Navigating the Challenges of a Modern Quality Control Laboratory

The modern quality control (QC) laboratory has advanced significantly in the last 10 years. Fast forward to 2022 and the modern QC laboratory is testing highly complex drug products using a wide range of analytical techniques, instrumentation and software with continually evolving regulations and guidance relating to instrument qualification, software validation and data integrity to protect product quality.

The flexible nature and wide-ranging capability of a modern QC laboratory presents many challenges from a management perspective.

Complex production

Firstly, customers are faced with an increasingly complicated manufacturing process. Exciting advances in modern science have enabled the production of complex drug products that target specific therapeutic areas, but the manufacturing processes and raw materials behind them can be as complex as the final product itself. Some manufacturing processes involve the use of highly reactive components that require careful handling and end products are subject to rigorous testing to ensure these components are removed effectively. As these products become more complex, the QC laboratory needs access to more advanced analytical techniques and instrumentation to ensure the end products meet the desired quality.  

Embracing new analytical techniques

QC laboratories are utilizing more analytical techniques than ever before to provide lower detection limits and accurate quantitation of residual components within drug products.

For example, Raman spectroscopy is being increasingly used in QC laboratories to analyze incoming raw material and formulated products. The qualitative identity testing of raw materials can be performed through the outer container without the need for opening, therefore, eliminating the time taken to sample each batch of material while protecting the integrity of the product until point of use. Multiple formulated product samples such as tablets, capsules, powders, liquids and gels can be analyzed simultaneously, significantly improving productivity and sample throughput without destroying the samples.

Mass Spectrometry (MS) is also becoming a common technique utilized within QC laboratories. Liquid and gas chromatography-mass spectrometry (LC-MS and GC-MS) workflows are much more sensitive than conventional chromatography and therefore can be used to quantify levels of potentially genotoxic impurities (PGI) and genotoxic impurities (GI), helping users to comply with the requirements of International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) S2 R1 guidance.

Other examples include inductively couple plasma-mass spectrometry (ICP-MS) techniques being used to detect low levels of residual metals in drug products to comply with ICH Q3D R2 guidance, and multi-dimensional chromatography being used to separate known impurities that co-elute with conventional single dimension chromatography.      

The challenges of working with multi-vendors

The modern QC laboratory needs a variety of technology to help teams accomplish their work in an efficient and compliant way. We therefore see many different types of instruments from many different instrument manufacturers within the QC laboratory.

This presents a number of challenges for the QC management team:

• Multiple vendors to assess and approve within your quality management system (QMS)
• Individual quality/technical agreements (QA/TA) to agree and implement
• Raising purchase orders for multiple vendors
• Differing service levels (SL) provided by individual vendors with varying costs
• Different maintenance and qualifications strategies that can be difficult to explain during regulatory inspections
• Multiple points of contact for logging repair calls/request for service.

QC laboratories who face the above challenges can simplify, optimize and transform their operational processes by working with a preferred service partner who can support multiple instrument technologies from multiple vendors. For example, you may be able to reduce from 10 individual service vendors to 2 or 3 service partners who can support your complete instrument fleet and keep your laboratory compliant with the current regulations. This approach significantly reduces the management time and associated cost of using individual service vendors while delivering consistency across your instrument fleet when it comes to maintenance and qualification services. Another advantage of using a service partner is that they will generally have the skill and experience to deliver a custom solution based on your specific user requirements and not reliant on individual vendors and their “standard” delivery programs.  

Consolidating software management

QC laboratories also need multiple software platforms to control the various multi-vendor instrument technologies that generate the data to determine whether a drug product meets desired quality requirements. While there is not currently one software platform to resolve this issue, software manufacturers are recognizing the need to work together to connect their individual software platforms and produce a more complete digital workflow. For example, a recent collaboration between Agilent and Mettler Toledo produced a solution in which samples may be prepared in one software platform where the sample weight is digitally recorded. The sample preparation step is completed, and the digital sample weight is then automatically transferred into another software platform that is used to analyze the sample. Connecting the two software platforms eliminates the need for a scientist to manually transfer data between the software platforms, therefore, reducing human error or the potential for data manipulation or falsification.  

All modern software platforms are designed to be flexible and used across many different industries with different applications. Software comes with configurable options that the end-user must select to determine which functionality they will use within their analytical workflow. Once the desired software configuration has been selected, the software must be validated to demonstrate the chosen configuration is fit for purpose and protects the data from potential manipulation or falsification.

Some regulated QC laboratories do not validate their software after initial configuration, or after re-configuration to change the intended use or implement data integrity controls. The lack of software validation in regulated QC laboratories has been highlighted during recent regulatory inspections based on the volume of non-conformances that have been issued on this topic.

Software configuration and validation is a critical component in minimizing compliance risk. With multiple software platforms (typically 10 or more) being used within QC laboratories, a significant workload is necessary to keep software platforms maintained in a validated state. If you have gaps in your software validation knowledge or resources, then your service partner should be able to assist and provide software validation experts who can manage and deliver a validation project for you.        

Ensuring a return on investment (ROI)

Having a fully stocked QC laboratory that contains all the latest instrument technologies and capabilities comes at a cost, but many labs are being challenged to control costs and “do more with less”. Very few laboratories have unlimited budgets to invest in new technology or replace existing instruments on a regular basis. Most laboratories have a high instrument utilization rate with a small amount of spare capacity to cope with instrument downtime. This high utilization rate coupled with limited spare capacity increases risks and can result in breakdowns that have a significant impact on the sample throughput and drug product release rate. Some laboratories are so focused on keeping on top of the drug product release testing that they do not identify problems with instrument fleets until it’s too late, and breakdowns occur.

As a result, instrument manufacturers are developing software that monitors the usage and performance of instruments to provide scientists with data analytics so they can make informed business decisions. Examples include:

• Notification if an instrument stops acquiring data
• Notification when an instrument needs maintenance
• Instrument usage rates on a daily, weekly or monthly basis
• Breakdown/repair data so you can identify problematic instruments (and potentially replace)
• Under-utilized instruments that may not be needed and enable you to downsize you instrument fleet to save money
• Highly utilized instruments that provides you with justification to expand your instrument fleet

Knowledge is power and improving monitoring services allows customers to keep a close eye on their fleet, helping to maintain productivity, minimize downtime and achieve a return on their investment.

Investing in a service partner

There are many challenges to navigate within the modern QC laboratory. From working with multi-vendors, to instrument qualification, software validation and data integrity requirements, to the sample throughput and overall laboratory productivity. The best advice is to seek opportunities that can simplify, optimize and potentially transform your business operations while remaining productive and reducing compliance risk. Look for a service partner that can support multiple instrument technologies and manufacturers and deliver custom solutions to meet your specific user requirements. This will reduce the number of vendors and your internal management workload, while delivering consistency across your instrument fleet, making it easier to meet requirements during regulatory inspections. It is also advisable to consider purchasing software that provides instrument health and productivity data, helping you to make informed business decisions about your instrument fleet and avoid unnecessary breakdowns that can significantly impact your drug product release program. Working with a preferred service partner enables you to simplify your internal process and helps you navigate the daily challenges, enabling you to focus on your drug product release program.

About the author:

Garry Wright is the European laboratory compliance specialist for Agilent Technologies and a member of the Agilent Compliance Council. Garry worked in the regulated pharmaceutical industry for 20 years prior to joining Agilent. His industrial experience focused on development and implementation of quality management systems, good manufacturing practice (GMP) training and compliance auditing. Garry’s role within Agilent is to provide compliance consulting services to Agilent and our customer network. Since joining Agilent, he has regularly presented on topics relating to regulatory compliance, data integrity and instrument qualification at compliance forums.