Karen Ginsbury’s Quality Blog #1: Welcome 2020

2020 Vision

Welcome 2020 – Happy New Year and Happy Decade

Welcome also, to my first ever blog.  I plan to share thoughts and ramblings from time to time – my happy and grumpy cats, to use a term many of you readers have heard from me in the past.


20/20 vision, according to the American Optometric Association, is a term used to express normal visual acuity – clarity or sharpness of vision.  Having 20/20 vision does not necessarily mean you have perfect vision. Thinking about the PQS – Pharmaceutical Quality System, I wonder if we have visual acuity about that.  

Two questions:

  1. Why Pharmaceutical and not just “Quality System?”
  2. How close is your system to perfection?

A new year and a new decade is a time for reflection: we should look back, appreciate our successes, understand our failures and plan the future.  To tell the truth, I can’t really remember much about 2010 – I was in my forties in the full swing of work and just “did stuff.” I am not sure that I planned much – it just kind of happened.  

Now let’s think about the two questions in the context of 2020, visual acuity, reflection and forward planning.  At the end, let’s see if we can consider some visual acuity in a 2020 vision for our Quality Systems.

Question #1:  Why “PQS” rather than QS.  Historical I suspect. In the 1960s-1970s (just before my entry to the workforce), the GMPs were first written.  They came, like a traffic light at an intersection after tragedy. After the Elixir of Death in the 1930s (first documented instance of DEG in glycerol?) and thalidomide in the 1960s, it was clear that some specific requirements were needed for manufacturers in the pharma arena.  In the 1970’s and 1980’s we had the Devenport Incident with contaminated infusion fluids killing people and the traffic light that went up was “Validation” which carried us into the 1980’s with FDA’s first Process Validation Guide. We also had our first brush with data integrity, in the Generic Drug Scandal – where competitor tablets were coated a different color and sent to bioequivalence studies, resulting in FDA’s PreApproval Inspection program.  

The 1990’s saw the introduction of computers and the start of globalization.  We got ICH set up and Q1 on Stability and Q2 on methods validation – Huge steps forward for industry and regulator alike in aligning conditions and practices and reducing waste in duplication of effort for different markets in the world.  We also saw 21CFR Part 11 – electronic signatures and records. Let’s not forget the Barr court case, OOS results procedures and FDA’s OOS guidance.  

Anyone remember the fears of Y2K – Year 2000?  Almost none of them materialized. 2006 was a year for investigational drugs with the TeGenero fiasco and also Able Laboratories and their data integrity issues.  We got a ”first in humans guidance” from EMA in response whereas FDA put out their guidance on GMP for Phase 1 which actually exempts (to this day) phase 1 clinical trials material from complying with 21CFR Parts 210, 211 GMPs.  Supposedly it must be manufactured in compliance with GMP to meet the requirements of the FD&C act, but since exempted from 210 and 211, there are actually no GMPs for phase 1 material to comply with – just a guidance which contains non-binding recommendations.

Nothing hotted up more than in 2008 when we had the deliberately contaminated Heparin from China and supply chain became king.  Obama came into power, and appointed Margaret Hamburg commissioner and she was told to enforce, enforce, enforce because of the contaminated peanuts.  (Obama’s daughter was seven and taking peanut butter sandwiches to school). So 483’s and warning letters shot up with “rapid and effective enforcement.”  A USA today article from May 2010 pointed out that 43 warning letters had been issued since the start of the year as opposed to one in the preceding year. Guess what happened next… You got it – drug shortages!! 

Only now, December 2018 has congress required a multi-disciplinary task force chaired by FDA to examine root causes for drug shortages and the report concludes the root causes are:

Root Cause #1 Lack of incentive because market forces make some drugs less profitable.  Refer also to the Economist September article “the Parrots Eat ‘em All” – which mentions the collaboration between Xellia and Civica Rx to ensure supply of essentials antibiotics and other essential generic medications.

Root Cause #2 The market does not recognize and reward manufacturers for mature quality management systems.  Perhaps the most inward-looking observation of the past 60 years, is the following quote from the report:
“All manufacturers must meet regulatory requirements for adherence to CGMPs, which set a minimum threshold that companies must achieve in order to be allowed to supply the US marketplace.  Mature quality management, however, starts with a foundational quality management system that conforms to CGMPS and builds in a performance and patient focus, that utilizes technology, statistical process control, and planning activities to ensure a reliable supply of the drugs manufactured at the facility.”

Remember question 1?  Why “Pharmaceutical” Quality System?  Visual acuity and a vision for 2020: Let’s make sure we have A modern, effective Quality System.  Not ICH, not GMP (although incorporating these requirements), but ISO9001:2015 – the almost perfect (I will get to question 2 before I close) Quality System Guidance.  

        Let’s make a checklist:

  • Context of the Organization (Pharmaceutical, sterile, non-sterile, combination products etc.)
  • Leadership
  • Resources
  • Process driven
  • Planning (Plan-Do-Check-Act PDCA, process mapping and real risk management)
  • Operations
  • Continual improvement – DIGITIZATION, Pharma 4.0, Continuous Manufacturing?

Root Cause #3 Logistical and Regulatory Challenges make it difficult to recover after a supply chain disruption.  The supply chain has been globalized and increased use of contract manufacturers – several of whom have closed their doors after long delayed rigorous inspections.  Entry of new manufacturers, suppliers or new facilities / buildings face high burdens of regulatory acceptance.

Remember Question #2? How close is your system to perfection?  We can all agree that non quality system is perfect – pharmaceutical or other.  Nor should we consider this the desired state or (worse still) believe that our system is perfect.  To do so would forestall continuous improvement and progress. Visual acuity demands of us that we spend a few minutes defining the PURPOSE of a quality system.  Congress has forced FDA to do just that. The conclusions are powerful:

GMPs are NOT a quality system and never were intended to be one.  They are a series of requirements. Philip Crosby in Quality is Free defines quality as “meeting requirements.”  I would dare to go further and say it is “Meeting all the requirements all the time” in which case we must define the requirements.  ISO9001:2015 is an excellent roadmap for setting up an effective system.

FDA root cause #2 needs further investigation – Mature quality management…starts with a foundational quality management system that conforms to CGMPS and builds in a performance and patient focus, that utilizes technology, statistical process control, and planning activities to ensure a reliable supply of the drugs manufactured at the facility.

My next blog will investigate what a foundational quality system is and if CGMP conformance can be integrated and the system still be effective?  It will consider the stumbling blocks which industry AND regulator have, and continue to place in the way of just such a system and ask why other industries, of no less criticality than pharma manage to implement foundational quality systems.

Two teasers and updates:

  1. ICH Q12 was released at the end of November 2019 as step 4 for implementation: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management
  2. Also in November 2019, PIC/s released a draft guidance for their inspectors: How to Evaluate / Demonstrate the Effectiveness of a Pharmaceutical Quality System in relation to Risk-based Change Management

Both of these documents are grumpy cats, and possibly happy cats as well.  Watch this space…

Here’s wishing you a happy, healthy and uplifting 2020, filled with visual acuity.