30 Years of GMP - A Personal View on Good Manufacturing Practices

Good Manufacturing Practices – my initial encounter: I gained my first experience with quality management in the engineering industry as a young mechanical engineering graduate. I pictured the highest quality standards and wondered what it would be like in the pharmaceutical industry. What standards would apply there? I quickly realised that the ISO guidelines in mechanical engineering were in some respects ahead of GMPs.

The quality of medicinal products was achieved! From today's perspective, not because of the operating procedures, but despite of them. In retrospect and my opinion, this success was based on the dedication and experience of the staff.

I was thrown in at the deep end by my bosses at the time. Little did I know then that my experience in mechanical engineering would in some respects put me ahead of the customers.

My personal view reflects the experiences I have gained from countless visits to companies. They always placed their full trust in me and spoke openly about their problems. After all, as a management consultant, you don't come on board in fair weather, but in rough storms. My clients included small, medium-sized, large, and global companies. I am very grateful that I was and am still able to gain such a deep insight into an industry that is considered to be rather closed.

Many of my companions describe me as an optimist, and in my view that is quite a good prerequisite for entrepreneurship. Even as an optimist you often get disappointed, and that's a good thing!

Dis-Illusionment is positive

Once a “disillusion” has been pushed aside you can see reality with an unclouded view. With preconceptions that you develop over time – incidentally a particular form of operational blindness – you deceive yourself. This is why disillusion is the key for
optimists to see reality. It is similar to pessimists when it comes to surprises. They are not coincidences as many believe, but also the results of realities. It is up to each individual to decide whether to accept these realities.

What has all this got to do with GMP? GMP stands for Good Manufacturing Practice. Why is manufacturing practice just good and not better? Shouldn't we strive for better or best manufacturing practices?

What is special about GMP?

Let's start by comparing mechanical engineering to the pharmaceutical industry. In general, companies should be satisfied if all goes well. Some sectors strive to make their processes better, e.g. through continuous improvement processes. However, the demand comes from customers who are prepared to pay more for better products. Improvement is linked to monetary targets. But no pharmaceutical manufacturer gets paid more if another sensor is installed on a machine.

As a mechanical engineer, I had to learn that one cannot improve a medicinal product or its manufacturing processes in a fast-track manner. The key to GMP compliance is to comply with pharmacopoeias and the information in the respective marketing authorisation documents. There are no different quality levels only the one quality that must be achieved.

Obligation and choice

The fulfillment of the described requirements is mandatory, and this is difficult enough. It becomes even more insurmountable when internal guidelines raise the bar yet higher. In many consulting projects, the aim was to adapt the specifications to reality.

With this in mind, it was obvious at the time to organise the GMP Compliance Adviser in such a way that the authors describe the minimum requirements. The editors' task was to remove the "frills" from the description of specific company processes. This is still the case today. Everyone can do more but leaving out the unnecessary on the other hand is difficult. Michelangelo is credited with a quote about how he created perfect sculptures:

"In every block of marble, I see a statue as clearly as if it were standing in front of me, moulded and perfect in its posture and action. I only have to chisel away the rough walls
that imprison the beautiful apparition to show it to others as my eyes see it."

Quality management is often the same. It is important to eliminate the processes that hinder quality. New processes should only be introduced where they are necessary. Every consulting project and every technical article moves between the two guard rails: formulate exactly what is necessary and leave out what is unnecessary!

And it’s an ongoing task just like tidying up the garage. If I don't do this from time to time bulky rubbish piles up, and one ends up creating living space for unwelcome occupants.

What has changed in the last 30 years and what do I expect for the future?

Let me make a preliminary assessment: I look at Good Manufacturing Practices with a great deal of confidence. The last 30 years have been anything but boring for anyone who has an interest in GMP.

I'll list the most important keywords that have paved my professional path:

• Plant qualification
• Process validation
• Computerised system validation
• GMP for Active Pharmaceutical Ingredients
• Risk analysis - later on risk management
• Process Analytical Technology (PAT)
• Electronic records and signatures
• Lean management
• Six Sigma
• Good Distribution Practice
• Continuous improvement process
• Continued process verification
• Process management
• GMP for combination products
• Quality culture
• ATMPs
• Contamination Control Strategy (CCS)

Some of it stayed some of it went into the archives and still slumbers there.

What has always been important to me and in my view will become even more important are the people involved in these processes. I would therefore like to put a focus on the employees in the future. I am thinking of aspects that are often neglected not only in quality management:

• Trustful cooperation between employees
• Enthusiasm for processes, products and people
• Courage to interpret, to read between the lines
• Valuing people in quality functions such as QA/QA/QC
• Living, demonstrating and demanding a quality culture
• Managing risks, not just assessing them
• Improving the methodological knowledge of employees
• Daily strive for good, lean solutions
• A process and customer focus in every task
• Comprehensible writing when creating SOPs and documents
• A holistic view of the processes

Books have been written on each of these points and they often gather dust on the bookshelf. It would be worth dusting them off and filling their contents with life.

I am convinced that we need more success seekers in organisations. We have too many failure-avoiders in our ranks. They carry their concerns around on big trays and rarely get anything done. We need confident and forward-thinking people who understand the details of the process elements as well as the big picture.

Perhaps you may be wondering why I am looking to the future with confidence?

Thirty years ago, I was given the opportunity to prove myself in a field I knew little about. It took courage on the part of my employers and my clients – and it was well worth it. If you try to hedge your bets and are not prepared to take risks you won't make any progress. And to those who say nothing has improved, I reply: "Take another look at the list above." All of these quality processes/elements did not exist 30 years ago or were rudimentary at best. Many of them have developed and improved GMP.

The next generation of professionals will use much more technology, automation, machine learning, and eventually artificial intelligence to achieve and ensure quality objectives. The challenge of seeing people as the starting point for organisations will remain even as we hand the work over to computers. And here I am confident. Generations X, Y, and Z have different priorities than the baby boomers to which I belong. The future belongs to our children's generation. I see them as highly professional, motivated, and interested in the satisfaction of their fellow human beings.

Conclusion

It makes sense to have GMP regulations because they are essential to the work. Global GMP harmonisation is a success story that will hopefully continue to progress well. As this process is in flux, it is important to know the regulations and apply them with a sense of proportion.

If I may offer some unsolicited advice, it would be this:

"Everyone involved in the design of GMP processes should familiarise themselves with the relevant regulations and learn how to interpret them. The longer I read texts, the more the gaps became apparent. There is often more between the lines than is apparent from the ink on the letters. This is the key to a lean GMP system."
The GMP Compliance Adviser and many other of our GMP publications were created with the idea of making life easier for the readers. The publishing house will continue to do so in the future. In more than 20 years of consulting, I have realised that the individual adaptation to the company’s quality management system is the task of our readers and will probably remain so for some time to come.

I am grateful that I have been able to further develop many GMP systems together with various people and for the benefit of patients. It has always been important to me to convey the meaningfulness and necessity of Good Manufacturing Practices to people - I am also trying to do this with the GMP & TEA webcast series. We are in a position to develop and improve GMP as a whole. After 30 years, I can't just let go and I’m sure I’ll be following developments for some time to come. I can’t wait to see what topics will be on the horizon next.