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C o m m e n ta r y
Cleaning –
Where Are We Now And
Where Are We Headed With
Important Concept?
S P E A K E R : D R . B I L L H A L L • C O M P I L E D B Y J U A N I TA F U G E
❖
Dr. Bill Hall, long time collaborator of IVT, international cleaning expert, mentor, and much honored contributor to FDA-regulated industry, was the Keynote Speaker at the IVT Cleaning Validation and Critical
Cleaning Processes conference held in Chicago July 24 through 27. Because Doctor Hall is celebrating
his 50th year of service as an active practitioner within Industry, he chose to illustrate the importance of
cleaning concerns by highlighting their impact over the years. He looked at the past, present, and future
of the important concept of pharmaceutical cleaning.
HISTORICAL PERSPECTIVE
Why are we engaged in work with drugs, the double
edged sword that can bring us improved health, but can
also hurt us? Dr. Hall's answer- among so many other options - is that in doing so, we improve the quality of life
for so many and we provide a better life for our children.
To discover where we are going, Bill chose to look
first at where we have been. “I believe that you have to
look back before you can move forward,” he said. He
started with the beginning of the FDA (1906) and a quote
from the book that started it all, The Jungle, by Upton
Sinclair:
“It was too dark in these storage places
to see well, but a man could run his
hand over these piles of meat and sweep
off handfuls of the dried dung of rats.
These rats were nuisances, and the packers would put poisoned bread out for
them, they would die, and then rats,
bread, and meat would go into the
sausage hoppers together.”
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This passage graphically illustrates the state of our
food supply at the turn of the last century and contrasts
the tremendous progress made over the past decades in
application and enforcement of high quality standards
within the food industry since that time.
Unfortunately a number of examples of past
tragedies exist but serve to point to our progress as well.
The first major problem the FDA and the nation faced together was to contend with the elixir of sulfanilamide ethylene glycol - contamination which caused 107 fatalities. It was this tragedy that brought about a revision to
the 1906 drug law and ushered in the Federal Food,
Drug, and Cosmetic Act of 1938 that is the basis of our
modern regulations.1
The thalidomide tragedy followed in the 1960's when
the drug was used as a sleep aid and was released to the
market in Europe, but not the U.S. (due to efforts of Dr.
Frances Kelsey, FDA). Unfortunately, some pregnant
women traveling in Europe were given the drug with devastating affect to their babies.2
Thalidomide was finally approved in 1998 in the U.S.
but for certain specific conditions and not for pregnant
women.
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Another tragedy from the past included the pesticide
contamination of actives sent to Europe for micronization. An active was stored in bulk containers (fiber drums)
that had previously contained pesticides. Many people
died.
A similar event occurred in Virginia several years ago.
The pesticide, kepone, was manufactured in a plant in
Virginia where workers were required to launder their
own uniforms. Kepone transferred in the washing machine to families’ clothes (especially children). The kepone was absorbed through the skin and caused injury to
family members.
OUR PRESENT SITUATION
Does this mean all tragedies are limited to the past?
Not at all! Within the food industry we have experienced
recent situations with:
• Spinach
• Lettuce
• Shellfish
• Various e.coli contaminations
• Bovine encephalitis (“mad cow” disease)
• Viruses in the blood bank
Recently (5/5/07) a congressmen stated on a TV talk
show that the FDA should be doubled in size.
The recent ethylene glycol situation wherein ethylene
glycol was substituted for glycerin in cough syrup is actually a counterfeiting, substitution, or fraud issue - ethylene glycol is much cheaper than glycerin. A similar event
in Panama last year (2006)3 caused 365 deaths (100 have
been confirmed; the rest await confirmation upon exhumation of the bodies before further decomposition.)
The material originated in China and passed through
three companies on three different continents. None of
the companies tested the syrup to confirm that it was
glycerin. Shipping documentation and labels were altered
and falsely attested to regarding the purity of the material
and the name of the manufacturer. Thus, traders bought
the syrup not knowing where it came from or who manufactured it.
Newspapers say:
“Beyond Panama and China, toxic syrup
has caused poisonings in Haiti,
Bangladesh, Argentina, Nigeria, and
twice in India. In Bangladesh, investigators found poison in seven brands of fever
medication in 1992, but only after countless children died.”
In another issue in which China has been related –
The Melamine Incident:
“China is also being accused by U.S. authorities of exporting wheat gluten with
an industrial chemical, melamine, that
ended up in pet food and animal feed.”
This has been confirmed as the cause of death of hundreds, and probably thousands, of pets and animals.
Cleaning versus Containment
In each of these incidents cleaning can be seen as a
major factor. Cleaning is a greater issue than containment. It concerns healthcare personnel (nurses, doctors,
and pharmacists) in hospitals, oncology clinics, etc. Cytotoxic drugs have been found in urine specimens and absorption may be through the skin, lungs, or orally.
Significant concentrations of drugs were found on the
outside of vials (injectables), in some of these cases.
These are alarming danger signals that empahsize the importance of what we do.
SUMMARY
• Cleaning is related to contamination, containment, counterfeiting, etc.
• Mix-ups and outright fraud are continuing, even
today, with the results that the health of the world
is being affected.
• This is one of the important issues in the U.S. and
other countries becoming truly global economies.
M a y 2 0 0 7 • Vo l u m e 1 3 , N u m b e r 3
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SO, WHAT DOES THE FUTURE
LOOK LIKE?
Look for more of the same. There will be more complex relationships of between manufacturing and distribution systems. There will be more control of critical
components within the “quality equation.” That will bring
more opportunity for success or failure; “the peaks will
be higher and the valleys will be lower.” Opportunities for
excellence will be ever-present! ❏
REFERENCES
1. Janssen, W.F., “The U.S. Food and Drug Law: How it
Came, How It Works,” FDC Control, American Society
for Quality Control, Nov. 1988.
2. Grigg, Wm., “The Thalidomide Tragedy - 25 Years Ago,”
FDA Consumer, 1987 appearing in Reference Materials GMP Orientation, Abbott Laboratories, July 1997.
3. http://pqasb.pqarchiver.com/washingtonpost/
access/1146077461.html
ABOUT THE SPEAKER
Dr. William E. Hall is considered an international
expert on cleaning in the Pharmaceutical Industry. He has been a contributor and innovator
within Industry of many of the concepts and approaches currently in use in cleaning programs
today. He has also served as mentor and teacher
to many of those responsible for cleaning programs throughout the world.
With more than 45 years experience, Dr. Hall has
consulted for more than 500 companies worldwide since forming his own consulting firm in
1995. Prior to that, he held various positions over
a 22 year career with Glaxo Wellcome, in areas
including Research and Development, Quality Assurance, and Quality Control. Before entering Industry, Bill worked in academia for seven years as
a professor at the University of North Carolina at
Chapel Hill in the School of Pharmacy. Bill earned
his B.S. degree from the University of Arkansas
and his Ph.D. from the University of Wisconsin at
Madison.
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Bill is a highly respected member of the JVT Editorial Advisory Board, having been inducted into
the IVT Validation Hall of Fame. He has given
hundreds of presentations on the subjects of
process validation, cleaning validation, quality assurance and compliance, as well as drug abuse.
He also serves as an expert witness for the FDA
in the area of GMP compliance and has taught
FDA inspectors in the evaluation of cleaning programs. Dr. Hall can be reached by email at [email protected] or by phone at 910-458-1087.