The 2023 PSDG Meeting was conducted within the KENX Laboratory University Event in San Diego, May 9-11, bringing together dozens of Stabilitarians, Analysts and Quality personnel to explore the latest challenges in the Stability Arena. This month’s StabilityHub Newsletter focuses on these topic areas with a brief summary of each and an invitation to all of our readers to further the discussion, raise questions of their own and share some of the approaches they have successfully used to overcome their toughest hurdles. Most of all, challenge your group to evaluate where it stands in regard to these subjects. 17 of the topic areas are discussed below; a further 17 will be the focus of the August Newsletter.

Conducting a Gap Analysis for the QC Laboratory

Kim Huynh-Ba Executive Director, PHARMALYTIK

Kim focused the Gap Analysis Process on these critical systems: API/Raw Materials, Change Control Program, Complaint Program, Self-Inspections, Product Quality Review. Material Management Program Documentation & Records, Validation, and Contract Management. Are we building in times of reflection on potential gaps in our operations?

Key Learnings to Set Up Stability Studies at CROs

Stephanie Ferrari

Stephanie attributes success to attention to Details, Documentation and Communication. She highlighted the following as critical to succeeding when engaging a Contract Research Organization:

  • Establish details and expectations going forward
  • How data will be reported
  • When to notify of OOT or OOS results
  • Reach out with questions rather than assume
  • Know the procedures (e.g., pulls windows, investigations)
  • Eliminate custom report and manual entry for reporting results
  • CRO provides reports directly from their LIMS
  • Client empowered to speak directly with CRO stability team
  • Establish regular meetings to check in on stability studies & discuss any concerns
  • Collaborate on protocol revisions, investigations, study reports

How Can Water in Your Lab Derail Your Analytical Results?

Antonio Hernandez-Cardoso Senior Principal Scientist, USP

Antonio covered the many uses of water in the pharmaceutical process, the various grades used and what can happen to contaminate our water before and during use.

Why is Water Important?

  • Raw material · Solvent · Ingredient · Reagent · Cleaning agent (hot water or steam)
  • Sterile waters – Sterile Water for Irrigation – Sterile Water for Inhalation – Sterile Purified Water – Bacteriostatic Water for Injection – Water for Hemodialysis
  • Packaged waters – Purified Water for small volume use

Our policies and procedures should govern all aspects of how we control and use the various grades of water required in our operations.

Revision of the ICH Q1 Guidelines: The Future of Stability Studies

Lori McCaig (Seagen Inc.)

Lori provided the basis for the current ICH Q1 revision efforts, citing:

  • Modernization in a Global World
  • Operating with a Science & Risk-Based Paradigm
  • Having a Bigger Toolbox
  • Utilizing a Life-cycle Approach to Stability

The process has progressed through Concept Paper and Business Plan with Draft Guideline moving toward the Public Consultation Phase. Many of us will be able to comment indirectly through various organizations in which our companies participate. Watch for these opportunities. The window for input at your level may be brief.

Effectively Handling Stability Deviations and Investigations

Sherilyn Campie, Director of QC Stability, Coherus BioSciences

Deviations and investigations are common in the stability program but when they are handled timely and systematically, leveraging historical data and tools to identify root cause, it’s possible to mitigate impact, gain product knowledge and facilitate continual improvement. To achieve this, Sherilyn highlighted the details involved in:

  • Clear procedures
    • Requirements are general and product-specific
    • Requirements based on level of risk and impact
  • Effective quality system
    • System for trending, detecting, investigating, documenting, and preventing deviations
  • Timely documentation of events
    • Assess and mitigate impact
  • Appropriate resources and processes
    • Training (conduct investigation, technical writing) access to system

How to Graph and Analyze Data for Decision Making

David Lavrich, Ph.D., Senior Principal Scientist, Merck, Inc

David explored understanding the impact of statistics and how data can be evaluated, especially homing in on the adage that a picture is worth a thousand words. Are we satisfied that we have the right resources to tell the right story about our data in the right way?

  • How human perception affects the way our brains interpret different kinds of graphs
  • What types of data are available
  • Common types of errors in graphs, and how to avoid them
  • Selecting the appropriate tools for data analysis and data presentation
  • Using Statistic tools to evaluate and monitor data for decision making or verification
  • Selecting the most effective graph type to display and analyze your data in various scenarios

Setting and Evaluating the Performance of Specifications

Kayla Woodlief, Director Stability & Data Analytics, VIR

Kayla emphasized the critical role that specifications play in our processes and how to establish and evaluate them. Do your operations stress dynamic treatment of specifications across all phases?

  • Inputs into Specification
  • Role of Stability
  • Statistical Methodologies
  • Working with Limited Datasets

Stability of Combination Products – Utilizing Worst Case to Apply Bracketing & Matrixing Study Designs

Laure L. Larkin, Associate Director Global Product Stability, Ethicon R&D Analytical Evaluation

Laure highlighted the recent changes in “Worst-Case” regulatory language/understanding and how it impacts design of stability studies, particularly with regard to bracketing and matrixing study design. Is your understanding of “worst-case” matching with the latest trends in regulatory bodies?

  • Regulators, Standards and Worst-Case
  • Curing our US Fear of Worst-Case
  • Using PAT & Quality by Design (QbD) Concepts for Stability
  • Critical to Stability (CtS) Factors
  • “Simple” Bracketed Design
  • “Optimized” Bracketed Design

The Cost of Human Error And how it impacts Laboratory Management

Matthew LaPierre, Jackson Scott Consulting

Matthew had a very thought-provoking exploration of the myriad of causes that work their way into corporate environments to bring about costly setbacks and how management can effectively reduce these factors. Can we identify with those environments?

  • Slow down.
  • End the blame game.
  • Handle bad news better.
  • Be aware of stressful environments.
  • Get rid of the, “Let’s just get it done” attitude.
  • Full awareness of problematic equipment or methods.

Forced Degradation and Stress Study to Support Specificity in Validation

Min Xia

Min presented the what, why and how of forced degradation/stress studies and the critical information they produce toward the success of stability studies. Do all of our staff understand these concepts and use this information effectively?

  • What is a forced degradation study and why is it required?
  • When should a forced degradation study be performed?
  • What are the stress conditions and their criteria?
  • Peak purity and mass balance, and what do they mean?
  • Method optimization

Stability Studies to Support Vaccine Products

Stephanie Ferrari

Stephanie explored those differences in Vaccine stability studies that enable this product type to reach the market despite the challenges presented by this product form.

  • Multiple active ingredients
  • Released intermediates
  • Adjuvants
  • Different storage conditions
  • Different analytical tests
  • Different regulations and/or expectations

Understanding FDA’s Revised OOS Investigation Guidance

Emily Purchase, Quality, Compliance & Regulatory, CAI

Emily reviewed how this guidance for industry provides the Agency’s current thinking on how to evaluate out-of-specification (OOS) test results. Have you reviewed the revised OOS Guidance?

  • Do we have assurance of understanding with our interpreting investigation results and when to expand the scope of the investigation?
  • Do we know when additional laboratory testing is appropriate along with reporting testing results?
  • Do we know what “cautions” or actions (Field Alert Reports) are required as a result of a confirmed OOS?

Conducting Shipping Studies to Support Product Distribution

Kayla Woodlief, Director Stability & Data Analytics, VIR

Kayla explored major shipping study challenges and how to evaluate each. How do you measure up against these study aspects?

  • Visual Inspection – TOR allotted to visual inspection activities at DP manufacturer
  • Labeling – TOR allotted to labeling drug product at Finished Good labeling sites. Consider TOR allocated to device assembly
  • Product Distribution – Distribution of material from drug product manufacturer to end user. Includes number of shipments & pack/unpack activities.
  • Temperature – Defined temperature for storage & shipment of material, including climatic zones
  • Patient Allowance – TOR allowance for at-home administration / patient convenience
  • Temperature Excursion – Requested time allotted to support temperature excursions during shipment & storage

Assay Transfer, Qualification, Validation – Are We Living in a ‘Land of Confusion’?

Min Xia

Min provided an overview that defined method transfer, method qualification and method validation, helped us understand the differences, and how to use a Phase-appropriate approach for each of their intended purposes, taking into account time, cost, and method lifecycle management.

Phase-appropriate Stability Programs

Lori McCaig, Seagen Inc.

Lori gave a thoughtful examination of the types of stability information needed in each of the product life phases. Moving through project and product lifecycles brings a wide variety of tests and studies. Have we thought of everything in the initial planning stages?

  • Non-clinical development and laying the foundation
  • Early to mid-clinical development and acquiring deep stability knowledge
  • Late clinical / registration phase
  • Commercial phase and lifecycle

Applying & Mastering Stability Statistics

Laura Pack, Sr. Director, QC & Statistics, Rezolute, Inc.

Laura emphasized the importance of carefully assembling the right research questions for stability initiatives to target the data necessary for product information and successful registration. It’s not uncommon to find that many of us have a haphazard approach to assembling our strategies toward stability statistics. How would you evaluate your game plan? Consider some of these objectives:

  • Expiry / Storage Limits
    • Established retest / expiry period?
    • Can retest/expiry be extended?
    • Allowable exposure to non-recommended conditions?
  • Trends
    • Trend on stability?
    • Individual result in trend?
  • Acceptance Criteria
    • Appropriate stability acceptance criteria?
    • Probability of an OOS result before expiry?
  • Similarity
    • Similarity/comparability of different [scales, formulations, presentations, etc.]?
    • Similarity of manufacturing sites?
    • Justification of bracketing / matrixing strategy?

Investigating Microbiology Out of Specification Results: Different than Chemistry

Anthony Grilli, MS, Laboratory Director CEO, FOCUS Laboratories

Anthony enlightened the group about the unique requirements of microbiological testing. There are marked differences in equipment, procedures, and test methods. Is there a direct connection between your Stability Group and the microbiology lab? You are important stakeholders to each other.

Microbes will:

  • Discrete particles
  • Will Die or Will Grow or Might Mutate
  • Hazard is less clear
  • Detectable with technology – but which?

Result: Manual methods and therefore manual documentation that are technique sensitive but may involve several people over time where an OOS may not be known for weeks.

Focus Topics

The focus topics included six breakout sessions with facilitators for open discussion.

Each topic group met individually and after a brief overview of the topic area by the facilitators, participants raised questions about topic issues, shared challenges, and solutions from their experience. These sessions are the essence of a Pharmaceutical Stability Discussion Group meeting, maximizing the exchange of stability knowledge and experience as applied to the various problems encountered by Stability professionals.

Topic 1: Living (well) with your Stability Chambers

The selection, care and monitoring of chambers are critical to our process. Participants had a great variety of problem-solving experiences to share.

Topic 2: Achieving Sample Control Best Practices

The movement and tracking of samples in and out of chambers, laboratories and worldwide sites create a myriad of opportunities for errors, but also for ingenious and compliant solutions.

Participants expressed their frustrations in this area as well as some ingenious practices to overcome the challenges.

Topic 3: Shipping, Excursions, and the Shelf Life “Budget”

Stabilitarians go to great pains to predict product shelf life under well-defined parameters. Predicting how fast and under the varied conditions of production and commerce the product will expend that shelf life is an even greater challenge. Recent developments are making this process a bit easier. Good data in the hands of a skilled statistician goes a long way in assembling a product stability budget.

Topic 4: Stability Statistics and Reports that Clearly Represent Product Stability

Telling the story of your product in numbers and trends is the objective of our Statistics Group in supporting the Stability Function. Establishing a relationship and a plan with your statistical folks is the first step in achieving that objective. Do we have those two foundations in place as we generate our test results in moving toward a regulatory submission?

Topic 5: Laboratory Information Management Systems for Stability

LIMS have the potential to make our lives easier through processing, documentation, data analysis and reporting, but without careful planning and implementation, can introduce more problems than they solve. Participants explored their best practices in establishing user requirements and working as a team with the supplier, quality, IT, and user groups.

Topic 6: Stability Studies at Contract Research Organizations

Participants had many stories of successes and failures in their CRO experiences. The common thread for success was communication, planning and even more communication. Some CRO’s went above the call and supplied expertise to fledgling operations that hadn’t yet fully developed their practices to harness the full benefits of Contract Research Organizations.

The remainder of the PSDG Meeting topics will be discussed next month’s StabilityHub Newsletter.

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A stabilitarian encounters new situations every day. StabilityHub’s discussion forums give Stabilitarians an opportunity to ask questions and offer solutions to specific scenarios. Join in the conversations with other Stabilitiarians and share your knowledge!