael Golden On behalf.

An Assessment of IPAC-RS’ Proposal Walter W. Hauck, Ph.D. Biostatistics Section Division of Clinical Pharmacology Thomas Jefferson University Philadelphia,

Ondrej Ploc Part 2 The main methods of mathematical statistics, Probability distribution.

WHO Technical Report Series, No. 953, 2009

USP and Dissolution Testing

USP and Dissolution Testing

Presentation transcript:

1 Dose Content Uniformity for Aerosol Products Wallace P. Adams, Ph.D. OPS/IO Advisory Committee for Pharmaceutical Science 13 March 2003 Rockville, MD

2 Two Guidances Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products - CMC Documentation (Draft, October 1998) Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products - CMC Documentation (Final, July 2002)

3 The DCU and SCU Issue DCU (dose content uniformity) SCU (spray content uniformity) Uniformity of metered doses from an MDI, DPI or nasal spray –within a container for multiple dose products –among containers –among batches

4 Present DCU and SCU Tests Nonparametric (with a parametric element) Single dose and multi-dose products At tier 1 –NMT 1 of 10 containers outside of % of label claim (LC) –0 outside % of LC –Mean of 10 not outside % LC

5 Present DCU and SCU Tests: DCU Through Container Life for Multi-dose Products MDIs –DCU measured at B, M and E lifestages –for each of three containers –NMT 1 of 9 determinations outside % of LC –0 outside % of LC –means at each of B, M and E not outside % of LC

6 Present DCU and SCU Tests: DCU Through Container Life for Multi-dose Products DPIs (device-metered) –Same as for MDIs Nasal sprays –Similar to MDIs, except 10 determinations at B and 10 at E

7 A Parametric Tolerance Interval Approach General form of the criterion: Y  kS where: Y = absolute value (LC - sample mean) k = a tolerance interval constant s = sample std dev Per discussion with Dr. Walter Hauck

8 A Parametric Tolerance Interval Intended to control ranges of specified coverage, e.g., –85% of the doses within – % of LC at –95% confidence We therefore specify –min proportion of the batch that should fall within the limits (coverage) –acceptable tolerance limits (target interval) –degree of confidence Per discussion with Dr. Walter Hauck

9 Development Of Parametric Tolerance Interval Approaches Official in Japanese Pharmacopoeia (JP, 1996) Pharmacopoeial Discussion Group –European Pharmacopoeia, JP, and USP Statistics Working Group of PhRMA ICH/PDG Task Force

10 Development Of Parametric Tolerance Interval Approaches, cont. Content Uniformity and Dose Uniformity: Current Approaches, Statistical Analyses, and Presentation of an Alternative Approach, with Special Reference to Oral Inhalation and Nasal Drug Products –RL Williams et al, Pharm Res, 2002;19: A Parametric Tolerance Interval Test for Improved Control of Delivered Dose Uniformity of Orally Inhaled and Nasal Drug Products –IPAC-RS, 15 November 2001

11 OPS Issues Definition of limiting quality –Essential to an acceptable DDU test 85% of doses in the batch within % of label claim? 85% of doses within % of label claim? 90% of doses within % of label claim? 90% of doses within % of label claim? other options?

12 OPS Issues Robustness of the test –for non-normally distributed data e.g., short-tailed distribution –properties of the test when the batch is at or below the IPAC-proposed limiting quality (e.g., 85% coverage)

13 OPS Issues Impact of eliminating the zero tolerance criterion (ZTC) –IPAC-RS claims that ZTC increases producer risk with little improvement in consumer protection –value for skewed data

14 OPS Issues  level (less than or equal to 0.05) –Estimated consumer risk of IPAC-RS proposal exceeds 5% –Approaches to assuring   0.05

15 Question # 1 for ACPS Does ACPS agree that a parametric tolerance interval test is conceptually acceptable as a replacement for the agency’s nonparametric (with certain parametric elements) DCU and DCU through container life tests for OINDPs?

16 Question # 2 for ACPS Does ACPS feel that DCU quality standards should provide assurance that batch failure rates do not exceed some specified level, e.g., 10%?

17 Acknowledgments Ajaz Hussain (FDA) Guirag Poochikian (FDA) Don Schuirmann (FDA Meiyu Shen (FDA) Yi Tsong (FDA) Walter Hauck (Thomas Jefferson University) Roger Williams (USP)