Karen Ginsbury’s Quality Blog #4 (2021/#1)

June 15, 2021

Prevent # Pharma 4.0 # Digital Maturity

Welcome to… mid 2021… In Israel almost done with the masks. I am on a plane where they are still required as well as in stores in England where I was. I still forget and am SHOCKED when I do. Please remember the next time you write an SOP as a risk mitigating measure and expect it to work based on human behavior… Human beings are not capable of repetitively performing an action correctly over time… and the more complex the action the less capable they are. We need automation to replace humans and eliminate human error…Pharma 4.0, digital maturity.
I really hope you remember from the last blog:
“One of the key purposes of a quality management system is to act as a preventive tool”
Pfizer, Moderna, AstraZeneca, J&J have developed Covid vaccines and all of us are praying they will #PREVENT Covid. Living in Israel I have been privileged to witness a vaccine rollout that was staggeringly well planned and executed. Taking over a sports arena and splitting it between competing Health Fund Organizations, there was ample parking and wheelchair access. Over 2 million vaccines were administered in about three weeks. The vaccination took, from arrival at the facility, 18 minutes – that’s about 30 seconds for registration by identity card number, another 30 seconds until you are ushered into a booth and two minutes for administration of the vaccine. 15 minutes waiting and you are on your way. My mum, my husband and myself completed our second shots by Feb 05th. Some countries had barely started the first shot program in the over 90s.
Below is what I wrote when I started this in March just before my BIG move to new apartment in Jerusalem:
With the mutant strains from England, South Africa, Denmark, Brazil, India… no one can really assure us the vaccine will be 95% effective. Add to that the incredibly complex logistics on the Pfizer vaccine and the complex thawing and dilution scheme, where diluent is not provided with the vial and the multidose vials are giving “more” doses than the label claim… Adds up to lots of questions as to whether it will even come close to the claimed efficacy. Which is not a reason not to take it. But is a reason to wear a mask and socially distance even after taking it. If it is 50% effective, we will be so much better off than now. And maybe I will be proved wrong and it will be 95% effective after all. But for how long?
Happily, I was proved wrong – the numbers in Israel are now close to zero and we no longer need to wear masks INSIDE – this is reason to rejoice. It seems there is herd immunity. Several questions still to be answered: for how long?

My vaccination certificate expires on 05 August 2021 – I think the current plan is to extend it but no one is sure for how long and if and when another shot will be needed. However, I am sure that will be resolved and we are certainly in a far far better place than one year ago.
I want to address some really good points raised by your very own Christina Guldberg at IFF in her email reminding me about this blog (and followed by several more – rather too polite – as this is much overdue – my apologies):
Christina: Our prime minister, Mette Frederiksen, visited Netanyahu to discuss how they could cooperate on vaccine manufacturing… I was thinking “you cannot just manufacture vaccines” – you need to get access to the manufacturing procedures and then you need to either build or qualify a manufacturing plant etc etc. and all this takes time. Also, some companies have offered to change their manufacturing plants into vaccine manufacturing – I wonder what it takes?
Karen: Netanyahu is no longer our Prime Minister! Bennett is an industrialist but has his hands more than full trying to keep together the disparate coalition his colleague Lapid managed to cobble together. Leaving the politics aside, you are SO right. You cannot “just manufacture vaccines.” There is considerable vaccine manufacturing and biopharma know-how in Israel, and I suppose the cooperation would involve knowledge transfer but many many open questions there.
As for building and qualifying a manufacturing plant or changing plants into vaccine manufacturing well… that ties in well with Christina’s next query… and also raises the potential for drug shortages. I mean, if the plants change – who makes whatever they were making previously? That’s how you get a shortage…isn’t it?
Christina: J&J had 15 M vaccines ruined because it was mixed up with AstraZenaca’s vaccine (at a CMO I assume)..I wonder how this could happen?
Karen: The CEO of the company said on live TV that this was NOT a mix-up and was not cross-contamination and that his company discovered the error in QC tests. FDA’s 483, available for download says otherwise – it was the client (presumably J&J) who discovered the mix-up not the CMO – yes it was a contract manufacturing organization. If you read that 483, you will understand that transforming a manufacturing facility or setting one up to produce vaccines at short notice is a TALL ORDER. Pfizer did it – they did it with ONE product in a purpose-built facility using cleanroom pods – modular systems. The CMO took on TWO different vaccines, from two companies, outsourced. They received massive federal funding under a vaccines incentive program and were under huge pressure to produce results / vaccines.
I suspect the reason Pfizer succeeded is because they had in place, a genuine Quality Management System #QMS rather than an ICH Q10 Pharmaceutical Quality System (PQS). This was in place prior to Covid and prior to vaccine manufacture.

QMS = #PREVENT + #PDCA: Plan-Do-Check-Act including or ESPECIALLY when under political scrutiny, political pressure and crazy time-constraints.
PQS = #CAPA + #GMP: Check the boxes (or not – as the 483 shows) or plaster over the non-checked boxes with Corrective Actions when an investigator / inspector points them out.
QMS is holistic and systematic.
PQS is patchwork, piece-meal and ineffective. If you download the 483 with responses for thelaboratory operations (separate from the manufacturing one), you may observe the lack of a full remediation plan. The very serious findings are addressed one by one and the best response is to escalate repeat findings to management review. That is good – but it is still a limited, local solution.

Looking back at my 2020 blogs, my vision for 2020 was to implement P-D-C-A for myself.
Every action that is taken during 2020 and thereafter, will be considered and planned. (P-D-C-A) Implementation will be according to what was planned OR, if what was planned turns out not to be the requirements, then the requirements will be officially changed, people who need to know will be notified and the action will be planned all over again prior to implementation.
As of August 2020, we (my husband and I and my mother) had to move out of our homes (Plan: we sold them and bought in another city), and as our new places weren’t ready, we had to move to a furnished place very kindly lent to us by a fabulous friend. All the careful planning which left several spare months for completion of our project – failed! We did move, but got “stuck” living out of suitcases with 95% of our belongings in storage for seven months. Some of my blogs were written using an ironing board as my office desk. The move to our wonderful new places, happened in March and we are ok and healthy as I hope all of you reading this are too. I couldn’t come to Denmark last year – more Covid fallout. I look forward to coming in August… I also pray that those currently battling Covid, will make it through. Those of us who are healthy are blessed – whatever the restrictions. Let us acknowledge it and in appreciation do a kind deed for a neighbor or friend, or phone someone who lives alone. People are soooo lonely.