24 November 2022
Over the last 10 years, there has been an important change of focus in pharma towards biotech products and personalised therapies. These important new treatments are now emerging into manufacturing, with implications for the way that quality is monitored, managed and assured. Dr Eduard Cayón sets out some practical advice.
As the emphasis of new drug development gravitates towards new, ground-breaking therapies and vaccines, the requirements of manufacturing sites, equipment and processes need to be appropriate for this new environment. For young biotechs, scaling up production brings green-field challenges, while for more established pharma a shift may be required to ensure that facilities are optimised for new ways of working.
Across all of this is the criticality of compliance with Good Manufacturing and Good Distribution Practice (GMP/GDP) and of a fit-for-purpose quality system. Engineering or redesigning facilities without due consideration of what is needed, of what may be superfluous, or of how systems and processes will be validated over time, could lead to costly remedial action and delays in getting important and premium new products to market.
Beyond adapting existing sites or engineering new facilities geared to modern drug production, biopharma companies also need to be more cost-conscious than ever before, in how they run and monitor their manufacturing and supply chain operations. That is because of the relative expense of emerging therapies and the pressure on pricing for continuing product lines.
Gearing up for efficient, optimised and compliant production at scale in a cost-sensitive, biopharma-first world, means creating an environment in which quality can (and must) serve as a real-time facilitator of first-class manufacturing, rather than controller and after-the-fact corrector of production and supply chain delivery.
So what might that look like?
Historically, some pharma quality systems were put in place largely to help pass inspections, rather than to foster innovation by adding inherent value as part of the production process. In such cases, systems existed on the periphery of manufacturing, generating after-the-fact documentation rather than being an integral part and enabler of proceedings.
Today, manufacturers have an opportunity to be more discerning about the measures they put in place to ensure and track quality, and to embed quality management much more within real-time processes where it can more tangibly add value.
This presents a chance to be smarter about the level and scope of detail captured, for instance, and to gear at least some of the tracking, analysis and issue-flagging to enabling internal efficiency gains, by digitalising workflow management and applying intelligent process automation.
One of the drivers of the shift in quality in biopharma manufacturing is the evolving regulatory climate which – in an attempt to be more supportive of innovation – is shifting towards risk management and health authority approval based on the given risk profile. This contrasts with the approach of 20-plus years ago, which favoured indiscriminate documentation, vetting and validation of every small detail against a positive list of requirements, for the sake of being thorough.
Today, as long as biopharma manufacturers respect and show commitment to the principles of GMP and can show they are doing all they can to minimise any risk to the patient (the ultimate goal of pharma quality and safety measures), they can design their facilities and processes to be more fit for purpose, aligned with the respective risk. (Currently, regulators are adapting their assessments and inspection criteria accordingly, not least by bringing on board new generations of inspectors.)
The ‘relaxing’ of inflexible quality-related regulatory requirements presents an opportunity for manufacturers to use systems and measures to their own operational advantage (without compromise to safety, of course). When they apply digital solutions, this should be not just to replicate old, manual processes, but to enable process redesign and process optimisation.
First, however, companies must refresh their process knowledge, enabling them to challenge existing ways of achieving something and analyse the risk of doing it differently.
That might involve redesigning everyday processes to be more efficient, or questioning which products are made at all – and which (eg, lower-margin/loss-making assets) might be better being produced through a subcontracting arrangement.
Certainly the opportunity now is to improve processes, prevent issues from arising in the first place and to share findings and knowledge with key decision-makers, so that problematic processes can be redrawn to be more efficient.
Maximising the potential is not only a matter of digitalisation; there are organisational considerations, too. For instance, if quality teams ordinarily work during standard office hours, eg, 8am-5pm, yet plants operate 24/7 across three shifts, it follows that quality will be ill-equipped to proactively prevent issues or intervene swiftly if an incident occurs when the function is offline.
An optimal solution to this would be to put quality on the shop floor and make the function more integral to production processes, enabling more continuously monitoring; an active real-time role in solutions and recording of decisions as they happen (saving a protracted quality review after the fact). This in turn will increase the likelihood of a timely release.
New biotechs, emerging from the labs into commercial-scale production, have a greater advantage with all of this, not being influenced or unduly held back by legacy quality processes. As they establish full production facilities, they have a chance to incorporate quality ‘by design’ (QbD) building, harnessing emerging best practice and applying risk management to determine what scaled-up production should look like in the 2020s, and what process weaknesses to avoid to achieve frictionless validation.
Moving straight to highly integrated and digitalised processes, which allow for real-time data to flow to where it’s needed and trigger next actions, can significantly heighten the chance of success – affording clear visibility across production and creating the potential for automatic alerts, reminders and prompts based on given parameters to keep everything fluid and dynamic.
From building management systems and equipment control software, to process monitoring data, to sampling and certification of analysis systems, companies have a plethora of tools available to them now to perform optimally and to capture all the data they need to satisfy regulators and auditors.
As they strive to become more proactive in quality management, to support ongoing innovation, companies can also link current systems to historical databases to discern any patterns in deviations/incidents and take positive, preventative action to ensure the same issues won’t recur.
The more that functions, systems and processes can be interlinked, the greater the scope for improvement, too. Connecting historical incident data to risk management for process optimisation, and ERP systems for materials management, offers production and quality teams optimal scope to stay ahead, while also reducing the number of review cycles (on the basis that if a computerised system has been validated, it can be trusted).
With so much great innovation happening at a biopharma product level and so much price and cost sensitivity in today’s markets, biopharma manufacturers cannot afford to be held back by excessive red tape, unwieldy processes, or siloed teamwork. Fortunately, it does not have to be like that – as long as good practice starts with the right advice.
Dr Eduard Cayón is an experienced pharmaceutical industry consultant at bespoke technology and manufacturing supply chain compliance consultancy TDV. He is also the founding partner, VP and a director of pharma auditing organisation Asociación Fórum Auditorías (AFA) in Barcelona. The two organisations recently merged with Rephine Ltd, to create the leading global force in GMP audit services.
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