You can download the programme brochure as PDF file
Programme
OOS: US / FDA Expectations
Background to the FDA Final Guidance 2006
Long standing FDA Principles
Key points from the Final Guidance
- Scope
- Investigation Processes
- Roles and Responsibilities
- Analysis and reporting of results
- Outlier testing
- Cautions
Dr Christopher Burgess, Chairman of the ECA Analytical Quality Control Group, UK
OOS Results – European Requirements and Expectations of a European GMP Inspector
The OOS SOP
Definition of in-spec and out-spec-Results
OOS Investigation phases
Batch disposition
Surveillance of the release decision
Comparison ECA OOS SOP and MHRA approach
Dr Matthias Heuermann, European GMP Inspector, NRW Centre for Health (LZG.NRW), Germany
Fundamentals of Analytical Variability
Sources and types of variables
Measures of variables
Process Capability
Replications and reportable values
Dr Christopher Burgess, Chairman of the ECA Analytical Quality Control Group, UK
Part II - LABORATORY DATA MANAGEMENT; OOE, OOT, and OOS Results
ECA Analytical Quality Control Working Group SOP
Background
Scope and limitations
Process
Key elements and process flow
Dr Christopher Burgess, Chairman of the ECA Analytical Quality Control Group, UK
Part III - CRITICAL ASPECTS OF OOS INVESTIGATIONS
Terms Used in Out of Specification Investigations
FDA Guidance for Industry terms - many terms for the same subject, e.g. for sample – sample, lot, resample, new sample, homogenous sample, portion of a batch, etc.
Further relevant ASTM terms
GSK’s attempts to weld the FDA and ASTM terms together
How these terms direct an OOS/atypical result investigation at GSK
Dr Tony Bennett, GSK, UK
Identification, Isolation and Evaluation of Outliers: Which is the Right Number of Retests?
Consequences of inconclusive lnvestigations
Isolation approaches; How to show that the OOS result is highly unlikely to be representative of the sample population
- z scores
- Rosner's test
- Dixon's tests (and why not to use them!)
- Hampel's rule
How many retests do I need to achieve 'isolation?
Calculation approaches that take into account the outlier
- 95% confidence interval comparison with specification (Current SOP approach)
- Robust procedure H15 proposal for v2 of the SOP
Dr Christopher Burgess,Chairman of the Analytical QC Groupy, UK and Trevor Duguid Farrant
Reading Scientific Services Ltd., UK
Out-of-Trend Results
Roche’s current perspective on detecting out of trend results
Investigation of out of trend results
Dr Peter Rauenbuehler, Roche, USA
Alternative Approaches
Members of ECA’s OOS Review Team who helped to develop the ECA OOS SOP will present their comments and alternative approaches
(15 min each):
Margarida Mesquita Carvalho, Bluepharma Industria Farmaceutica S.A., Portugal
Dr Dawn Toronto, CMC & Analytical Consultant, Germany
Dr Tony Bennett, GSK, Global Manufacturing Supply, UK
Dr Peter Rauenbuehler, Roche, USA
Dr Elin Jensen, Novo Nordisk, Denmark
These ECA OOS Review Team Members will discuss their company’s actual and/or established OOS processes with focusing on differences to the ECA draft SOP with emphasis on these individual options, including e.g.
- When to start an OOS investigation
- QA involvement already in early stages?
- Scope and limitations of Phase II investigation
- Retesting - assessment and acceptance criteria
- Reporting
These inputs could form the basis for a revised and updated version 2 of ECA’s OOS SOP.
Part IV - APPLICATION-SPECIFIC CONSIDERATIONS
Pharmacopoeial Compliance
Mandatory requirements for monograph compliance
OOS and monograph compliance
Identification tests and monograph compliance
Impurity tests and monograph compliance
Compliance with specifications given in the assay - possible approaches
Dr Ulrich Rose, EDQM
OOS Results in R&D Laboratories
Drug development &analytical life cycle
Aberrant analytical data in R&D
OOE results in preclinical development & investigation medicinal products
OOE in bioassay samples
OOE and OOT results in stability studies
Dr Bernd Renger, European QP Association, Germany
OOS in Biologics
Biological Assays
Intermediates
Real time equipment or system adjustments
OOE
Stability OOS
Dr Olaf Kunze, CSL Behring, Germany
OOS in Microbiology
Di Morris, MHRA, UK