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PET
Radiopharmaceutical
Business
An Insider‘s View
AndreaPecorale
MariaCarmelaInzerillo
PieroA.Salvadori
PET Radiopharmaceutical Business
AndreaPecorale • MariaCarmelaInzerillo
PieroA.Salvadori
PET Radiopharmaceutical
Business
An Insider’s View
ISBN 978-3-031-51907-9 ISBN 978-3-031-51908-6 (eBook)
https://doi.org/10.1007/978-3-031-51908-6
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
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Paper in this product is recyclable.
AndreaPecorale
PET Manufacturing
GE Healthcare
Crescentino, Italy
PieroA.Salvadori
CNR Institute of Clinical Physiology
Pisa, Pisa, Italy
MariaCarmelaInzerillo
Quality Assurance
GE Healthcare
CHIERI, Italy
Tell me and I will forget, show me and I may
remember, involve me and I will understand.
Kong Fuzi (Confucius)
https://t.me/medicina_free
vii
Preface
Following the publication of the rst volume Essence of the PET Radiopharmaceutical
Business: A Practical Guide, many colleagues and friends asked me whether it was
my intention to write a second book in the future; my answer was afrmative.
There were some points in the previous volume whose development did not fully
satisfy me.
The rst was related to how great operational results can still be achieved, despite
the small organizational dimensions of a PET production site.
In this topic, I think that an overview of the differences between the much larger
and more organized SPECT radiopharmaceutical manufacturing sites and the PET
sites could help the reader to perceive the technical and organizational elements that
characterize a PET site and that are the basis of its activities.
The SPECT facility I describe is where I had the opportunity to work in the
1990s and that in some way provided me with a great and useful experience before
I started the PET production project, which began in 2001 and still continues to be
fully operative nowadays.
It was a professional, but rst of all a human experience, without which I would
have hardly been able to set up the next challenge with PET tracers and the short-
lived uorine-18 as a radionuclide.
The industrial culture that I have learned over many years of SPECT manufactur-
ing activity, combined with the awareness of the implications of radioactive risk,
much higher than in PET radiopharmacy, matured the technical knowledge that
allowed me to face the next challenges with sufcient and reasonable condence.
In the SPECT business, all the technical and radioprotection challenges were, in
fact, so impactful and requiring such a detailed analysis, that even the slightest
operational changes involved months of studies and feasibility tests.
I was privileged in this; I must admit.
Many if not all the SPECT productions programs I worked on at the beginning of
my career no longer exist, at least in Italy, and manufacturing facilities have concen-
trated in fewer locations; however, a large portion of Nuclear Medicine diagnostics
still remains hinged on SPECT products. Younger colleagues, who face the world of
radiopharmaceuticals today, mostly focused on PET, may not feel the wonder we
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viii
received listening to legends, like that talking about the operator who was “able to
light a match remotely by using the tele-manipulator system of a ve-meter-high,
heavily shielded hot-cell.”
I would suggest to those who intend to enter the world of PET radiopharmaceu-
ticals to spend rst a few months in a SPECT facility; it would be useful to get
experience and understand the business philosophy by living in the world where “it
all began” and develop the specic mindset needed to face all the operational chal-
lenges and their connected radioprotection aspects.
PET market is also very variable, particularly in the context of its organizational
aspects; therefore, I felt useful to make a comparison between my PET operational
experience in Italy and other European situations, in which I was involved over the
time. A picture emerges in which the temptation to operate with the logic of the
“silos” (unwillingness to share information or knowledge across different depart-
ments), always present at all levels, has fewer chance of success in PET radiophar-
maceutical production than other conventional pharmaceutical frameworks.
One aspect, that is particularly signicant in my opinion, recalls the “problem of
the spider in the hole”: how to get it out! That is exactly what critical issue occurs
in PET: the need to “pulling out” the production department from its comfort zone
and oblige the operators to an open and continuous confrontation with all the other
functions, like distribution and commercial departments, not directly involved in the
preparation of products.
Of course, I may have expressed a limited vision on this last point, the one based
exclusively on the “operational” perspective of a production manager.
The second aspect that, in my opinion, deserved an in-depth analysis is the devel-
opment of the collaboration with third-party companies that act as contract manu-
facturing organizations (CMO).
In any business, the innovation and evolution of products remain central.
Regarding the development of new tracers, I tried to focus my analysis on the rela-
tionship between Research and Development (R&D) and the commercial world as
well as the operational mechanisms that should guide the company functions in the
choice of new radiotracers.
I thought it would have been useful for the reader to see what, of course in my
view, are the main differences between “new,” “mature,” and “still developing” trac-
ers: elements that I tried to summarize also in a comparative table.
Two “evergreen” aspects, further integrated with respect to the rst book, are
included in the analysis: order management and production reliability. On these
points, I included examples of classications to promote the logic of comparison
and the analysis of results, especially in the context of production networks that
include several CMOs.
In the second chapter, I explored the subject of production projects conducted in
collaboration with nonindustrial partners, including Academia. This subject is very
close to me because it was the frame of the construction of the rst PET tracer
manufacturing site that I developed directly.
Preface
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ix
During my professional activity, I have experienced the acquisition from another
company of the PET site I managed. Despite the shocking situation, I think that it
was a useful experience and an opportunity for me to learn how to explain and
report, in this kind of a situation, the peculiar technical/regulatory aspects applica-
ble to PET products. In fact, there is no specic literature regarding PET sites that
can help both parties, the buyer and who is acquired on the evaluation of the main
aspects to be taken into consideration as well as the connected risks, including the
economic ones.
Finally, the PET warehouse chapter: a personal tribute to the small world of PET
tracers, often little known, in which night shift work is conducted, and one never
knows what may happen.
I think it would be interesting for the reader to have PET views different from
what I was able to offer, which was limited fundamentally to the production part in
an industrial environment. I therefore involved in the project of this book two col-
leagues and friends, Maria Carmela and Piero. We have come a long way of work-
ing together and shared, each from our side, the adventure of PET tracer
manufacturing.
Crescentino, Italy AndreaPecorale
Preface
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xi
Preface
When Andrea contacted me to discuss my possible interest in participating in the
drafting of a chapter on PET Quality Assurance (QA), I initially had some concerns.
In fact, for about a couple of years after my retirement, I spent my time doing my
best to recover my personal life, and I had only few occasional participations to the
activity of a pharmaceutical association.
However, the proposal was interesting to me, and, in the end, I agreed to collabo-
rate, even with a special focus.
I found particularly stimulating both the opportunity, even personal, to carry out
a critical and structured analysis with my experience in the QA for PET sites, as
well as the hope of providing colleagues, and those who approach the QA world,
with some indications, based on real experiences. Hopefully, it could provide the
reader with practical methods and consideration which are applicable to routine,
everyday activities, taking however for granted the knowledge of applicable phar-
maceutical regulation.
It is a sort of summary of what QA has been for me, not just in the PET eld, and
a reection on the most frequent mistakes we experimented, that it would be better
to know in advance not to repeat them.
To simplify reading, I proposed to use in the chapter the format of an interview,
containing a series of specic questions raised on the basis of the curiosity of a
representing member of the production team (Andrea). I found interesting that the
interview began asking why I chose working in QA and what personality traits are
needed in this environment to work effectively and to survive.
Moreover, I added some practical descriptions of the methods I have adopted to
recruit and develop the skills of QA personnel in my team, and in the teams of third-
party sites as well.
To answer Andrea’s questions on some specic aspects of the Quality System
(QS), I have provided some general information about procedures, deviations,
audits, complaints, and Key Performance Indicators (KPIs). However, I always
aimed at a very practical approach, putting to evidence the aspects that I personally
experienced, sometimes with unpleasant emotions and sometimes with fun.
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xii
Finally, Andrea and I wanted to make together an overview on the aspects that
should be focused when checking whether the QS under evaluation during an audit
is a real one or it is a movie broadcast only for auditors. It looks like a joke, but if
one thinks applying QS requirements only temporarily and not continuously, hop-
ing to save money or simply because the risk was underestimated, the future can
turn very expensive and, in particular, not convenient for the company.
I hope the reader appreciates this part as a simple reection, looking backwards
after some time, on a project of construction of a QS, which was developed through
gradual attempts, but at the same time had to lead to real effective results, such as
production robustness and sale. This reection led us to conclude that, despite all
the difculties, we had done a good job.
Chieri, Italy MariaCarmelaInzerillo
Preface
https://t.me/medicina_free
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