Continuous Process Regulation in Quality Assurance Continuous Process Regulation

Embedded in the manufacturing of pharmaceutical medicines are regulatory regulations and norms. A typical example is the current Good Manufacturing Practices which every new employee learns about its key aspects when joining the on-boarding trainings in a pharmaceutical plant

If both you and your friend decide to bake a cake, how will the cakes look like?

What are the possible reasons for such discrepancy?

Different ingredients used? Different oven, bowl, pan used? Bake with different interpretations from a same recipe? Different recipe used? Different temperature setting? Possibly added too much of a certain ingredient? Different skills?

As per Annex 3 of WHO good manufacturing practices for pharmaceutical products, cGMP are aimed primarily at reducing the risks inherent in any pharmaceutical supply system to secure that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. Even well-designed medicines may become ineffective and unsafe for patients from inefficacy and contamination when companies do not comply to such cGMP regulations.

Similarly, backing pretty, tasteful, and replicable cakes is only possible through the standardization of all aspects of cake making from the starting materials, premises, and equipment to the training and personal hygiene of staff.

For that reason, standard work is one of the most powerful tools in the Continuous Improvement toolbox, as standardization helps define what process steps are, how they should be carried out and how they should perform.

In a nutshell, we create standards to (i) reveal problems for when the process has deteriorated and deviated from its normal state, and (ii) sustain incremental gains for when the current standard enhanced by new ideas becomes the new baseline for further improvements

The change in Pharma

Any action aiming at achieving excellence or troubleshooting deviation that can impair the validated status of a process or modify the qualified status of an equipment in the manufacturing plants must follow such cGMP rules. The proposed change must be formally approved before implementation, and a submission of a dossier variation must be assessed and may be be required for the continued manufacture of the that product depending on the type / criticality of the change.

The board game above depicts in a playful way the bureaucracy we face when modifying processes in the Pharma Industry. My perception is that such bureaucratic control creates an environment with low tolerance for risk-taking, which in turn results in a refusal to use creative solutions or workarounds on the shopfloor. Another consequence is that error-based training approach barely exists, so operators & technicians are trained to conduct their tasks to a high standard based on high-level, boring, and badly written Standard Operating Procedures (it is important to remark that a handful of leading companies has been introducing in their operations advanced technologies like VR to support training and AR for daily operations activities, but we are still far from benefiting from that at full scale and cross sector point of view).

On the flip side, Continuous Improvement folks have the challenging task of instilling the same people with the so called "out-of-box" thinking where creativity and continuous change are necessary to breed innovative ideas and solutions to tackle problems and uplift the shopfloor performance. Given the fact that standardization requires habitual repetition whilst creativity involves continual change, the pretended standardization promoted by cGMP versus the Continuous Change required for manufacturers to keep evolving is one of the biggest "contradictions" that we need to deal with.

A bit of my practical experience

To illustrate how such dilemma is perceived in operations, I share below 2 stories of my own:

1. Novartis Energy Excellence Awards

Launched in 2004, the Novartis Energy Excellence Awards recognized achievements in Energy Management encompassing all business processes focused on keeping the company's energy use and GHG emissions at a minimum.

Back in 2007, I seized an opportunity related to optimizing the packaging design of OSD finished products in order to reduce packaging materials consumption and increase packaging machines output. Given budget constraints and project details, every year we would define a list of products to be enhanced through issuing a "Change Control" request (a key process within the cGMP framework to ensure the execution and compliance of GMP related modifications). Naturally, every year I had to explain why changes were necessary and the related benefits. In the long run, it became some sort of yearly joke:

"– hey Marcelo, is your product list coming out this year or not?"

Time passed by, and in 2012 the scope of Energy Excellence Awards was expanded to Sustainable Packaging where 14 submissions to the 2012 Award Scheme were assessed. To make a long story short, many colleagues got surprised that our site had won the 1st-ever Novartis EEA in Category "Sustainable Packaging", competing with the entire Novartis Group network.

2. Operational Excellence

The second story took place when I was leading the implementation of a global program aimed at reducing lead-times in packaging operations. During the first walkthrough in one of the selected sites along with the local OpEx lead, I pointed out one potential opportunity in the process, when she quickly replied:

"- Oh, Marcelo, we already tried it before, but this idea was not approved…"

In this case, the idea required an "external push" to get the right level of support from the local Quality Assurance so as to approve the necessary risk analysis and action plan. In 6 months, we were able to bring down by 60% the average lead-time.

Final thoughts

As Dr. W. Edwards Deming once said, "standardization allows us to create systems that are reliable and effective. However, within that system there should be a great deal of flexibility to apply creative ideas". Pharmaceutical companies should look beyond the functional requirements of compliance and design an effective change control system that allows companies to modify processes whilst maintaining the validated state of the systems, and a robust and effective CAPA system along with an efficient deviation handling system which evaluates the events according to the associated risk. On the other hand, it is fair to acknowledge that regulations are evolving, vide ICH Q10, so as to facilitate appropriate continual improvement of product quality, quality processes, etc.

It goes without saying that culture change is all about achieving different results through adopting new ways of working. It is imperative for Pharma Industry (e.g. Gx companies) to continuously grasp the full value of people, assets and resources in order to remain competitive and to bridge the new challenges like the increasing cost pressure, demand uncertainty and market volatility, changing product portfolio towards smaller volumes, etc.

And.. what are Your thoughts? I will be more than glad to hear your opinion and to learn from your experience.

 Take care!

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Source: https://www.linkedin.com/pulse/cgmp-regulations-versus-continuous-improvement-operations-costa

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