Let's be clear: the title of this article is a bit tongue-in-cheek. While it might sound like a guide to manufacturing mishaps, it's actually quite the opposite. Inspired by the rom com How to Lose a Guy in 10 Days, this article aims to spotlight the critical missteps that could lead you to "lose a batch" during the manufacturing process. By identifying these pitfalls, I hope to guide you toward best practices that will not only save your batches but also improve the quality, efficiency, and reliability of your operations. So, let's dive in and explore the five things you definitely shouldn't do unless you're keen on courting disaster.

1. Don't Spend Time Building Quality Documents

Create Tools That Facilitate Technical Transfer

Technical transfer in biotech manufacturing refers to the process of transferring scientific methodologies and procedures from one part of the organization to another or between different organizations. It's a critical phase where a product or process moves from development to production or from one manufacturing site to another.

The process involves a comprehensive understanding of the product, its components, the required equipment, and the specific environmental conditions necessary for production. It's not just about transferring information; it's about translating that information into a new context, ensuring that it can be replicated with the same quality and efficiency.

Building and maintaining quality documents for a process requires collaboration across various departments, including R&D, quality assurance (QA), manufacturing, engineering, and regulatory affairs. Manufacturing organizations are like the human body; several different systems are operating within one location to achieve the same goal. When these systems no longer speak to each other or overlook how one might affect the other, there will be a breakdown. Open and transparent communication is key to successful collaboration. Regular meetings, clear guidelines, and defined roles and responsibilities help in aligning everyone toward the common goal. How long should someone take to review a document? What part of the document should each function review? How will delays in tasks be managed?

Tools like collaborative document platforms can facilitate real-time editing, commenting, and tracking changes. This ensures that everyone has access to the latest version of the document and can contribute effectively. Once generated, bring the documents to the cleanroom and have the manufacturing teams perform a read-through. Do the instructions make sense? Are they in the right order? Would a picture of a setup help with consistency? Is it clear what and where information needs to be recorded? Return the marked-up version to the document workflow and now you have not only prepared the team as to what the process looks like, but they are confident they can execute the tasks within.

Impact of Poorly Crafted Documents

From format to instruction, poorly crafted documents can have a domino effect on the entire manufacturing process. Incomplete or ambiguous documents do not provide a solid backbone for training. Lengthy paragraphs filled with background and instruction will only increase the cognitive load on the individual reading it. They are more difficult to revise once the process is in full swing. And they can reduce the confidence levels of those using them. All of these are error traps in the making, which will increase the likelihood of deviations.

2. Don't Analyze Deviation/Nonconformance Data

Success is Hidden in Failure

I have seen it many times before: deviation metrics are generated that drive the practice of quick closures over investigation. The majority of organizations want as few deviations as possible, and rightfully so. But often the desire to have better metrics and reduce open records leads to ineffective investigations and CAPAs. Once closed, they are out of sight, out of mind. This can be dangerous and wasteful, as an average event can exceed tens of thousands of dollars. In order to determine the right pathways for success, we need to examine the pathways of failure.

Deviation or nonconformance records serve as diagnostic tools for your quality management system and are a treasure trove of insight. Understanding the types and frequencies of events can help in assessing the risk levels associated with different stages of the manufacturing process. Even across different products, commonalities can be found that point to gaps in knowledge or mental awareness. Regularly review open and closed records to look for patterns. Are there specific periods (weekly, monthly, quarterly) where recurring deviations or seasonal trends can be identified? Is there a spike in GDP failures during the summer months or on Fridays? Is there a specific piece of equipment or step in the process that is continually associated with events? What CAPAs have been implemented? Are they being reviewed for efficacy?

Let's consider a hypothetical scenario in a manufacturing facility that produces a range of monoclonal antibodies. Over the past quarter, there has been a noticeable increase in deviations related to the purity levels of the final product. The deviations are sporadic but have occurred across multiple product lines.

Step 1: Data Collection

• The QA team collects all deviation reports related to purity levels for the past six months. This includes data on the batch numbers, operators involved, equipment used, time of occurrence, and any immediate corrective actions taken.

Step 2: Data Analysis

• Time-Based Analysis: The team notices that most deviations occurred during the second shift, between 4 p.m. and midnight.
• Equipment-Based Analysis: Two particular bioreactors are consistently linked to these deviations.
• Human Element: The deviations often occur when temporary staff are operating the equipment.

Step 3: Root Cause Analysis

• The second shift has a higher proportion of temporary staff who may not be as well-trained as the regular staff.
• The two bioreactors in question have shown signs of wear and tear in their logbooks but haven't been flagged for maintenance.

Step 4: Implementing New Controls

• Training: A new training module is developed, focusing on the specific operations related to purity control. All operators, including temporary staff, are required to complete this training.
• Equipment Maintenance: The two bioreactors are scheduled for immediate maintenance and calibration. Going forward, a more rigorous preventive maintenance schedule is implemented.
• Real-Time Monitoring: Sensors are installed to provide real-time data on purity levels, allowing for immediate intervention if levels start to deviate.
• Shift Handover Tool: A simple form is introduced to ensure better communication between shifts, particularly focusing on any issues that could impact purity levels.

Step 5: Monitoring and Feedback

• KPI Tracking: Key performance indicators (KPIs) related to purity levels are closely monitored.
• Feedback Loop: A monthly review meeting is set up involving QA, manufacturing, and maintenance departments to discuss the effectiveness of the new controls.

3. Don't Invest in Training

Benefits of Educating and Upskilling Employees

Biotech manufacturing is not a simple assembly line job. It involves an understanding of biological systems, chemical interactions, and quality control measures. Operators often have to make real-time decisions based on a multitude of variables. This level of complexity demands a more robust training approach that goes beyond just reading and understanding a document. Reading a document often doesn't provide the context in which a particular procedure or operation takes place. Without seeing the bigger picture, it's easy for operators to miss the significance of each step, leading to potential errors. Reading alone lacks active engagement, which causes retention to plummet, making it more likely crucial information will not be processed past short-term memory. Most importantly, while reading the document, the individual has no immediate way to clarify doubts or correct misunderstandings. This gap can lead to the perpetuation of errors. While every task does not require hands-on or classroom learning, training on critical tasks and complex equipment should include a mix of styles.

In the 2023 LinkedIn Workplace learning report, 1,579 L&D and HR professionals across the globe were surveyed about the state of learning and development. Among the top five factors people consider when changing jobs include ‘opportunities for career growth within the company’ and ‘opportunities to learn and develop new skills.’ This percentage was highest in the age group 18–34. The next generation of workers, often referred to as Generation Z, fall into this age group and have specific expectations regarding training:1–3

• Personalize it: They value training that is tailored to their individual needs, interests, and career goals.
• Technology is cool: Growing up in a digital age, they expect training to be accessible through modern platforms, including online courses, mobile apps, and virtual reality.
• Continued education: They seek employers that offer ongoing learning and development opportunities, not just one-time training sessions. Implement regular assessments and provide constructive feedback to gauge progress and identify areas for improvement.
• Have options: They prefer interactive and collaborative learning experiences, such as group projects, peer feedback, and social learning platforms. Provide various learning formats, such as in-person classes, online modules, and blended learning, to accommodate different learning preferences.
• Consistent reminder of the mission: They are more likely to engage in training that aligns with their personal values and the broader mission of the organization. In the same LinkedIn report referenced above, aligning learning programs to the business goals is the #1 priority.

Investing in employee training is not just a matter of compliance or ticking the box; it's a strategic move that enhances productivity, quality, and employee satisfaction.

4. Don't Coach and Correct to the Standard

Focus on the Behavior

Coaching and correction are not about micromanagement; they are about guidance and growth. Lack of oversight can lead to complacency and deviation from established standards. Regular coaching ensures that everyone is aligned with the company's goals and adheres to the required procedures. Without it, small errors can snowball into catastrophic failures. If you’ve ever played a sport, have a child in sports, or watch sports, you know how important the coach is to the team. They recognize strengths and weaknesses among the players, set clear roles and responsibilities, and even inspire greatness. Yes, they make sure the rules are followed, but they also directly home in on the behaviors or techniques that are keeping someone from succeeding. Coaches know stronger individuals make a stronger team.

The most important thing to remember when providing coaching is to focus on the specific behavior that needs correction – not the individual. Try to address the behavior immediately. Prompt feedback ensures that the behavior is fresh in the employee's mind, making the coaching more effective. Clearly articulate what is expected and why the current behavior is problematic. Provide examples of desired behavior and identify the necessary tools, training, and support the employee my need to make the required changes. Regularly check in with the employee to assess progress and provide additional guidance as needed. If possible, acknowledge and reward improvements in a group setting, reinforcing positive behavior.

Understanding the Habit Loop

The renowned psychologist William James once said, "All our life, so far as it has definite form, is but a mass of habits." Habits are formed through a loop of cue, routine, and reward. It's far more efficient to instill good habits from the start rather than trying to correct bad habits later. Forming new habits requires creating new neural pathways in the brain. This takes consistent effort and repetition. This is why coaching and support are vital when there are new processes or changes to a process, as setbacks are common. Encouragement and guidance can make the difference between success and failure.

Breaking a bad habit requires understanding the cue, routine, and reward loop and finding ways to disrupt it. It is neither quick nor easy. It requires a deep understanding of human behavior, patience, and a commitment to continuous improvement. As the quote from William James reminds us, our lives are shaped by our habits. In the context of manufacturing, those habits can mean the difference between success and failure and quality and mediocrity.

Investing in coaching and correction is not just about fixing problems; it's about building a culture of excellence, where good habits are nurtured and bad habits are nipped in the bud. It's a long-term investment that pays dividends in productivity, quality, and employee satisfaction.

5. Don't Perform Periodic Reviews

A Stitch in Time Saves Nine

When I speak about periodic review here, it pertains to two things: in-process documentation used to record data and procedures used to execute the process. Let’s start with in-process documentation. Regular review of logbooks, batch records, forms, etc., ensures that errors are caught early and corrective actions are taken before they escalate. This should be done by all shifts, both incoming and outgoing. Simple data transcription errors that aren’t caught can result in delayed batch release or, worse, the loss of a batch because a process decision was made based on the incorrect value. If you have taken the time to develop quality documents (see #1), review will be much easier. There are very simple ways to foster good document review behaviors including checklists, reading aloud, comparing with standards, or including cross-functional teams in review of critical tasks and values before moving forward. In-process documentation should be built into the workday, giving people adequate time to perform it, or else it may not get done.

With regard to procedures, there needs to be a formal process for review and revision. High-functioning organizations implement semi-annual or annual reviews of frequently used procedures to ensure they are up to date with cGMPs and other regulatory standards. This does not have to be a lengthy process. Instead, empower the users of the procedures to keep a running list of potential updates they would like to see to make the document more usable. If the current revision of the SOP cannot be followed, redline it until it can be formally revised. Do not rely on tribal knowledge. Documentation in our industry is a living entity; it evolves and changes. It tells a story that must stand the test of time. Through periodic review, we can ensure the story’s evolution is accurate and meets the expected regulatory standards.

Quality documentation, data analysis, training, coaching, and regular review of documentation are not just best practices; they are essential to the success of any biotech manufacturing operation. By embracing these principles, you're not only safeguarding your batches but also contributing to a culture of excellence and integrity. Don't lose a batch in 10 days; instead, build a legacy of quality, innovation, and success.

References

LinkedIn Learning. (2023). 2023 Workplace Learning Report. Retrieved from LinkedIn Learning: https://learning.linkedin.com/resources/workplace-learning-report#2

Oswald, R. S. (2022, September 14). The 4 crucial expectations Gen Z teams have for the workplace. Retrieved from Fast Company: https://www.fastcompany.com/90784200/the-4-crucial-expectations-gen-z-teams-have-for-the-workplace

Zoe, E. (2021, February 22). Training Gen Z employees: 8 best practices. Retrieved from Talent LMS: https://www.talentlms.com/blog/training-gen-z-employees/

About The Author:

Sarah Boynton is a consultant on the Quality Executive Partners (QxP) team. She has extensive experience in the biopharmaceutical/cell and gene therapy space, with a particular focus on cGMP training, human performance/error prevention, downstream processing, and non-conformance investigations. Prior to joining QxP, Boynton worked for Catalent Pharma Solutions, KBI Biopharma, AstraZeneca, Med Immune, and GlaxoSmithKline.

Link to original article at Pharmaceutical Online: https://www.pharmaceuticalonline.com/doc/how-to-lose-a-batch-in-days-0001