Ten Things Every Stabilitarian Should Know

My Stability career started at the bottom, a lowly Assistant Formulator who submitted our latest attempts in constructing a palatable medicinal liquid that would stand up to 40C for 6 months; products had it tougher back in the early days of alchemy. Finally, after making the team and years of watching the supervisors function at survival levels, I was made a provisional supervisor facing two years of management responsibility without the title or higher salary because they really wanted you to prove you could do it before you received the compensation. My, how times have changed! Here are a few things I learned along the way toward building a successful Stability Group/Department. Our hope is that you may find some useful tactics here for your Stability organization, whether you are a manager, supervisor, or supporting group member.

Knowing how regulators are interpreting and applying requirements, how industry is complying/not complying/responding, and what measures are being taken to shape best practices and emerging guidelines is among the most valuable resources a Stabilitarian can possess.

1. Industry Stability and Quality Intelligence is worthy of a major staff objective, with communications and updates to the Stability Operations Group on a regular basis.
2. On-line newsletter subscriptions, websites, webinars, discussion groups, seminars, meetings, associations, etc. are at a critical components in gaining a good understanding of the external factors impacting the Stability Function.

• How Stable is Your Stability Knowledge

Stability is a worthy organization, deserving adequate resources; human, equipment, and support.

Our newly created Stability Group was chronically shorthanded and pleas for sufficient staffing were answered by dumping castoffs, walking wounded, and technically obsolete folks into the Stability area. On the equipment side, Stability Chambers are big ticket items never well received in departmental budgets when monitoring systems and continuous rounds of validation siphon off their share. Sometimes delays in purchases can result in multiple equipment emergencies that overwhelm a budget which precludes the purchase of other needed resources.

1. Establish close relationships with the Quality and HR Groups so they understand the critical role of Stability and necessity of highly competent individuals with no room to carry those who can’t contribute to the mission. Also, establish very specific requirements for appropriate experience, training, and education to set a high and clear standard for those accepted into the group.
2. Set up a well-timed ladder of equipment purchases so that most failures are precluded. Use the example of 483s and Warning Letters concerning equipment GMP and compliance failures to emphasize the necessity of well-maintained, high performing equipment.

• The Importance of Stability Testing in Pharmaceutical Development, QbD Group

Having a Stability Group would seem like a basic requirement for all companies, whether real or virtual, and being separated from a Stability Group outside of personal plans never would cross your mind. However, out of the 5 companies I have served with, three have dissolved their Stability Group and four needed me elsewhere, both inside and outside the company for an amazing variety of reasons. Stability organizations and careers should not be taken for granted.

1. Make it second nature to be an ambassador for Stability Operations through stakeholder relations, telling useful stories, staying on top of your audit game, continuously improving metrics, and maintaining a presence at the corporate table.
2. Promote National Medical Product Stability Day (Feb 19). Order a cake for the corporate masses and tune in to the “televised” celebration.
3. Attend a conference, discussion group, or seminar and bring back some big news to splash throughout your hallowed halls.

• Medical Product Stability Day, 2024 Online Celebration
• How Stable is Your Stability Knowledge

Success in the Stability Process does not rest solely within the Stability Group. In addition to delivering information and support to a variety of stakeholders, Stability relies upon a wide array of stakeholders for critical input. Therefore, investment in stakeholder relations is a high priority for a Stability Group.

1. Managers will do well to enlist their staff in developing clear lines of communication and understanding the needs of stakeholder partners. Each Stakeholder should have a Stability Group ambassador to promote these efforts
2. Coordinating SOPs and operations, establishing audit support expectations, specifying the timing of deliverables and exchanging ideas for continuous improvement are the key deliverables between Stability Operations and their stakeholders.

• The Stability Village People

While somewhat functionally forgiving, Sample Control & Inventory are key GMP factors and lightning rods for inspections and audits. Because it has been historically easy to maintain operations despite a modest number of errors in control and inventory, these areas often received low priority in guaranteeing accuracy. In the past decade or two, they have been low hanging fruit for inspections.

1. A well-documented chain of custody is the best evidence of sample control to present to regulators and auditors. Sample errors, whether of identity, quantity, location, or bearer/receiver should be trended and continuously reduced.
2. Inventory is prone to inaccuracies through failure to properly document non-routine withdrawals. Conducting an inventory is a challenge because of the fluid nature of sample counts, time required, and disruption to the controlled environment to access samples. There are several methods for maintaining inventory, but the most convenient, accurate, and resource conserving is to update the inventory of each study at the time of sample pull. A further help is to start a study with samples grouped in conveniently counted groupings (for example, 6 bins with 100 samples each and each bin with a tamper-evident seal so that only the samples from a broken-seal bin need be counted individually. This method does not require assigning more staff or disrupting the controlled environment. In theory, every study is inventoried at least yearly and whenever a change occurs. Any errors are discovered at the time of inventory and no inventory error leaves a chamber.

• Stability Sample Integrity: A Critical Link in the Chain of Custody
• Can You Count on Your Stability Sample Inventory: Building a Reliable System

While audits and inspections have long been perceived as intrusions and impending setbacks, they present the opportunity to catch and remediate problems before setbacks are imposed by others. To miss this advantage is to invite delays, incur extra expense, receive negative press, and risk missing commercialization targets.

1. The best preparations begin with reviewing previous audit findings and conducting a thorough risk assessment.
2. Audit preparation activities should be a regularly scheduled ongoing program involving training, walk-throughs, SOP review, Stakeholder interaction and planning and periodic mock audits.

• A Step-by-Step Guide to Internal Quality Audits

While Budget concerns are generally relegated to a phrenetic day or two annually in the life of a Stabilitarian, the lack of a regular diligence can have a real negative impact on the Stability Group and Stability Operations in general. For the most part, upper management often neglects to keep budgetary topics in full view of their staff.

1. A member of the Stability Group, supervisor or not, should be tasked with being familiar with the budget process, target dates and deadlines, and keeping the group fully aware of this information.
2. Put a standing budget update item on your Stability Group Meeting agenda and trend budget items for Group awareness and action when needed.

• ICH Pharmaceutical Stability Testing and Storage, Intertek

Resource constraints are always a factor in Stability Operations, as research questions and commercial targets evolve, overwhelming available space, departmental budgets, and personnel overtime hours. Requests for conservation abound and there are a few options available.

1. Engage regulatory, quality and statistics personnel to identify potential use of leveraging/comparability studies to minimize the overall number of studies applied.
2. Similarly, engage professionals to utilize tactics such as matrixing and bracketing to reduce testing.
3. Establish stringent restrictions regarding keeping samples after a study has been completed or put on hold.

• Risk-Based Predictive Stability Feedback from IQ Working Group Regulatory Sub Team
• Lean Stability Case Studies

Employee turnover is most often a result of poor management, lack of enrichment, and no apparent path of advancement.

1. Make sure that staff members have objectives that go beyond the basics of their job description and match their talents and aspirations. Many potential objectives can be extracted from the Key principles noted in this article.
2. Create in-group promotion levels and titles as stepping stones between established corporate titles and define requirements to achieve these intermediate levels.

• When Things Cool Down, There May Be Opportunity for Growth

The Stability Function generates a lot of data, collectively known as Product Knowledge. Some data that supports storage conditions and shelf life make it into a regulatory submission while much of the rest is not effectively communicated, applied, or stored.

1. Construct a product development/history file where data, decisions and justifications build an ongoing story in a logical, searchable sequence.
2. Work with stakeholders to understand their information needs, whether data originates from test results, process outputs, quality-related metrics, or environmental condition monitoring,
3. Create a group objective to identify the Stability Stories you need to tell, who you tell them to, when you tell them, and how they are constructed.

• Navigating Medical Product Stability Information
• Taking Charge of Your Stability Program
• Stability Information Month Results

Beyond the SOPs, protocols, and schedules, there are critical aspects of the Stability Function that are as much finesse as they are science. Mastering these comes with experience, often painful in the attainment, but necessary for success. In the Stability community, shared experiences can help us move forward together more rapidly than on our own. Have you requested information from others or shared your experience lately?