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Richard Hammond, Chief Technical Officer, Sphere Fluidics.
Introducing new equipment in life sciences typically follows a well-worn path. At first, as a vendor, your new device is picked up by the research community as it enables new experimental approaches or provides new measurement methods. The barriers to entry are relatively low at this point: fundamentally, you need a moderately reliable product that is safe to use. Over time, the technology becomes more familiar, its benefits are clear, papers start to emerge, and a community of users begins to develop.
The applications then start to move away from pure research and your device becomes an integral part of drug development processes. In this evolution, the product may be recognised for its potential within manufacturing workflows. Whilst an exciting next step in the technology’s breadth of applications, this introduces new regulatory hurdles. Suddenly, the acronym ‘GMP’ is everywhere and life is getting much more complicated.
It is important to consider the key challenges in successfully making this shift from research vendor into a Good Manufacturing Practice, or GMP-ready vendor, and the critical areas to prioritise to ensure a seamless transition into this new world. It requires a step-change in maturity of processes, documentation and rigour but with long-lasting benefit to develop high-quality devices more quickly and efficiently.
At the heart of GMP, is a straightforward premise: all drug products sold on the market should be consistently safe and effective from the first batch to the last, and controlling the manufacturing processes is key to achieving this. This underlying principle then extends to become a range of directives, regulations, and guidelines built over many years as the science and technology used for manufacture develops.
As an equipment vendor, the most important concept to grasp is that GMP does not apply directly to you. It applies to the organisation manufacturing and marketing the drug product – your customer. The second most important concept is that GMP is serious. Failure to comply with the various regulations and guidelines has a significant impact, ultimately including the shutting down of facilities and the product being taken off the market. Hence achieving and maintaining GMP compliance is business-critical for your customers and you need to play your part in this. You can’t achieve compliance for your customer, but you can undermine your customer’s compliance – and they won’t be happy if you do.
In a European context, the overarching legislation controlling medicinal products for human use encompasses a number of Directives and Regulations published as EudraLex Volume 1 ‘EU pharmaceutical legislation for medicinal products for human use’. There are then several Guidelines to support the basic legislation – in particular EudraLex Volume 4 ‘Guidelines for good manufacturing practices for medicinal products for human and veterinary use’. The core of Volume 4 is Part 1 – Basic Requirements. These nine chapters encompass the full extent of GMP and are well worth reading to get an insight into what your customers need to do. However, from an equipment vendor perspective there are a number of critical areas to focus on.
Risk Management
The biggest change in transitioning from research equipment vendor to GMP equipment vendor is embracing risk management. The systematic assessment of product quality risk to drive decision making and continuous improvement is a cornerstone of quality management within GMP, as it is recognised as an efficient and effective approach. Within the context of new equipment, the ICH Guideline 9, referenced in Volume 4, makes specific mention that ‘The application of quality risk management to the design, validation and technology transfer of advanced production processes and analytical methods, advanced data analysis methods and computerised systems is important‘.
This change needs to impact your entire organisation. Risk management processes need to be applied to equipment design, testing, manufacture, and customer support. This lets you identify and understand the risks to product quality, take appropriate, prioritised actions to manage the risks, and communicate this clearly to your customer via good record keeping.
Demonstrating fitness for purpose – qualification and validation
Another big change from research to GMP is the substantial level of evidence required to demonstrate the equipment and processes are capable of doing the job they need to do. There are two parts to this: qualification and validation. The first focuses on the equipment itself: “does it meet specification and perform as intended?” The second focuses on the process performed by the equipment, facility and operators: “can the process make the product to the necessary quality?”
Typically, as an equipment vendor, qualification is the dominant area of work with validation conducted by your customer with your support. Qualification includes six well-defined stages starting with a defined User Requirements Specification (clearly stating what the equipment needs to do) through to Performance Qualification (robust evidence the equipment can achieve the necessary performance). Working through all these can take significant time and effort but the customer will expect it and want to be closely involved, so they can be confident your device is fit for purpose and the necessary evidence is recorded.
Computerised Systems
Almost all equipment today includes some form of computerised system – software running on hardware to fulfil certain functions. Such systems have their own guidelines within Volume 4 as they present a unique set of challenges in maintaining quality and performance. Again, a risk management approach is mandated throughout the system lifecycle, particularly to decide the extent of validation and data integrity controls required. User Requirement Specifications are needed to describe the function of the system and these need to be traced through the system life cycle – providing evidence the requirements are met whenever the system is used.
Electronic signatures are allowed, but these must be permanently linked to the respective record with time and date. This then leads to a plethora of requirements about user access to systems and managing data integrity so records cannot be altered. This is a good example of an area where moving into GMP requires a lot more rigour in specifying and validating software to demonstrate compliance with guidelines than a research device.
Change Control
The final big area of change is change control. Here, research and GMP are diametrically opposed in their goals. Research is all about trying new things and making new discoveries; GMP is all about maintaining product quality and managing risk. This needs a change in mindset for the equipment supplier. As a research equipment vendor, rapid updates and providing new ways of doing things are expected. Maintaining this approach will cause your GMP customer a huge headache.
Any change to your device, hardware or software, needs to be thoroughly planned, assessed for risk, and appropriate re-qualification and re-validation performed to show no impact on quality. This then has a knock-on effect for your customer regarding their user training, update of operating procedures, and other validation activities. As a vendor, you need to understand this and implement robust change control and communication processes with your customers.
Making the transition from research equipment vendor to GMP-ready vendor requires changes in how you run your business and interact with your customers. These changes are both practical and conceptual – changing the mindset of your team to understand the challenges a GMP-compliant customer faces. However, the benefits are substantial for both parties: new technology and equipment embedded in drug manufacture, advancing healthcare and helping patients.