SPEAKERS:

Dr Christopher BurgessBurgess Analytical Consultancy

Dr Joachim ErmerSanofi, Germany

23 - 24 June 2016, Heidelberg, Germany

Practical Statistical Tools for Analytical Laboratories

Updated Course for R&D and QC Laboratories

Performance Evaluation and Monitoring for compliant Analytical Procedures and Processes

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wa/vers1/0411.2015 This education course is recognised for the ECA GMP Certification Programme „Certified Quality Control Manager“. Please find details at www.gmp-certification.eu

LEARNING OBJECTIVES:

� Participants should gain an understanding of – Basic statistical fundamentals – Distribution of data and its parameters – Accuracy and precision – Variability and precision levels – Reportable result – Linear and non-linear models – Performance requirements for analytical

procedures � Participants will be shown how to

– apply statistical principles scientifically and pragmatically in their day-to-day business – use statistical simulations – optimise the reportable result for minimum

variability – trend data – perform Design of Experiments (DoE) – compare data and methods – establish reliable Reporting/Quantitation Limits – apply statistical tools for analytical lifecycle

management

Objectives

Statistical calculations and tools are applied extensively in pharmaceutical analysis including:

� Method development and validation � Transfer of analytical procedures � Setting or verification of specification limits � Data evaluation, comparison and trending

The ICH Q10 Guideline “Pharmaceutical Quality System”, the FDA Guidances on Process Validation and Methods Validation require monitoring of “process performance and product quality” and “Trend analysis on method per-formance” throughout the product lifecycle. Hence the appropriate use of statistical trending and evaluation tools has become mandatory.

Consequently, a thorough understanding of statistical fundamentals is essential in order to be able to select parameters and test methods that are ‘fit for purpose’.

Do you speak statistics?In addition, such an understanding facilitates the com-munication with other technical and regulatory functions applying statistical tools in order to ensure an overall consistent approach.

Background

The course will provide the participants with recommen-dations, tools and examples to apply scientifically and pragmatically sound statistical principles to their day-to-day business as well as to meet future challenges de-scribed above.

The relevance of such statistical tools is also increasingly recognised by the Compendia, as reflected, for example, in the USP General Information Chapter <1010> “Inter-pretation and treatment of analytical data” and the re-cently introduced <1033> “Biological assay validation” together with USP Medicines Compendium, <10> “As-sessing Validation Parameters for Reference and Accept-able Procedures”.

Statistical tools are needed, for example, to evaluate:

� Distribution of data and its parameters � How to detect outliers and trends? � How to establish the total variability of the method? � How to identify method parameters that must be controlled?

� Method performance and specification limits – Which accuracy and precision is needed to achieve

an acceptable risk of OOS results? – Scientifically based justification and optimisation of

the reportable result (single or average?) – What are the requirements for impurity methods?

� Comparison of methods and data � What are the requirements for calibration models? � How to optimise the number of calibration replicates on a scientific basis?

A brief discussion of supporting software tools (e.g. Excel, Minitab, JMP) to facilitate the generation of statisti-cal information in a consistent manner will be undertak-en. One of the main features of this new course is the balance of presentations and more than five hours of practical exercise workshops which will allow partici-pants to gain ‘hands on’ practical experience in applying the statistical methods described. By means of statistical simulation tools, the participants will gain intuitive un-derstanding of the consequences of appropriate and inappropriate performance parameters, for example the relationship between precision and OOS results.

For this reason, the course is limited to 30 participants so that individual attention and support can be given. In order to fully benefit from the workshops, attendees should preferably bring a notebook with Excel® 2007 or later.

Target Audience

This best practice oriented course is designed for analyti-cal laboratory managers and their colleagues charged with the day to day management and evaluation of labo-ratory data throughout the lifecycle, i.e. in method devel-opment, validation, transfer, specification setting, batch release and stability, continuous performance verifica-tion and change control.

QA, manufacturing and regulatory affairs professionals will benefit from participation by gaining a clear under-standing of the statistical fundamentals which are impor-tant to implement scientifically sound and pragmatic tools to conform to GMP and regulatory requirements for example Product Quality Review.

Moderator

Dr Christopher Burgess, Burgess Analytical Consultancy Ltd., UK

Practical Statistical Tools for Analytical Laboratories 23 - 24 June 2016, Heidelberg, Germany

Programme

(Normal) Distribution of Data and its Parameters � Data shape and its importance � Characterisation of distributions (Location and Dispersion)

� Probability considerations; all measurements are subject to error

� Populations and samples � Confidence intervals � What is an outlier? � Error of the error

WORKSHOP I: Understanding the Variability (Statistical Simulations)

� Range of expected data � Variability of standard deviations � Number of data and reliability of calculated standard deviations

Calculation and Evaluation of Precision Levels � System precision, repeatability, intermediate precision, reproducibility

� ANOVA: Identification of relevant variance compo-nents from injection, measurement, sample prepara-tion, intermediate conditions

� Total variability: precision of the reportable result and its optimisation

� Optimisation of single-point calibration � Relationship between precision and probability of OOS results

� Practically relevant acceptance criteria for precision

WORKSHOP II: Optimisation of Variability

� Statistically based format of the reportable result (single or average)

� Number of determinations for various levels � Probability of results outside established limits

Trending of Data � Why trend? � Evaluation; do we expect a trend or not? � Statistical Process Control principles � Types of Control charts and their application � Application to stability testing

WORKSHOP III: Control Charts & Trending

� Interactive workshop based on supplied real data sets for interpretation

� Use of Minitab for control charting � Team working on evaluation and interpretation of trend data

Design of Experiments (DoE) Principles and the Investigation of Robustness

� Why do we need Design of Experiments? � Basics of DoE � What is robustness? � Worked example of DoE to the investigation of robustness

Comparison of Data & Accuracy � Significance (F- and t-test) and equivalence tests � Statistical significance and practical relevance � Differences caused by random variability: observed and true bias

� Applications in transfer and cross-validation

WORKSHOP IV: Comparison of Data (Statistical Simulations)

� Significance and equivalence tests: influence of number of data and series

� Differences between means and variability

Calibration Models, Linear and non-Linear � What is a calibration model? � What is the difference between linear and non-linear models?

� The principle of least squares and why it is important � Applying the principles to linear and non-linear models

WORKSHOP V: Linearity (Statistical Simulations)

� Regression range and evaluation of the intercept � Extrapolation effects

Performance Requirements for Impurity Procedures � Concentration dependence of precision (Horwitz relation)

� Detection and Quantitation Limits

WORKSHOP VI: Quantitation Limit

� Basics to consider for calculation from linearity � How to determine appropriately from precision

Summary Workshop & Discussion: Appropriate Choice of Tests/Calculations

� Practical objectives and data sets are provided � The participants will discuss and define appropriate tests and parameters to be calculated

� The participants are given the calculation results and are asked to make an evaluation

� The defined tests and results are discussed in the audience

Speakers

Dr Christopher BurgessBurgess Analytical Consultancy, UKHe is a Chartered Chemist and has more than 38 years experience in the pharma-ceutical industry initially with Glaxo in Quality Assurance and Analytical R&D and then 20 years in international consul-

tancy. He is a “Qualified Person” in the European Union and a member of the European QP Association advisory board. He has been appointed to the United States Phar-macopoeia’s Council of Experts 2010 to 2015 and is a vis-iting professor of the University of Strathclyde’s School of Pharmacy and Biomedical Sciences (SIPBS). In addition, he is the chairman of the ECA Analytical Quality Control Group and a member of the Executive committee of Eu-ropean Compliance Academy. He is also a member of the USP Expert Panel on Validation and Verification en-trusted to revise General Chapters <1224>, <1225> and <1226>.

Dr Joachim ErmerSanofi, Frankfurt, GermanyHead of Quality Control Services Chemis-try, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany, and Global Reference Standards Coordinator of Sanofi. He stud-ied biochemistry at University of Halle

and has more than 25 years experience in pharmaceuti-cal analytics including development products, global re-sponsibilities as Director of Analytical Processes and Technology, and Head of Quality Control. He is member of the USP Expert Panel on Validation and Verification and of the EFPIA Quality by Design working group.

Literature

Participants of this Course can pur-chase the new Edition of Dr Ermer’s book “Method Validation in Pharma-ceutical Analysis” (Wiley VCH, Wein-heim 2014, ISBN: 978-3-527-33563-3) at a 15% reduced price! You will receive the order form for this book at the course.

Social Event

On Thursday, 23 June 2016, you are cordially invited to a social event. This is an excellent oppor-tunity to share your experiences with colleagues from other com-panies in a relaxed atmosphere.

Date

Thursday, 23 June 2016, 09.00 - 18.00 h (Registration and coffee 08.30 – 09.00 h)Friday, 24 June 2016, 08.30 - 16.00 h

Venue

NH Hotel HeidelbergBergheimer Strasse 9169115 Heidelberg, GermanyPhone +49 (0) 6221 1327 0Fax +49 (0) 6221 1327 100

Fees (per delegate plus VAT)

ECA Members € 1,490APIC Members € 1,590Non-ECA Members € 1,690EU GMP Inspectorates € 845

The conference fee is payable in advance after receipt of invoice and includes conference documentation, dinner on the first day, lunch on both days and all refreshments. VAT is reclaimable.

Accommodation

CONCEPT HEIDELBERG has reserved a limited number of rooms in the conference hotel.

You will receive a room reservation form when you have registered for the event. Please use this form for your room reservation to receive the specially negotiated rate for the duration of your stay.

Reservation should be made directly with the hotel. Early reservation is recommended.

Registration

Via the attached reservation form, by e-mail or by fax message. Or you register online atwww.gmp-compliance.org.

Conference Language

The official conference language will be English.

Organisation and Contact

ECA has entrusted Concept Heidelberg with the organisation of this event.

CONCEPT HEIDELBERGP.O.Box 10 17 64 69007 Heidelberg, Germany, Phone +49 (0)6221/84 44-0Fax +49 (0)62 21/84 44 34info@concept-heidelberg.dewww.concept-heidelberg.de

For questions regarding content:Dr Günter Brendelberger (Operations Director) at ++49-62 21 / 84 44 40 or at brendelberger@concept-heidelberg.de.

For questions regarding reservation, hotel, organisation etc.:Mr Rouwen Schopka (Organisation Manager) at ++49-62 21 / 84 44 13 or per e-mail at schopka@concept-heidelberg.de.

Heidelberg – Optimal Accessibility via Frankfurt

Airport Shuttle Service PCShttp://www.pcs-hd.de/Phone: +49 (0)6221 – 16 46 64, pcs@pcs-hd.de

TLS Airport Shuttle Service Heidelbergwww.tls-heidelberg.dePhone +49 (0)6221 77 00 77, info@tls-heidelberg.de

Lufthansa Bus Airport Shuttlehttp://www.transcontinental-group.com/en/ frankfurt-airport-shuttlesTel. +49 (0)6152 – 97 69 099, info@frankfurt-airport-shuttles.de

TrainYou can get on the train directly at the airport. Trains leave up to two times per hour and it takes less than one hour to get to Heidelberg. www.bahn.de

Easy Registration

Reservation Form:CONCEPT HEIDELBERGP.O. Box 10 17 6469007 HeidelbergGermany

Reservation Form:+ 49 6221 84 44 34 @ e-mail:

info@concept-heidelberg.de Internet:www.gmp-compliance.org

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