The essentials for conducting an investigation of an out-of specification result in a compliant, reliable, and timely manner include having a well-organized and understood process; having well-informed and well-trained analysts, supervisors, and manufacturing personnel; and maintaining clear and concise documentation. The firm’s procedure for investigating out-of specification results should describe the various phases of the investigation and the recommended timing for the completion of the phases. The types of errors that may arise and how to deal with them should be defined. Checklists may help determine the presence or absence of certain types of errors. The procedure also should provide for the thorough documentation of the investigation.

The best practice is to minimize the generation of out-of specification results. Careful description of methods and reportable values, including appropriate system suitability parameters, can help to avoid out-of-specification results. Qualification of equipment and analysts and rigorous transfer of analytical technology will help to ensure that a laboratory is fully capable of performing an analytical method.

This two-day presentation will review the various items that should be included in the investigation to determine the cause of the limit excursion for both viable and non-viable excursions. It will also offer guidance on how to establish or reestablish limits that are appropriate to the specific manufacturing process. There will also be discussion on how to document the results of the investigation.

Ms. Susan R. Thompson Quality Control Manager
Gorbec Pharmaceutical Services Inc.

Susan R. Thompson has over 20 years of industry experience. Currently, she is the Quality Control Manager at Gorbec Pharmaceutical Services, Inc., a start-up formulation, scale-up, and manufacturing company. In addition to routine quality control and stability functions, her responsibilities include assisting with the design, development, and implementation of the overall quality systems. In addition, she is currently serving on a USP ad hoc Advisory Panel to the USP Packaging and Storage Expert Committee. Prior to coming to Gorbec, she was a Lead Scientist at Catalent Pharma Solutions where she managed the on-going analyst training program and directed OOS/OOT investigations for the quality control and compendial analysis group.

---

I. Regulatory Requirements

• United States vs. Barr laboratories
• US Food and Drug Administration
• Code of federal regulations
• Guidance documents
• International conference on harmonization

II. Out of Specification (OOS) Results

• Sources of OOS
• Investigating OOS results: role of quality control, quality assurance and regulatory affairs
• Notifications: internal and external

Interactive Exercise:

Developing a flowchart for OOS Investigations and retesting

III. Out of Trend (OOT) Results

• Sources of OOT
• Investigating OOT results: role of quality control, quality assurance and regulatory affairs
• Notifications

Interactive Exercise:

Identifying and managing OOT Results and conducting outlier testing.

IV. Records Management

• Deviations
• Investigations
• FDA expectations

V. Additional Topics

• Flow chart for OOS/OOT investigations
• Rationale for retest procedure in the stability program
• SOP template for OOS/OOT investigations and outlier testing

Interactive Exercise:

Review of FDA Form 483 Observations.

• Reporting of OOS results in quality and product review
• Documentation and raw data handling in case of abandoned tests, apparent errors or assignable causes
• Link of OOS investigations with deviation and CAPA system
  • Use of control charts
  • Trend analysis
• Retesting protocol and documentation
• Presenting OOS results in FDA inspections

I. Identification of OOS/OOT and Aberrant Results

• Defining of OOS,OOT and aberrant results
• SOP requirements
• Roles and responsibilities

II. Initial Assessment

• Confirming accuracy and identifying known errors
• Evaluating sources of error
• Assessing trends
• Documentation of initial assessment

III. Flow of the Investigation

• Moving beyond the initial assessment
• Planning and documentation prior to investigations
• Evaluation of investigation results
• Documentation requirements
• Expansion of investigations
• Next steps

IV. Concluding the Investigation

• What to say or not to say
• Special cases
• Closing the investigation

V. Root Causes and CAPA’s

• Going beneath the surface to identify root causes
• Writing appropriate and measurable CAPA’s
• Avoiding common problems
• Documentation and follow-up

Interactive Exercise:

Participants will discuss investigation strategies and documentation for case studies in small groups.

I. Inherent Measurement Errors

• Defining measurement errors
• Minimizing measurement errors
• Determining best practices

II. Systemic Approaches to Minimizing Errors

• Identifying sources of systematic errors
• Design and presentation of methods
• Capturing “best practices”
• Verification procedures: timeliness versus streamlining

III. Prevention and Control

• Minimizing factors that lead to analytical errors
• Redefining “training”
• Containing and controlling problems
• Practical tips

Interactive Exercise:

Participants will work in small groups to evaluate and propose minimization plans for several case studies. Each small group will present their minimization plans to the full group for discussion.

I. Identification of OOS Results

• Defining OOS requirements for differing
• Situations: raw material release, in process,
• Batch release, stability studies
• Evaluation of potential OOS results
• Regulatory obligations
• Timeliness of OOS evaluations

II. Initiation and Documentation of Laboratory Investigations

• SOP requirements
• Analyst and supervisor responsibilities
• Initial assessments
• Identification of known laboratory errors
• Documentation requirements

III. Finding the Root Cause

• Evaluation of lab-related functions
• Assessing sources of errors
• Trending data and errors
• Going beneath the surface to find the best answer - not just the easiest answer

IV. Resolution of Investigations

• Planning for investigational testing
• Documenting prior to investigational testing
• Invalidating test results
• Confirming failure

V. CAPA for Lab-Related Errors

• Determining when a CAPA is necessary
• Integration of RCA
• Writing CAPA’s that are both appropriate and measurable
• Avoiding common pitfalls

Interactive Exercise:

Example laboratory investigations will be presented at various stages in the investigation for evaluation. Participants will then work in groups to prepare conclusions and CAPA’s based on a case study. Each group will present their case study to the full workshop for discussion.

I. Differentiate OOS, an OOT and an Atypical Results

• Differences of OOS,OOT and atypical results
• Trends in results
• The importance of monitoring tools for future event avoidance

II. OOS Investigations Criticality and OOT and Atypical Results Investigations Importance

• Criticality of OOS
• Atypical results investigations
• The importance of trending for future reference; Preventing reoccurrences

Interactive Exercise:

Participants will analyze several situations and determine if there are OOS/OOT or atypical results. Attendees will receive prepared templates and examples that can be used for easy implementation.

Interactive Workshop:

Examples of OOS results in the analytical laboratory will be presented and discussed. Participations have to also identify the OOS issues and to discuss and propose specific plans of action.

Interactive Workshop:

Laboratory OOS results scenarios will be presented and evaluated in workshop groups. Attendees are then required to develop a flow chart that takes into consideration the various requirements of the guidance and describes responsibilities and the sequence of activities following an initial OOS result. Critical points will be discussed and specific issues will be addressed.

This two day workshop program is directed toward Directors, Managers, Supervisors, Analysts, and Associates in the Pharmaceutical, Biopharmaceutical, Biotechnology, and allied industries with daily responsibilities in the following areas:

• Quality Control
• Quality Assurance
• Analytical Laboratory
• Stability
• R&D
• Data Review
• Documentation and Technical Writing
• CAPA
• Product Submission
• Validation
• Product Development
• Manufacturing
• Project Management
• Training
• Contract Laboratories
• Change Control
• Qualified Persons
• Production
• Regulatory Compliance Managers
• Process Validation Engineers
• Engineering Managers
• Chemical Engineers
• Process Development
• Warehousing
• Logistics

Hilton Garden Inn Montreal Airport 7880 Cote-De-Liesse Montreal, Quebec, Canada H4T 1E7 Tel: +1-514-788-5120 Fax: +1-514-788-5025
A special room rate has been prearranged for conference participants. Call the hotel directly at the above number and mention IPA to receive the reduced room rate.  For more information, please call us at 416-410-7402 or enquiry@ipacanada.com