July, the fifth edition of the PDA/DHI book, GMP in Practice: Regulatory Expectations for the Pharmaceutical Industry was published. The PDA Letter interviewed authors Tim Sandle and James Vesper about this bestselling book, which can be purchased in the PDA Bookstore.
PDA Letter: Why do you think this book
has consistently been a bestseller?
Sandle: There is nothing else out there
that reviews the major GMPs in this
way—breaking GMPs down into the
most important areas, and then comparing the various clauses. This makes the
book a must for those who are regularly
inspected by more than one agency or
wish to operate in different regions.
Without this book, the task anyone must face
in meeting these challenges is enormous.
Vesper: I suspect there are a couple of
reasons. First, in many cases the GMPs are
not all that specific—they give the “what”
and sometimes a high-level “how.” For example, U.S. GMPs, say “adequate space...
does that really mean? By using different
requirements from Canada, the European
WHO and ICH, we can get a
richer understanding of what inspectors
expect to see. Second, with globalization,
we in the industry need to have a certain
amount of harmonization to meet all
applicable requirements. Companies have
been doing that harmonization internally.
This book is aimed at helping with that.
PDA Letter: What is different about this
Sandle: The main difference is that all
the GMPs have been updated. There have
been some changes to U.S. GMPs due to
new U.S. FDA guidances, a vast number
of European GMP chapters have been
rewritten and Canadian regulations have
been completely revamped. In addition,
the major regulatory agencies have adopted the ICH quality guidelines.
Putting all this together, it is clear that the
scope of GMP continues to grow. This
can be seen with GDP, which has become
far more detailed in relation to the supply
chain and with data integrity. Each major
regulatory agency has issued guidance for the latter. A further change since the last
edition has been the expansion in single-
use, disposable technology, which brings
with it areas to consider like leachables,
extractables and methods of sterilization.
The book also highlights the potential applicability of Annex 1 to nonsterile manufacturing, and there are elements here that
can be applied, such as personnel controls,
disinfection and training.
Vesper: I suspect there are a couple of
reasons. The EU GMPs have been updated since the 4th edition came out in 2011,
so this new edition reflects these changes.
We were all ready to send the manuscript
to the printer when the Canadians finalized their revised GMPs that take effect in
October of this year, so we went back and
revised/updated those references. Because
of the global concern for data quality and
data integrity, we thought that deserved a
dedicated chapter. Annex 1 was not finalized when we were writing this; we had
to rely on the draft issued in December
more from a conceptual standpoint.
PDA Letter: What are some of the
common expectations that you
have seen for elements included in a
pharmaceutical quality system?
Sandle: The big push across the GMPs
with pharmaceutical quality systems lies
in the need for a holistic strategy, in that
each of the various elements required
for a robust quality system needs to be
joined together into a coherent whole.
Structuring an internal company document around the different chapters in this
book would provide a useful framework
for companies that lack such a document.
This is also important because a company’s pharmaceutical quality system will
be evaluated during an inspection, and it
plays an important role in the new drug
product submission process.
Vesper: Some of the “themes” or common threads that I see running through
the pharmaceutical quality system include
not just risk management but risk-based
thinking. To me, this means not just doing formal risk assessments but viewing all
that we do in terms of understanding risks
and taking appropriate actions to reduce
those risks that we know to be significant.
Also, looking at trends—what are the data
telling us and how should we respond?
Management support is a third theme—
understanding what the issues really are
and taking proactive steps to resolve them.
PDA Letter: Does this book address
new technologies and processes, such
as parametric release?
Sandle: The book contains all of the
guidance on parametric release, which is
linked to the chapter on terminal sterilization.
We recognize that parametric release
is of interest to a number of firms, in
terms of saving time on batch releases and
with resources. There are other benefits as
well, like manufacturing flexibility (moving product to market more rapidly where there are drug shortages), gaining better process understanding and strengthening manufacturing controls.
Parametric release also features in the parts of the book applicable to nonsterile manufacturing, such as the use of scientifically sound in-
process controls and chemical measurements.
PDA Letter: Who would be best served by reading this book?
Sandle: The audience is anyone involved with pharmaceuticals and healthcare products, for there is no area untouched by GMP—from
purchasing to distribution of medicines. The substantive sections of the book, which are about manufacturing, laboratory testing and release,
will appeal to quality assurance, quality control, validation, manufacturing and inspection departments. This enables companies to benchmark their practices.
The book is also useful when preparing for
international inspections, especially if the
company is unfamiliar with the regulators who will be conducting the audit. So,
those in the United States who are unfamiliar with inspectorates following EMA
GMPs can get a feel for what is required
and, likewise, will those in Europe can
better prepare for a U.S. FDA inspection.
Vesper: From what people have told us
about previous editions, it has been used
as a reference by those in quality assurance
and also technical/manufacturing operations. One quality assurance person said it
was valuable to have expectations covering a certain topic pulled together in one
reference. Another firm used it to train
supervisors, asking them how GMP expectations were realized in their operations
and what needed to be improved.
It will also help readers have much more
fascinating conversations at dinner parties.
About the Experts
Tim Sandle, PhD, is a pharmaceutical
microbiologist with 25 years of experience
working in the pharmaceutical and
James Vesper, PhD, has worked in the
pharma/biopharma industry for more
than 35 years, starting out at Eli Lilly and
Company where his last role was leading
the GMP Training and Education group.