Pharmaceutical Quality Systems

By Neil J. Wilkinson, NSF-DBA | November 9, 2012

ICH Q10 standard ushers in a new era of quality culture

So you think the issue of the ICH Q10 Pharmaceutical Quality System standard was merely an academic exercise, one that will have no impact on the way your firm does business in the future? If so, you had better read this article! ICH Q10, finalized in 2008, is well into its implementation journey within the pharmaceutical industry and its practices are now becoming a firm expectation of regulatory agencies around the world.

ICH Q10 had a very long and sometimes difficult conception period. It is important to understand this history to fully understand why ICH Q10 was written and what it means for pharmaceutical quality systems.

The roots of Q10 can be traced back to discussions between industry and the FDA in the early 2000s. The 1990s had seen the impact of the “generics scandal” and as a result, trust had been lost between the FDA and the entire pharma industry (instead of the few companies that were not compliant). This led to a culture of what has since became known as “blind compliance,” where companies were not comfortable questioning FDA policies and guidelines.

Pushed by certain FDA investigators at the time, the FDA began to represent “Fear, Depression, and Anxiety” to firms, including those who still worked to be science- and patient-based. The situation appeared to be a gridlock, with no one benefiting. In the early 2000s, a group of industry leaders engaged on behalf of the Pharmaceutical Research and Manufacturers of America (PhRMA) trade association began discussions with the FDA to learn where the problems were in the industry, and with the FDA’s regulatory processes and compliance in focus, to seek a way forward.

In 2001, an independent survey by PricewaterhouseCoopers (PwC) on the state of pharma manufacturing confirmed what many of us in the industry already knew: We were way behind other sectors in manufacturing and quality, didn’t understand our products and processes well enough, and generated massive levels of waste, rejects and reworks. However, products released to the market were believed to be fit for purpose as a result of the large amounts of inspection, testing, reworking and rejections undertaken. ”Quality by design” was a distant dream then.

Compared to other industry sectors, the pharma industry was a dinosaur, decades behind in terms of a quality culture and mindset. (It still is!) We had failed to take on board then the ideas and concepts that had led to massive and continuous improvements in the automobile, electronics, chemical and other sectors over the years.

Why? Because margins were good for many, we were not facing the same direct customer competition seen in other sectors and, after all, “We are the pharmaceutical industry, are regulated, and have Good Manufacturing Practices (GMPs), so these things don’t apply to us.” I have heard those words so many times!

This ignorance, alongside a failure to measure the real costs of quality in our sector — an ideal that even today many firms don’t measure — has also led to a fundamental lack of understanding of the value of quality at senior levels in the pharma sector.

The legal requirement for an ‘Independent Quality Unit’ has also driven some inappropriate ‘us and them’ behaviors, and in few firms had the key quality message been explained to senior leaders in a language they understand – money! In other industries, continual improvement, quality and operational excellence are all thought of as one philosophy.

Headlines such as, The Pharmaceutical industry has a little secret: Even as it invents new drugs its manufacturing techniques lag far behind those of potato chip and laundry soap makers, (Wall Street Journal, 2003) and a further damning report by IBM in 2005, The Metamorphosis of Manufacturing, continued to hit us hard. Sadly, the claims were largely justified.

Industry and FDA discussions continued and in 2002 the FDA’s cGMPs for the 21st Century report was released. This important, groundbreaking report defined the change in FDA’s philosophy. It contains much of the thinking that has percolated down from FDA senior leaders since then, and it remains relevant today. Full credit is given to the FDA for its leadership and for listening to the Industry about the problems it faced. Clearly, both parties had contributed to the status quo at the time, but importantly both saw a need to move forward for the benefit of all parties, including the patient, taking a queue from some of the quality manufacturing concepts used in other industry sectors. W. Edwards Deming was over 50 years ago!

At this time in the early 2000s, I chaired the European Federation of Pharmaceutical Industries and Associations’ (EFPIA) manufacturing technical group. As globalization was now accelerating dramatically, industry trade groups met and decided that if things were to change for the better, these initiatives needed to be accepted and implemented on a global basis — a view not fully understood, or shared, at the time by all regulatory agencies.

The resulting discussions lead to input at the ICH level in 2003, and an ICH quality vision was agreed upon: “To create a single, harmonized global quality standard and interpretation based on good science and risk management principles.” The ICH process is the only forum where regulators and industry meet on the same terms to craft a product, the ICH guidelines. Further discussions led to the evolution of the ICH Q8/9/10 trio, and the subsequent issue of the three ICH guidelines. Remember that ICH Q8/9/10 were conceived together and should be integrated together under the umbrella of a firm’s pharmaceutical quality system (PQS).

ICH Q10 Key Components
The ICH Q10 document was produced by a team which borrowed from other international quality management standards and concepts that existed in other sectors, most notably the ISO Quality Management System’s ISO 9001 series. The GMPs are a legal requirement, but now form a part of ICH Q10 requirements as well.

Q10 adds the critical component of management responsibility, for both in-sourced and outsourced activities. It also introduces the lifecycle approach concept where the PQS is applied throughout the product lifecycle. It builds in the concepts of integrating quality risk management (Q9) and knowledge management throughout, to enable the PQS processes. Q10 drives continual improvements of products and processes, as well as the PQS itself.

These key concepts go way beyond the previous GMPs and the way the GMPs were interpreted. Just following the GMPs and passing occasional regulatory inspections will now become an even more dangerous strategy, as GMPs alone have never driven continued improvement of products, processes and the PQS itself in the way ICH Q10 intends to.

The Implementation Journey And the Regulators’ Views
Quite simply, adoption of an ICH Q10 pharmaceutical quality system makes good business sense by reducing risk, as confirmed by those firms that have embarked on the implementation journey. But there are still many firms that will dig a hole in the sand and wait for the FDA to tell them to implement ICH Q10 PQS. Some will still roll the dice, but these are usually the firms that often later end up paying hundreds of millions of dollars in remediation due to regulatory enforcement activities.

The FDA published ICH Q10 as FDA guidance, which indicates that this represents the agency’s current thinking and expectations for quality systems. Speakers from FDA and European Medicines Association (EMA) have told industry at many recent public conferences that they are expected to now follow an ICH Q10 model. Regulators can hardly do more to publicize their support for ICH Q10.

Key implementation strategies from firms include:
  • ICH Q10 must have top-level, cross-functional support and an agreed business case to obtain senior management support.
  • Make the financial case by showing how ICH Q10 can save money and reduce risks to gain senior management support.
  • It cannot be driven by the quality unit alone.
  • Simple gap analysis and process mapping tools help.
  • It helps to prioritize and start small to “break down the elephant.”
  • Don’t wait for the FDA to find you out – it is too late!
  • ICH Q10 is not just the latest fad; it represents a cultural change to the way the pharma sector needs to operate to move toward a better state.
  • Cultural changes do not happen overnight.
  • Training and education programs for quality professionals (not just quality unit staff) need to evolve to explain the “WHY,” not just the “HOW.”
  • To achieve success, both industry and regulators need to continue to open their minds to affect this positive change.
  • Compliance should be simply a deliverable from the PQS, not a separate industry.
  • Pharma needs to be less inward looking and stop thinking in terms of:
                o “We are the pharma sector; this does not apply to us.”
                o “The regulators would never let this happen.”
  • Individuals with competencies from other areas are needed:
                o Statisticians
                o Operational Excellence (OPEX) experts
                o Quality professionals
  • Companies should not embark on LEAN quality management initiatives until first understanding their processes.
  • The evolution continues:
                o 1970s – 80s: QC mentality
                o 1980s – 2000s: QA mentality
                o 2000s – 2020?: PQS mentality
                o 2020?: Operation excellence is part of quality mentality?

Together we can implement these quality management systems, to reduce risk, improve regulatory relationships and to create higher quality pharmaceuticals that protect and improve human health. 

Neil J. Wilkinson is currently the senior partner at NSF-DBA’s Boston office, which is part of the Health Sciences division of the global public health and safety organization, NSF International. He acted as the EU Topic Leader for the ICH Expert Work Group that produced the ICH Q10 Pharmaceutical Quality System guideline. Mr. Wilkinson can be reached at njw@nsf-dba.com for advice on NSF-DBA training, auditing and consulting services.