GAMP’s Biggest Problem is the Name

GAMP5 is pretty clear in its ambition:

This Guide applies to computerized systems used in regulated activities covered by:

•Good Manufacturing Practice (GMP) (pharmaceutical, including Active Pharmaceutical Ingredient (API), veterinary, and blood)

•Good Clinical Practice (GCP)

•Good Laboratory Practice (GLP)•Good Distribution Practice (GDP)

•Good Pharmacovigilance Practices (GVP)

•Medical Device Regulations (where applicable and appropriate, e.g., for systems used as part of production or the quality system, and for some examples of Software as a Medical Device (SaMD1))
GAMP 5: A Risk-Based Approach to Compliant GxP Computerized Systems (2nd edition),

The biggest problem with GAMP is when you search GAMP you get:

That’s right, the ISPE telling you that GAMP is all about manufacturing. A point that Wikipedia is more than happy to reinforce: https://en.wikipedia.org/wiki/Good_automated_manufacturing_practice

This means that I spend a lot of time explaining why GAMP is relevant outside of manufacturing, to a lot of skeptical people who already struggle with the idea that GCP or GLP isn’t some special and unique flower.

To add to that, it is structured like a GxP. I see a G-some letters-P I instantly think Good <something> Practices. It is how my brain and the brain of every single person who works in the GxPs have been trained.

Second, what is that 5? What does it mean? It’s such a bit of esoteric lore that I have to spend more time explaining. For absolutely no value.

And then last, I inevitably have to deal with skepticism about something published by the International Society of Pharmaceutical Engineering being even remotely relevant to the work a study investigator is doing.

Without a doubt, GAMP is a powerful methodology and toolbox. It just shoots itself in the foot every time. It is unfortunate that with the 2nd edition the ISPE did not take a big breath and successfully rebrand as maybe GDIP or something.

Thoughts on ISPE 2022 Aseptic Conference

Just finished up the 2022 ISPE Aseptic Conference, and here are a few thoughts.

EU GMP Annex 1 expected in later half of the year

Paul Gustafson, chair of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) and a senior corporate regulatory compliance and enforcement advisor with Health Canada, stated that the plan was to issue the widely anticipated Annex 1 in mid-year 2022. He repeatedly said July to September so that is interesting news and start getting your contamination control strategies going. There will be a one-year period before in force, with 2 years on some of the lyophilizer requirements.

For those keeping track, it retains the provision calling for testing filters used in the sterilization process, pre-use, post-sterilization integrity testing (PUPSIT). The PUPSIT provision “has driven a substantial amount of discussion and has resulted in a number of papers being drafted,” said Gustafson. This was a very gracious understatement, and I have to admit I really admired his Canadian humor.

FDA continues to evaluate COVID inspection measures

Alonza Cruse, Director of the Office of Pharmaceutical Quality Operations at FDA/ORA did a thorough job going through the COVID measures of Remote Regulatory Assessments and Remote Interactive Evaluations and discussed how the agency was in the process of learning how best to do things going forward.

He also clearly state how they were continuing to get back to normal inspections and discussed new personnel in foreign offices, such as India.

Highlights from Panels

One of my favorite panels was Jo Ann Jacobs and Kara Vogt speaking on “Building Resiliency into Single-Use-Technology Systems” They laid out some good work they are doing as part of a startup to design good functional equivalency and supplier management, obviously learning from PPAP and similar measures. Quite well done. While it leans heavily into my own practice around functional equivalency it was good to see such a rock-solid implementation, and I felt like I learned a few good ideas.

I spoke on Contamination Control, Risk Management and the Quality Management System, having a blast doing so. I was followed by Christa Myers who spoke on “Contamination Control Strategy: From Annex 1 Draft Requirements to Implementation in Practice.” We made a good duo and between the two I hope participants got a real solid idea on how to do this contamination control strategy effectively.

I learned a lot about robotics and isolators.

Still a big fan of ISPE’s Women in Pharma.

Driving towards a Culture of Excellence

What do we mean when we discuss culture, which is sort of an all-encompassing word that seems difficult to pin down, or can be a rather nebulous way to refer to something bigger than any one individual or team.

Many definitions are available to describe culture. Formally, culture can be defined as “the [predominant] beliefs, values, attitudes, behaviors, and practices that are characteristic of a group of people” (Warrick, 2015). Culture can usually be described as the symbols, power structures, organisational structures, control systems, rituals & routines, and stories of a group.

Johnson & Scholes Cultural Web (this illustration: www.businessgrowthhub.com)

Why does culture matter, well for starts let’s look at some differences between high and low performing cultures.

High Performance Cultures	Low Performance Cultures
Leaders are skilled, admired, and build organizations that excel at results and at taking excellent care of their people and their customers	Leaders provide minimal leadership, are not trusted and admired, and do little to engage and involve their people
Clear and compelling vision, mission, goals, and strategy	Vision, mission, goals, and strategy are unclear, not compelling, not used, or do not exist
Core values drive the culture and are used in decision making	Core values are unclear, not compelling, not used, or do not exist
Committed to excellence, ethics, and doing things right	Lack of commitment to excellence, questionable ethics, and a reputation for doing what is expedient rather than what is right
Clear roles, responsibilities, and success criteria, and strong commitment to engaging, empowering, and developing people	Unclear roles and responsibilities and little interest in fully utilizing and developing the capabilities and potential of people
Positive, can-do work environment	Negative, tense, stressful, and/or resistant work environment
Open, candid, straightforward, and transparent communication	Guarded communication, reluctance to be open and straightforward, and consequences for saying things leaders do not want to hear
Teamwork, collaboration, and involvement are the norm	Top-down decision making with minimal teamwork, collaboration, and involvement
Emphasis on constant improvement and state-of-the-art knowledge and practices	Slow to make needed improvements and behind times in knowledge and practices
Willingness to change, adapt, learn from successes and mistakes, take reasonable risk, and try new things	Poorly planned change, resistance to change, minimal learning from successes and mistakes, and either risk averse or risk foolish

Culture can either be built in a purposeful way or left to chance. As we strive for excellence we need to be methodical about building and sustaining cultures we want to drive excellence. A few guidelines then:

Make strategy and culture important leadership priorities
Develop a clear understanding of the present culture
Identify, communicate, educate, and engage employees in the cultural ideals
Role model desired behaviors
Recruit and develop for culture
Align for consistency between strategy and culture
Recognize and reward desired behaviors and practices
Use symbols, ceremonies, socialization, and stories to reinforce culture
Appoint a culture team
Monitor and manage the culture

What most of struggle with is how to actually do that. Of the many papers and articles I’ve read on the subject, my favorite might be from the International Society of Pharmaceutical engineers (ISPE).

The ISPE in 2015 introduced a cultural excellence framework which was expanded on in their 2017 Cultural Excellence Report. I’ve returned to this report again and again and continue to mine it for ideas for continual improvement and change in my organization.

ISPE’s Six dimensions of cultural excellence framework

The six dimensions to build and maintain cultural excellence are:

Leadership and vision: Leaders establish and engender the vision for the organization. Their thoughts, words, and actions about quality are critical in establishing and maintaining a culture of operational excellence. Leadership and vision, therefore, play a key role in establishing the culture, either within a local manufacturing site or across the company.
Mindset and attitudes: These play a key role in driving cultural performance, although they can be difficult to define, observe, and measure. Leaders can assess, monitor, and develop the desired cultural excellence mindset and attitudes within their organizations, using the practical and powerful approaches outlined in this report.
Gemba walks: Management engagement on the floor is a powerful way to demonstrate quality commitment to all members of the organization. Gemba walks allow site leaders to communicate clear messages using open and honest dialogue, and provide a real indication of progress toward desired behaviors at all levels. Gemba walks also empower front-line employees by recognizing their contributions to site results and involving them in problem-solving and continuous improvement.
Leading quality indicators and triggers: There are inherent links between culture,
behavior, and leading quality indicators (LQIs) that drive desired patient-focused
behaviors. Monitoring and surveillance of key triggers and the design of LQIs are highly recommended practices to help shape cultural excellence.
Oversight and review: Management oversight and review practices that engage both management and employees support a healthy quality culture because they demonstrate transparency, facilitate dialogue, bring attention to issues so they can be addressed, and highlight best practices so they can be replicated.
Structural enablers: These support the desired behaviors, help speed the pace of change, and improve performance over time. They include:
–– Develop a learning organization
–– Establish learning teams
–– Influence and recognize organizational change
–– Solve problems proactively
–– Identify true root cause

Sources

R.D. Day. Leading and Managing People in the Dynamic Organization. Psychology Press, London, UK (2014)
ISPE. Cultural Excellence Report. ISPE, Bethesda (2017)
R.N. Lussier, C.F. Achua. Leadership: Theory, application, and skill development (6th ed.), Cengage Learning, Boston (2016)
D.D. Warrick, J. Mueller (Eds.), Lessons in changing cultures: Learning from real world cases, RossiSmith Academic Publishing, Oxford, UK (2015)