UNITED STATES OF AMERICA

FOOD AND DRUG ADMINISTRATION

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CENTER FOR DRUG EVALUATION AND RESEARCH

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USE OF COLOR ON PHARMACEUTICAL PRODUCT

LABELS, LABELING AND PACKAGING

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PUBLIC HEARING

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MONDAY,

MARCH 7, 2005

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The public hearing was held at 8:00 a.m. in the Auditorium of the Lister
Hill Center, Building 38A, National Institutes of Health Campus,
Bethesda, Maryland, Dr. Paul Seligman, presiding.

[PRESENT]{.underline}:

MARY BAKER, Pharm.D. Hospira, Inc.

JAMES BROSELOW Catawba County Medical

Center, Hickory, NC

MICHAEL COHEN Institute for Safe

Medication Practices

JOSEPH CRANSTON American Medical

Association

ALLAN JENSEN, M.D. American Academy of

Ophthalmology

FRANK KYLE American Dental

Association

MARY ANN McELLIGOTT, Ph.D. Novo Nordisk

CHARLES MYERS American Society of

Health Systems

ERIC SHEININ, Ph.D. United States

Pharmacopeia

THOMAS WILLER, Ph.D. Hospira, Inc.

[FDA REPRESENTATIVES]{.underline}:

PAUL SELIGMAN, M.D. Presiding Officer

PETER CARSTENSEN

WILEY CHAMBERS, M.D.

CDR CAROL HOLQUIST, R.Ph.

ROBERT MEYER, M.D.

C-O-N-T-E-N-T-S

Dr. Paul Seligman - Welcome 4

CDR. Carol Holquist - Use of Color on

Pharmaceutical Labeling and

Packaging - an Overview 7

Dr. Charles Myers - American Society of

Health Systems Pharmacists 10

Dr. Thomas Willer - Hospira, Inc. 20

Dr. Mary Baker - Hospira, Inc. 22

Dr. Eric Sheinin - United States Pharmacopeia 37

Dr. Michael R. Cohen - Institute for Safe

Medication Practices 53

Dr. Mary Ann McElligott - Novo Nordisk 107

Dr. Joseph Cranston - American Medical

Association 125

Dr. Frank Kyle - American Dental Association 134

Dr. Allan Jensen - American Academy of

Ophthalmology 142

Dr. James Broselow 153

P-R-O-C-E-E-D-I-N-G-S

8:06 a.m.

DR. SELIGMAN: Good morning. Welcome to the FDA Part 15 hearing on the
use of color on pharmaceutical labeling and packaging.

The objectives of today\'s hearing are to obtain public feedback
regarding the advantages and disadvantages of using color to
differentiate, identify, or classify drug products.

And to hear whether there are specific data to demonstrate whether the
practice works in reducing medication errors or contributes to
medication errors.

And finally to ascertain whether the use of color within certain classes
of drugs improves or is a hindrance to patient safety.

Today we\'re going to have a panel of FDA experts who will be up here at
the front as well as in the front row. And I\'d like to introduce them
briefly and then to talk about the ground rules for today\'s Part 15
hearing.

First of all, the members of the panel are going to be Dr. Robert Meyer,
who is the Director of the Office of Drug Evaluation II in CDER. And
he\'ll be joining us shortly, Dr. Wiley Chambers, who is the Deputy
Director of the Division of Anti-Inflammatory, Analgesic, and
Ophthalmologic Drug Products in CDER, Dr. Peter Carstensen, who is the
Seniors Systems Engineer in the Division of Device Users Programs and
Systems Analysis in the Center for Devices and Radiological Health, CDR.
Carol Holquist, who is the Director of the Division of Medication Errors
of Technical Support in the Center for Drugs, Drug Evaluation, and
Research, and finally myself, Paul Seligman, and I\'m the Director of
the Office of Pharmacoepidemiology and Statistical Science, also in the
Center for Drug Evaluation and Research.

Each speaker will be allocated a specified period of time. FDA panel
members will question each speaker individually after each presentation.
Please keep your talk focused on the hearing questions and limit your
remarks to the time assigned.

The ground rules for a Part 15 hearing include the following:

The hearing is informal. The Rules of Evidence do not apply. No
participant may interrupt the presentation of another participant. Only
the presiding officer, namely myself, and the panel members may question
any person during or at the conclusion of each presentation.

And public hearings under Part 15 are subject to FDA\'s policy and
procedures for electronic media coverage of FDA\'s public administrative
proceedings. Representatives of the electronic media may be permitted,
subject to certain limitations, to videotape, film, or otherwise record
FDA\'s public administrative proceedings, including presentations by the
participants.

Ths meeting will be transcribed and posted on the Internet within 30
days. We will also be accepting written comments to the FDA\'s Division
of Dockets Management until April the 7th.

Finally, as we are guests of the National Library of Medicine\'s Lister
Hill Center, there are a few housekeeping announcements that I want to
make you aware of. First of all, no food or drink or beverages of any
kind are allowed in the auditorium. If you have them at present, please
remove them.

Please set your pagers and cell phones to vibrate.

To activate the audience microphone if you should need it, there\'s a
button in front of the microphone and a red light will come on.

And finally, the message desk phone number here is 301-496-4062 if you
need it.

With that and without \-- if there aren\'t any other questions or issues
related to the beginning of this meeting, I\'d like then to introduce
CDR. Carol Holquist who is the Director of the Division of Medication
Errors and Technical Support. And she will provide us an overview of the
issue and present the questions as posed in the January 28th [Federal
Register]{.underline} announcement of the meeting.

Thank you. Carol?

CDR. HOLQUIST: Good morning. It is my pleasure to present an overview of
the issues associated with the use of color on pharmaceutical labeling
and packaging.

Over the years, several different color techniques have been used on
device and pharmaceutical labels, labeling, and packaging to help
identify, classify, or differentiate drug products and their respective
strengths.

These color techniques can be briefly described as follows:

Color matching, the application of color in order to match one item with
another. This is a color differentiation technique used with medical
devices.

Color differentiation, this technique can be described as the use of
color to enhance certain features on the label, labeling, and packaging
to help distinguish or differentiate one item or product strength from
another.

Color coding, this technique is described as a systematic application of
color to aid in identifying, differentiating, or classifying a drug
product generally within the same pharmacological class.

Color branding, this technique is similar to color coding. It has been
described as a technique used to differentiate drug products within the
same pharmacological class. However, a single sponsor manages the color.

As I stated earlier, a number of drug and device manufacturers already
employ color in an effort to point out differences and to facilitate the
selection and dispensing of medication and devices. Some examples
include ophthalmologic, dental, anesthetic, and most recently, insulin
drug products.

Many individual groups endorse the use of color in this way. Color use
in such select environments as the operating room and dental suite
provide quick identification of a specific pharmacological class by the
color alone. Some state it is easier for their patients to remember the
color of their drug product rather than the name.

Many patient safety and advocate groups do not support the use of color
in this way and say the practice contributes to medication errors.
Applying color across a pharmacological class of products may contribute
to the similar appearance of drug products and lead to selection of the
wrong drug.

We will hear from a number of speakers today who should address the
following questions:

How and under what circumstances has the use of color on pharmaceutical
packaging and/or labeling proven an improvement in patient care?

Is there no discernable improvement?

What are the deficiencies in the program?

Are there specific classes of drugs where use of color has demonstrated
value?

Are there classes where use of color is a hindrance to public safety?

Are there drug products currently marketed that do not use color that
should use color to aid in identification of the drug? If so, how should
color be used?

How should the effectiveness of application of color on drug products be
scientifically validated?

We are eager to hear from each presenter today. We plan to assess the
data presented and carefully consider the next steps with regard to
appropriate applicability of color on pharmaceutical labeling and
packaging.

Thank you.

DR. SELIGMAN: Thank you, Carol.

Let me introduce then the first speaker of today. He is Mr. Charles
Myers of the American Society of Health-System Pharmacists.

Mr. Myers? Do you have any slides? No? Okay.

MR. MYERS: No, I\'m doing this without slides so no musical
accompaniment.

Good morning to all of you. I am Charles Myers. I am a staff member of
the American Society of Health-System Pharmacists. Those are pharmacists
who practice in places like hospitals, organized settings like home care
operations, HMO clinics, and other outpatient clinics, in long-term care
facilities.

These are the pharmacists that are responsible on a daily basis for not
only the logistics of drug use within those settings but also
responsible for advising the medical staff and collaborating with the
medical staff in terms of the therapeutic drug use policies that will
exist in those facilities and in safeguarding the medication use
process.

We would like to commend FDA for seeking public comments on this
important issue. This is an issue on which our members have given
considerable thought. I will tell you the punch line ahead of time and
that is that our members think that color coding is not a good idea.

Most of my comments will address color coding. Our members have
developed formal policy for ASHP about this matter and paraphrased, the
policy that our members have developed for themselves and for our
society is ASHP supports the reading of drug product labels as the most
important means of identifying drug products and opposes reliance on
color by health professionals and others to identify drug products.

You can back into the concept there that color coding then is not
something that our members support because they believe that relying on
color as a means to identify a product is not a good idea.

Let me ask you to think for a moment about a typical hospital. It could
be, however, a home care operation or a long-term care facility if you
prefer. In terms of medication use, these are incredibly complex
environments. There are so many drugs. Literally there a thousands of
drugs that will be used in a given hospital every day.

There are so many of those drugs. There are so many strengths and
concentrations, so many routes of administration, so many rates of
administration, and only a few correct rates of administration.

There are so many ways that drugs could be categorized. We know, for
example, that they could be categorized by pharmacologic class.
Antihypertensives, anti-arrhythmics, glucogenic drugs, neuromuscular
blocking agents, narcotics, pediatrics dosage forms and strengths,
emergency medications, ophthalmologics, sterile and non-sterile
products, internal and external products.

So we have great variety in the types of drugs that exist and the types
of things that colors could be assigned to mean. And therein lies a
potential problem. The matter of classification could become immensely
complicated depending on potential conflicts and drugs that have
multiple characteristics.

For example, if a green label meant a drug was an antihypertensive and a
red label meant that it was an anti-arrhythmic, how would a beta blocker
drug that can be used for both purposes be labeled? How could colors be
assigned in the case of combination products?

In hospitals and health systems, there are so many care providers to
educate about medication uses and hazards. There are prescribers of all
sorts, including specialists and nonspecialists, some employed on the
premises, and some with only occasional contact with the facility
through admission of their patients.

There are pharmacists, of course. There are nurses with varying levels
of education and training. There are respiratory therapists, dialysis
staff, emergency department staff, physician assistance, and students
and, of course, trainees of all sorts in each of those disciplines. All
these people would need to understand any color code schema developed.

There are also many potential colors and so many places and media on
which the colors would have to be consistently applied. Paper labels,
cardboard cartons, glass ampules, plastic syringes. There are so many
manufacturers of the same or similar drug products. And product packages
and appearances already change frequently, creating problems enough.

Color coding would be promptly destroyed unless colors were
standardized. And yet in the face of all this complexity, there is
little objective evidence about the safety effects of color coding in
widespread use. And there are so many patients at risk.

Pharmacists in hospitals and health systems live in that complex world.
And much of what they do is designed to ensure safety in the face of
that complexity. To them, the issues of color coding and color in drug
products are not new issues. They have thought this through.

And their short summary for you is this, color is a great
differentiator. Actions to make different drug products stand out from
one another are commendable and color can be very useful for that
purpose. However, the safety of using color to transmit information, in
other words, using color has a code, has not be sufficiently proven in
the complex world of hospitals and health systems.

Those pharmacists believe that inducing even a partial reliance on color
as a code to identify drugs or to denote specific aspects of drugs is a
seriously bad idea until there is clear evidence to support such a
practice.

Hospital and health system pharmacists are aware that in some limited
cadres of practitioners, for example in ophthalmology and
anesthesiology, there has been some experimentation with color coding.
Health system pharmacists urge us all to understand that there are some
crucial differences about those experiences compared to other more
widespread use of drugs.

In those limited cadres, the number of drug products involved is small
and the number of practitioners who have to be informed about the code
meanings of colors is also small. Therefore, the transferability of
their experiences to the larger world of the thousands of drug products
and the hundreds of thousands of caregivers who have to understand the
color meanings may not be sound.

We need evidence about the merits or dangers of color coding on a wide
scale. FDA should insist upon that in large scale real world experience
before endorsing color coding for anything other than limited cadres.

Further, we believe that objective evidence about the safety of color
coding even in limited cadres should be sought through qualified
researches in the human factors discipline.

If there are places in the world where color coding already is practiced
on a large scale for drug products, those may be useful research arenas
for assessing the safety impact of color coding.

Ultimately, we urge as well a commonsense, pragmatic distinction between
whether color coding is feasible versus whether it is wise based on the
evidence. Everything is technically feasible theoretically at a cost.

If sound research indicates that wide scale color coding enhances
safety, then as a nation, we should adopt it even if it is difficult to
achieve. However, if the evidence turns out to be equivocal, and we
believe that the evidence is equivocal at this point, then some
commonsense thought must be given to whether we should invest in color
coding.

We believe FDA has a social responsibility to consider what resources it
would require to administer a color code schema on an ongoing basis. It
seems logical to assume that legally assigned and protected colors would
also launch inevitable litigated disputes. We believe the societal
necessity and the wisdom of that expense should be considered,
especially if the evidence about safety turns out to be equivocal.

The [Federal Register]{.underline} notice of this discussion made some
useful distinctions between color coding and some other aspects of using
color. As I have said, health system pharmacists believe that color
differentiation is useful. Color branding is a new term which we
interpret as a type of color differentiation, not color coding.

Color matching is not a concept in which health system pharmacists have
developed formal policy. Importantly and commendably, however, it
appears that color matching would not require color coding so it is
likely that health system pharmacists would find color matching useful.

Again, we commend the Agency for seeking comments on this important
matter. Thank you.

DR. SELIGMAN: Do you have any questions from members of the panel for
Mr. Myers? Wiley, do you want to come up to the microphone?

DR. CHAMBERS: Wiley Chambers. You mentioned that you would like to see
proof before a color coding system was put into place. Have you given
thought to what you would view as success in such a system before you
would recommend its use?

MR. MYERS: It\'s a reasonable question, obviously. And human factors
researchers would be careful to define success we are certain. We
believe that ultimately the rate of errors would be the defining
determinant for success or not success.

DR. CHAMBERS: Thank you.

DR. SELIGMAN: Any other questions from the members of the panel? Carol?

CDR. HOLQUIST: You said your position overall is that color coding is
not a good idea. Can you describe how you guys came to that conclusion?
Is it because of the errors that were reported amongst these agencies?
Or, I mean within the hospital and retail as well? Or just hospitals?

MR. MYERS: Given the world of complexity in which our members practice
and seeing the many close calls with medications that have been confused
for whatever reasons and seeing occasional attempts, even at a local
basis, for someone to decide that certain colors should mean certain
things and then seeing errors happen, and we can find the errors
documented within the USP\'s MEDMARX system and other places, given
those realities, our members are skittish.

And they are simply saying let\'s be careful about this. We ought to be
able to find out the truth. When we know the truth, we ought to be able
to do the right thing. Until we know for sure, let\'s do the safe thing.
And let\'s ask people to read labels and not ask them to rely on
something other than reading.

DR. CHAMBERS: Wiley Chambers again. Do you think there are any
differences between within the hospital as opposed to as a general
retail that would effect your opinion on this issue?

MR. MYERS: There probably are some differences. Certainly within
hospital environments, there are many, many practitioners who will
handle a drug product. In the case of a retail practice, you may be
dealing with number one, the prescriber, and number two, the
pharmacists, and number three, the patient. That\'s a fairly limited
subset of people.

Hospitals are a very much more complex environment. So yes, there might
be some differences.

DR. SELIGMAN: Mr. Myers, thank you very much.

MR. MYERS: Thank you.

DR. SELIGMAN: Carol? Carol? Carol?

Our next speakers, I guess, are Dr. Mary Baker and Dr. Thomas Willer
from Hospira, Inc. Please.

DR. WILLER: First, I\'m delighted to be here this morning. On behalf of
Dr. Mary Baker and myself, Tom Willer, we\'d like to present Hospira\'s
position on the use of color in labeling. By the way, those who don\'t
know us, Hospira was previously part of Abbott Laboratories and became
an independent company in 2004.

In essence, we oppose the use of color coding for points listed on this
slide. We note the limited number of colors. Lighting and proximity
really have an effect on readability of labeling. We also believe, as
the previous speaker, that color coding potentially or color use
potentially discourages the reading of labels. And, again, that\'s a
major issue.

The choice of the drug based on cap or label color, again, is an issue
in color coding that presents some issues. Also, we believe that looking
at color sort of makes you mentally a little lazy and you don\'t read it
as you should.

The slide presents sort of the normal limits of color, at least for us,
on a flip-top vial for injectable products. Please note the shades of
color \-- perhaps it does show up okay. Please note the shades of color
and try to identify the number of distinct colors that could be assigned
to drug products.

If you look at this cornucopia of colors, if you will, maybe you could
get by with blue, green, yellow, red, possibly white. I counted 34
individual cap colors on this. But how many could we really use to color
code drug products?

Again, the Pantone guide that we use for labeling or label and colors is
sort of the full range of colors that are open to us for printed
labeling. And, again, it seems a limitless number of colors for the
labels and, again, the question is how many usable different colors are
available? And I think you come up with a small number that you\'d like.

While Hospira opposes color coding, we strongly support the use of color
on labeling. The use of color on labels should be used to highlight and
enhance label information, as noted here, product name, drug
concentration, and key warnings.

As noted here, Hospira is constantly updating our labeling per year to
the tune of about in excess of 3,000 labels. They are changes to our
carton, our container, our package insert, trays, and corrugate
labeling. So it\'s a very complex operation that we run.

As noted here, there are many stimuli for us to change our labeling.
Some we\'re acting in response to letters from the Agency. Others
changes in the reference list of drugs since many of our products are
generic products. Next, new product labeling through ANDA submissions
that we make.

We also do a periodic review of labeling systems or classes of drugs
such as controlled drugs or the Carpuject, which is a syringe system.

Abbott, and now Hospira, has been active in acquisition of products from
other companies or buying other companies. And that results in some
labeling standardization from the old company to ours. And lastly, we
react to complaints in the complaint system.

We\'ve dealt with the need to consider all of these label improvements,
especially through a group that we call Label Enhancement Committee.
I\'d like to let Dr. Mary Baker continue at this point. Mary?

DR. BAKER: Thank you, Tom.

I\'m Mary Baker. I\'m with Global Medical Affairs. And I\'d like to
describe to you Hospira\'s efforts with label enhancement.

Hospira has about 130 drug products. Now we\'re talking all injectable
drugs which constitutes over 600 list numbers, a list number being a
different size, a different format, a Carpuject versus a flip-top vial,
a tear-top vial, that sort of thing.

In 1992, our quality assurance group established a Label Enhancement
Committee and we have met monthly ever since. The standing committee
composition includes, medical, regulatory, label control, and product
complaint, those two groups being part of our quality organization, and
a very valuable part of our organization, the graphics group.

As Tom mentioned previously, we review complaints based on clinician
complaint. Every single complaint that gets called into our product
complaint group gets reviewed at the Label Enhancement meeting.

At the Label Enhancement meeting, our label editors provide color
labeling to the Committee. If we can obtain competitor\'s labeling
because sometimes let\'s say that the Hospira product looks like a
product from another manufacturer, we attempt to obtain that. The
Internet has made it quite nice to take a look at what the competition
does because some will put their catalog on the Internet.

We also consider the storage area. Some hospitals store by brand. Some
store by generic. Some store by both. It could be alphabetical in
general distribution. We take into account whether this will be in a
locked area such as in a controlled substances location or drug class
because frequently in hospitals, you will have oncology products stored
together or critical care products stored together as in a crash cart or
PIXIS.

Taking a look at our labeling similarity complaints from 2000 to 2004,
you will see a spike in the year 2001. That was based primarily on two
products. Number one was the heparin Carpuject system. And the flip-top
vial, which is FTV. That was based on a product called Nimbex which is
now with Abbott Laboratories.

Nimbex had two issues. Number one, it went from a hexagonal-shaped vial
to a round vial because of a change in the manufacturing location. And
there also were a number of complaints regarding the labeling.

What we did regarding the Nimbex is we did do a label enhancement on the
actual label and what we also did insofar as the shape of the vial is
that a stop sign was put on the product for, I believe, about a
six-month period to alert the clinician that the shape of the vial had
changed because what anesthesiologists were doing is that they were
reaching in back and grabbing the vial based on the shape of the vial.
And they were grabbing by touch, not by reading the label.

And as you can see in the following year, the complaints have gone down.
I also might want to add that the number of actual complaints is
probably close to half this number because if somebody indicates that
two of our products look alike, that generates two complaints, not one.

In the review process, if we feel that modification is required after
the Committee reviews it, our graphics studio will put together a number
of options for us to review, sometimes at the next meeting but usually
they can get it done beforehand and we will decide which graphic to use.

Sometimes the clinician will complain about a product but the change has
not made it into the general distribution. That is a common occurrence
with products that are only made once or twice a year. That we will make
the change but the product was not scheduled to be made for another six
months.

If there is no modification required, the clinician is notified. And we
will continue to monitor for other complaints.

We use a very low tech system in some cases to see where a product is
going to be stored. We use what\'s called a story board. And we\'ll take
a large piece of cardboard, we\'ll put our label, the other company\'s
label, if it\'s available.

And we will take a look and say okay, if you were looking at this, would
you see that there is a similarity? That\'s been very helpful in helping
us to choose colors to enhance the label.

Here is an example. Here this product is being transitioned to Hospira.
It shows three products, Ketorolac in 15-, 30-, and 60-milligram
concentrations, using a different color background, the reverse out
labeling, and we tested these among pharmacists and nurses that were in
the groups, the medical groups, and it was decided that this would
provide sufficient differentiation.

To the Agency\'s questions regarding the use of color, as the previous
speaker indicated color is a useful attribute but it is not a substitute
for reading the label. Color can enhance but will not replace the
primary identifier, which is the label.

And for an example, I\'m going to show you our Carpuject syringe system
cap color. This is how our current Carpuject product is being sold. It
has a green cap color signifying a luer tip.

Previously, we marketed the product having different color caps on the
end, which indicated the type of needle, or blunt cannula, or luer tip.
What we found out when we went to the all luer tip, which is the green
cap color, was that clinicians were purchasing the drugs based on the
tip color.

So they would buy one particular product that had a blunt cannula. And
they had another product that they would buy with the needle, which had
a different color cap, and the philosophy was if I grab the one with the
blue cap color, I know exactly what drug I have and I don\'t have to
read the label.

Specific classes where color has effected public safety, we are not
aware of major data that describes this. Drugs that do not use color
that should use color, again, color is one attribute of the labeling.
And the presentation of information is critical to accurately assess the
identification of the product.

Scientifically validating the effectiveness of color on labeling, again
rigorous market testing with different populations: color-blind, those
of us over 40, and other populations as well. We realized that some of
these products are used in the home care setting with patients and
caregivers who are not medically trained.

There would have to be a transition plan from the current to the revised
labeling. And there would have to be substantial education going across
multiple disciplinary groups, nursing, pharmacy, and physicians.

And the other thing that has to be assessed is what would be the
potential for risk of increased medication errors if somebody is used
for a product being red and now it is green, when do you get the product
that is actually turning green. Again, the distribution system does not
allow for a product to instantaneously hit the market. So it may be six
months after the ruling goes into effect that a clinician will see a
change in the label.

Thank you.

DR. SELIGMAN: Thank you.

Dr. Baker either within your suite of products or when comparing your
products to other products, you presented some data showing that there
were, you know, I think some frequency data showing the number of
similarities or reports of similarities. Do you know how often color may
have contributed to some of those confusions?

You noted, you know, the hexagonal shape of a \--

DR. BAKER: Right.

DR. SELIGMAN: \-- particular bottle. I\'m just curious as to knowing how
often color may have been mentioned as a possible source of some of the
problems.

DR. BAKER: Color is mentioned as a frequent look-alike. We get
complaints over a wide variety of topics. As, for example, they will say
that our product will look like a competitive product.

A lot of this has to do with the cap color. Tom showed the different cap
colors and that say for example, we might use the same cap color for one
of our electrolytes that some other company uses for one of theirs.
That\'s happened some \-- fairly regularly.

DR. SELIGMAN: What\'s the decision making or the thought process that
goes on in your organization when it comes to the selection of colors
either for caps or for luer tips or other kinds of products that you
produce?

DR. BAKER: There are multiple considerations. As mentioned previously,
we do look at where the product is being stored. If we are aware that a
product that has a very similar name or it is close in the alphabet to
the product either by brand name or generic name, we will avoid that
particular color family. And go to something that is totally opposite.

DR. SELIGMAN: Yes.

DR. WILLER: If I could add on one point on to that, one of the things we
do since most of our products are generic drugs, we try to adopt the
same color scheme as the innovator. So if the innovator labeling is
green, we\'ll generally follow with a green color for our labeling.

However, we\'ll also try to use the same \-- a green cap color if we
can. Because of limitations on inventory and as I showed you, I think it
was 47 or whatever number of caps, we\'re not going to keep five
different shades of green. So we may just have green, however that\'s
termed. And the innovator may be slightly darker or lighter than us. So
we do try to have a similarity.

So to some extent for the generic products that we have, they will be
color similar to the innovator.

DR. CHAMBERS: How many different colors do you use?

DR. BAKER: Quite a few. We do use the Pantone. I can\'t \-- we don\'t
\-- we do not limit ourselves to any number of colors, no.

DR. WILLER: In terms of the Pantone list which Mary brought \-- I\'m not
sure if anybody has seen this, but there\'s just literally thousands of
shades. And what we\'ll try to do is \-- this is limitless to us. But
we\'ve got to make sure that it is a distinctive enough shade to use it.

In terms of the cap color, I think we\'re far more limited \-- we\'re in
the range of 10 to 20 different cap colors.

DR. CHAMBERS: I guess more of what I was asking was if you had taken the
time to go through and figure out just how many distinguishable colors
you had options to use?

DR. WILLER: We\'ve not done that.

CDR. HOLQUIST: Wiley just asked my question. But I have another
question. Have you guys experimented not using color at all? And how
would that effect the similarity in labeling? If you can\'t \-- if, you
know, if the color wheel is so small?

DR. BAKER: When we acquired products from Sanofi and the Carpuject line,
they had all their products for the Carpujects had a green and blue
stripe on the carton and they were black on white labeling.

So where we have not experimented with it, it was an expression from
clinicians that they did not like all the products having black on white
labeling. And a green and blue stripe on the front of the carton.

DR. WILLER: We do use black and white on many of our trays for a
product. If we have 25 vials or ampules that we put into a tray, we
print a black and white tray online during the production process. So
that\'s the only time we would have black on white. But the actual color
labels would still be on the individual products. So it\'s kind of a
hybrid.

DR. MEYER: I\'m Dr. Meyer from the FDA. Both you and the previous
speaker I think made some very valid points about the downside of color
coding. But in terms of color differentiation where there is no coding,
then the choice becomes somewhat extemporaneous, if you will. I mean it
becomes the choice of the particular manufacturer.

I was curious when you\'re receiving complaints about your product
looking alike another manufacturer\'s \--

DR. BAKER: Yes?

DR. MEYER: \-- product rather than your own, is there any attempt to
coordinate your response to what the other manufacturer is doing? I
guess it appears me that they might be out doing the same thing.

And, you know, with various colors you might both be changing in ways
that continue to promulgate the problem or the other thing is whether
your changes, in fact, make you look less like Drug A but more like Drug
C. So I\'m wondering how you grapple with those kinds of issues.

DR. BAKER: We have spoken with other manufacturers with certain
products. Sometimes we\'ve changed. Sometimes they\'ve changed.
Sometimes neither one of us has changed. But when feasible, we have
talked to other manufacturers.

DR. WILLER: Mary is sort of our resident wizard on the Label Review
Committee, our Label Enhancement Committee. We are cognizant of where
products we\'re guessing would be stored in a pharmacy, whether it\'s
alphabetical or by company or by product grouping. So we try to think of
those limitations when we pick a new color or we make a change in color.

DR. CHAMBERS: Wiley Chambers. You mentioned that at one point a vial was
a hexagonal \--

DR. BAKER: Correct.

DR. CHAMBERS: \-- shape. Have you seen other configurations that \--
well, let me back up. My assumption was that clinicians found that
useful to have the differentiation. Was that what they were reporting to
you?

DR. BAKER: This was a product we had purchased from another
manufacturer. And the previous manufacturer had it in a particular
location where they were able to manufacture a hexagonal vial. And we
moved to our facility, which did not have that particular capability.

But the clinician indicated that they selected the product based on
touch because they could reach in back, feel the hexagonal shape, and
then choose the product based on the shape of the vial.

DR. CHAMBERS: I guess part of what I\'m asking is if you had the option
to remain with the hexagonal shape, would you have done so? Did you find
that a good feature? It\'s one thing to say clinicians are using it as a
feature. But it may not be the only feature. It may be in addition to
reading the label, it may be a secondary safety factor. Or it may not.

DR. BAKER: Well, again, they\'re selecting a product based on touch and
not by reading the label. So we, at that time and still don\'t have the
option to manufacture those particular types of vials.

Now what we did do is alert the clinician via use of the stop sign so
they would be alerted to that particular fact that the vial shape had
changed.

DR. WILLER: Just another example of that. I submitted the fentanyl
citrate product as an ANDA in the mid-90s and that was also originally
in a hexagonal container. And the innovator selected that, I\'m sure,
because it\'s a unique presentation. Also, it\'s a special order glass.
And normally you can\'t get it unless you buy a special mold, et cetera.

So we and the other generic manufacturers subsequently just switched to
a more normal, standard, round or circular vial or ampule. So we made no
effort to imitate the innovator in that instance.

DR. CHAMBERS: I guess I\'d still like to know if you had the option to
go to the hexagonal, would you? I understand you don\'t. But if you
didn\'t have that manufacturing limitation, do you think it was a good
idea?

DR. WILLER: I can\'t respond.

DR. SELIGMAN: In terms of color differentiation, to what degree when
you\'re producing a label and looking at issues relating to readability
and legibility, do you test, you know, different either colors or fonts
or layout schemes?

And I guess my question really goes towards the color, to the degree to
which you look at different colors in order to determine which ones
might, indeed, provide better differentiation in terms of legibility and
readability?

DR. BAKER: We actually have several methods for testing. The color we
have quite a number of pharmacists and nurses within Hospira which we
will take it to them.

We will also take it to our customers and say in your institution, which
one would be most suitable with the blue? With the green? Where do you
store it? Is this a product that is only stored in a PIXIS machine? Is
this a product that\'s only in the central pharmacy? So we will take it
out to practitioners.

CDR. HOLQUIST: You mentioned that some of your products were used in
home health care.

DR. BAKER: Yes.

CDR. HOLQUIST: Do you ever go to the patient level with those questions?

DR. BAKER: We have not at this time.

CDR. HOLQUIST: Do you think it would be useful?

DR. BAKER: It may be. There\'s a fairly limited number of products that
go directly to the patient.

DR. MEYER: If I heard you right, I understand that at time you try to at
least match the general shade of the innovator product in terms of
choosing the color for your product. And I was curious as to whether
there are any instances you know of where the innovator\'s color scheme
has been protected? Where it has prevented you from doing that?

DR. BAKER: Not that I\'m aware of.

DR. SELIGMAN: Any other questions from the panel?

(No response.)

DR. SELIGMAN: If not, thank you both for your presentation.

Our next presenter is Dr. Eric Sheinin from the United States
Pharmacopeia, USP. Dr. Sheinin?

DR. SHEININ: Thank you very much. Dr. Seligman and ladies and gentlemen,
it\'s a pleasure to be here today to be able to talk about this very
critical topic in terms of patient safety.

As USP has indicated in the past, we do not have a specific policy
regarding the use of color coding on labeling and packaging of
pharmaceutical products. However, the issue has been discussed and
debated at various times by expert committees of our Council of Experts
and by advisory panels to those committees.

The results have been consistent in that these experts acknowledge that
there may be limited instances in which color coding may be helpful.
Drug-specific color coding that spans the continuum of all drugs and
dosage forms could be challenging and possibly increase medication
errors rather than reduce them.

United States Pharmacopeia is a non-governmental organization that
promotes the public health by establishing state-of-the-art standards to
ensure the quality of medicines and other healthcare technologies. These
legally enforceable standards of quality, strength, purity, packaging,
labeling, storage, and nomenclature are developed by a unique process of
public involvement and are accepted worldwide.

Established in 1820, USP is a not-for-profit organization that achieves
its goals through the contribution of volunteers representing pharmacy,
medicine, nursing, and other healthcare professions as well as academia,
U.S. and other governments, the pharmaceutical industry, and consumers
organizations.

In addition to standards development, USP\'s other public health
programs focus on promoting optimal healthcare delivery. USP\'s mission
is to promote the public health through the safe use of medicines.

USP\'s Council of Experts generally has not supported color coding of
pharmaceuticals for the following reasons.

Color coding can encourage healthcare professionals to rely solely on
the color in selecting a product rather than actually reading the label
to identify the product being administered.

There are only a limited number of colors in the spectrum. The shades of
color would likely begin to look similar to many healthcare
professionals, especially those who are color-blind to one degree or
another.

Certain colors in poor lighting could begin to look like others, causing
products to be confused.

As evidence of the potential for confusion, USP Medication Error
Reporting Programs, MER and MEDMARX have received reports where color
similarities in labeling and packaging have caused or contributed to
medication errors.

For more than 35 years, USP has promoted the importance of collecting
and sharing experiential data from healthcare professionals. USP
currently operates two national reporting programs for medication
errors, MER and MEDMARX.

USP Institute for Safe Medication Practice Medication Errors Reporting
Program, or MER, is a voluntary, spontaneous reporting program for all
healthcare professionals to report potential and actual medication
errors.

As seen on this slide, some 9,000 reports have been received since 1991.
There\'s an opportunity for interaction with the individual reporting
the error. The information collected is shared with ISMP, FDA, and the
pharmaceutical industry.

MEDMARX, an anonymous, Internet-based reporting system that has
collected more than 840,000 medication error records is used to
disseminate patient safety information, including recommendations and
practice standards, tips for consumers, annual reports, and articles
published in peer-review journals.

Participating hospitals are able to review the data and determine how
they measure against other hospitals in the program. Further, they also
are able to track how widespread certain types of errors are throughout
the nation.

The data presented today are from the MER Program, which has specific
codes for errors related to color. Because there is no such code in
MEDMARX, reports would require direct review and could be provided to
the Agency at a later time if needed.

The USP Center for the Advancement of Patient Safety searched the MER
database to measure the number of color coding errors over the time
period of November 15th, 1994 through December 15th, 2004.

Three hundred and sixty medication errors related to color coding issues
were reported during this ten year plus time frame. The reports were
sorted according to the category index adopted by the National
Coordinating Council for Medication Error Reporting and Prevention,
which classifies an error according to the severity of the outcome.

Factors such as whether the error reached the patient and if the patient
was harmed, and if so to what degree, were taken into consideration when
the index was developed. As seen on this slide, the categories can be
grouped according to potential versus actual error and whether or not
the patient was harmed.

Slightly over 50 percent of the reports were potential errors while the
majority of actual errors caused no harm to the patient. However, 4.7
percent did cause harm, with four fatalities being reported.

Out of the 360 records, 50 indicated a mode or the phase of the
medication use process where the error was initiated. The highest
percentage of medication errors occurred in the dispensing mode. This is
the phase in the medication use process where the medication is
dispensed, normally by the pharmacist, to the patient or to a unit
within the hospital.

Products involved in these harmful errors include the high alert drugs
heparin, magnesium sulphate, and potassium chloride concentrate for
injection.

This slide shows an example where there\'s two different strengths of
Dopamine injection where the color and labeling on the two packages are
identical. This is one type of packaging where color coding would not
add to the differentiation of the two strengths and thus would not, on
its own, prevent an error from occurring.

On this slide, two examples that led to fatalities are listed as well as
a third example of a serious error. In the first example, the patient
died when nitrous oxide gas was administered instead of oxygen partly
due to the inability of a technician to distinguish between the adaptor
colors.

The oxygen flow meter\'s index safety system, designed to assure
connection only to oxygen wall outlets, had been broken when inserted.
Additionally, the technician had difficulty distinguishing between the
blue nitrous oxide and green oxygen adapter because the radiology suite
where the medical gas was administered was dimly lit in preparation for
a CT scan.

The patient died as the result of nitrous oxide poisoning.

A second patient died of heart failure as the result of a nurse flushing
his IV line with potassium chloride instead of heparin. Both drugs were
in the patient\'s medication drawer. The drugs were in similar-sized
vials with similarly colored labels.

In the third case, a patient was administered anesthesia for a surgical
procedure. The anesthesiologist administered sufentanyl 75 micrograms by
mistake instead of 75 micrograms fentanyl. The patient experienced a
temporary respiratory arrest and his oxygen saturation decreased to 80
percent.

Narcan 0.2 milligrams was administered and respiration was supported.
Surgery was cancelled and the patient returned to the nursing unit. The
patient was eventually discharged with no problems and the surgery was
rescheduled.

The anesthesia section had this concern regarding the possibility of
being unable to distinguish the red labeling of fentanyl from the green
labeling of sufentanyl secondary to the high prevalence of red-green
color blindness in the male population.

While the idea that standardizing the appearance of labeling and
packaging would reduce errors has merit, in reality it is untested.
However, there may be some value to such an approach if it is applied
across the market rather than across drug classes.

The concept of black and white labels for all prescription drugs also is
worthy of discussion. At a 2003 USP-sponsored patient safety stakeholder
forum, there was considerable discussion on the use of color coding. Ms.
Diane Cousins, Vice President of the USP Center for the Advancement of
Patient Safety, suggested the concept of black and white labels for all
prescription drugs.

Black and white labels would include standard formats and placement of
information similar to the format found on over-the-counter products.

Food products also have a standard format and placement. Black and white
labels would create similarity among products that would force a patient
or healthcare professional to read the label. Further, the information
sought would be easier to locate in the standardized format as seen on
the OTC and food products.

Anesthesiologists have used color coding by drug class for years in
their practice. But this practice deals only with a limited number of
products.

Considering the number of products in the marketplace, an array of
distinctive colors would be next to impossible to achieve. Certain drugs
within a class often have different characteristics, pharmacologic and
pharmaceutic, that could be harmful based on the clinical condition of
the patient.

For example, substituting or selecting one statin for another could
result in the administration of a higher dosing profile and lead to
liver toxicity.

In closing, USP supports the suggestion that caution is needed regarding
the use of color coding for pharmaceutical products to prevent
medication errors. And if used, it should be on a case-by-case basis.

USP is very interested in working with stakeholders to examine how
changes in product labeling, packaging, including colors, and/or
nomenclature could have a positive impact on medication error
prevention.

The 2005 UPS Convention will be held later this week. Among other
responsibilities, the convention members will consider a number of
resolutions that will direct much of USP\'s activities from 2005 to
2010. One of the resolutions that will be considered relates to this
issue.

If adopted by the convention, two of USP\'s expert committees, which
consist of scientific experts in drug packaging and medication error
reduction, along with our staff, would address this issue.

I think you for the opportunity to participate in this hearing and for
your attention. Thank you.

DR. SELIGMAN: Thank you, Dr. Sheinin.

Any questions from members of the panel?

Carol?

CDR. HOLQUIST: You stated that in your USP forum, that you proposed that
black and white labels be used with a standard format. What data was
used to support that recommendation?

DR. SHEININ: I\'m not aware if there were any data. No, there were none.
It was just an idea, a thought that as I indicated, would force people
to look at the labels. I mean personally, from what I have seen through
my career at FDA and now at USP, many of the errors are caused because
the dispenser or the administrator of the medication is too rushed and
just doesn\'t look at the label. They rely on other things.

To me the solution is to train them you have to look at the label and
check it. I\'m just speaking for myself now. This is not USP. But
doesn\'t a nurse, when they come in, check the patient\'s band to make
sure they have the right patient? Well, I think it is equally important
to check that they\'re administering the right drug.

DR. CHAMBERS: Of the medication errors that you mentioned that caused
death, one of them was a difference between oxygen and nitrous oxide.
And that was a plug in. I\'m not sure \-- unless you can help me \--
where would you put a label in such a case?

DR. SHEININ: I guess there could be a label on the adapter. That
situation obviously was complicated by the fact that the connector was
broken. As you know, the medication gases, medical gases, when
delivered, the connectors are designed so that only certain male fits a
certain female. But it doesn\'t always work that way.

And I know you\'ve heard and I\'ve heard over the years of situations
where something is broken or a technician actually forces something in
because they think it\'s the right connector. But the connectors
certainly could have a label on them as well as the container has a
label.

DR. CHAMBERS: I\'m just thinking since most of the errors tend to occur
because multiple safety factors break down and that sounds like what was
going on. I mean not only did it not fit in the right size, there was a
color coding to try and help it. My guess is there\'s also a marking of
what each of the two things were on the containers.

But in spite of that \--

DR. SHEININ: Right.

DR. CHAMBERS: \-- it still wasn\'t.

DR. SHEININ: Exactly.

DR. CHAMBERS: But to take away some of those, I\'m not sure would be \--
if you were to go to say all black and white, then we\'ve only got two
safety features as opposed to three. And yet we saw an error occur even
with three.

DR. SHEININ: Right. And as I indicated, there could be color coding on a
case-by-case basis. One of the things that I mentioned was
anesthesiologists using color coding but yet there was a mixup there
with the sufentanyl and the fentanyl.

So nothing is failsafe. I think we have to do everything we can do to
try to prevent errors. I don\'t think there is any system that will
totally prevent medication errors.

DR. CHAMBERS: But do I understand correctly it\'s USP\'s position that
some color coding in limited areas is helpful just not widespread?

DR. SHEININ: Right. Yes, we did support the color coding of the ferrule
on concentrated potassium chloride injection with a black ferrule.

DR. CHAMBERS: Was that the error that you mentioned that the cause of
death was that not the label of those were \-- let me back up. Sorry.
The potassium was not with a black cap at that point in time?

DR. SHEININ: It probably did have a black cap.

Yes, Bob?

DR. MEYER: Just following up on that last comment about the specific
sort of, I guess well demarcated areas where the color coding might be
helpful. Are there any circumstances or other means that the USP sees
that where such instances can be identified where perhaps some area of
practice or some particular kinds of drugs are sort of ripe for color
coding.

DR. SHEININ: Nothing that I can report at this time. But if that
resolution is passed, and I have every reason to believe it will be, we
have a Safe Medication Use Committee and a Packaging and Storage Expert
Committee that will take that issue up over the next five years and
hopefully make some recommendations.

And we do have the ability to sponsor open conferences where we can
solicit input from the public, from interested parties. And I would
think that would be one mechanism that we would use to go forward with
that.

DR. CHAMBERS: The proposed resolution is in favor of using color or not
in favor of using color or it looks to examine it?

DR. SHEININ: I don\'t know the exact language but I believe it goes
something along the lines of USP resolves to look into the situation.
Very few of our resolutions are so pro or con.

We did have one which you probably would be interested in \-- maybe not
you Wiley, but Bob \-- Robert, for this current cycle, there was one
suggesting that we look into the advisability and feasibility of
developing a standardized imprint code for solid oral dosage forms for
poison control centers and physicians when an elderly patient comes in
with a bottle and dumps it on their desks and says what are all these
things?

And it was very heated discussions in a group that we put together to
discuss it with industry on one side and practitioners on the other
side. And no consensus was ever reached.

So I would hope if we go forward with the color coding issue we could
come to some sort of a consensus.

DR. SELIGMAN: Of the 360 cases that you presented over ten years where
color appeared to have played a role in the medication errors, were
there particular types of drugs or classes of drugs or features related
to the use of color that accounted for those errors?

DR. SHEININ: Not that I\'m aware of. Shawn?

MS. BECKER: I think you listed the most significant drugs that we were
seeing, you know the high alert drugs seemed to be causing the most
problems but I\'m not aware of any other color issues.

DR. SELIGMAN: Other than the drugs, there was no particular types of
colors or certain features related to the use of color that may have
accounted for or contributed to the errors?

MS. BECKER: I think it\'s just the similarity of the colors when
products look the same.

DR. SELIGMAN: Okay.

DR. SHEININ: I\'d like to just add one thing in response to one of your
questions to Dr. Baker previously about matching the presentation of the
innovator. I personally think that\'s critical. If at all possible, any
generic product should have packaging and labeling that looks like the
innovator\'s to avoid medication errors or confusion among the patients.

DR. SELIGMAN: Thank you, Dr. Sheinin.

DR. SHEININ: Thank you.

DR. SELIGMAN: We are running a little bit ahead of schedule which is
just fine. We\'ll take a 30-minute break and reconvene at about 9:40.
Thank you.

(Whereupon, the foregoing matter went off the record at 9:13 a.m. and
went back on the record at 9:43 a.m.)

DR. SELIGMAN: If you all take a moment and return to your seats, I\'d
like to begin again.

Our next speaker is Dr. Michael Cohen. He\'s the President of the
Institute for Safe Medication Practices. Dr. Cohen?

DR. COHEN: Thanks very much. Good morning everyone. I thought the
speakers so far have done a great job and I appreciate their input
personally as well as for FDA.

This is something that\'s been of interest to me for quite some time.
And I thought what might be helpful is to perhaps demonstrate some of
the problems that we\'ve have with the application of color. So I\'m
going to take the opportunity this morning to not just answer the
questions that have been posed but also to show, you know, some of the
issues that have arisen over the last 30 years with the Medication
Errors Reporting Program.

We work with USP and the Medication Errors Reporting Program, as Dr.
Sheinin mentioned. We also work with the Pennsylvania Patient Safety
Reporting System in the Commonwealth of Pennsylvania, the hospitals,
surgery centers, and birthing centers.

Under Act 13 in our state, it\'s mandatory for them to report medication
errors to our organization on behalf of \-- which we collect on behalf
of the state\'s Patient Safety Authority. We also share our information
with FDA and under a Freedom of Information Act request, we are able to
obtain reports of medication errors as necessary.

I just want to define again \-- go through \-- I know it was defined a
little bit earlier by Dr. Holquist in the beginning the differences
between color differentiation, color coding, color branding, and color
matching. And I just thought it might be helpful to say a few words
about that and also give an example of each so that you truly
understood.

I have to say that to my knowledge, we really haven\'t seen much in the
way of color coding of commercial pharmaceuticals. I suppose that the
potassium chloride concentrate for injection with the black cap would be
considered color coding although I\'m not sure everyone actually knows
that when you see black, that means potassium chloride concentrate
because that\'s the only parenteral product that is allowed to have that
color or lack of color I should say.

But I\'m not familiar with too many other products. Possibly the
dopamine strengths \-- at one time one was orange, one was red, and one
was green. And I believe there was a requirement for dopamine to
identify the strength. I\'m not sure how helpful that was.

Outside of that, I\'m not real sure if we\'re really talking about color
coding today or color differentiation because there really hasn\'t been
much use of color coding.

Color differentiation, I think that can be very helpful. And I\'m going
to show you an example or two. And as we go along, you\'ll see
additional ones. This is to differentiate features, different features
with specific products. It can be used over a long range of products and
some companies have attempted to do that.

But as Dr. Meyers mentioned in his talk, it becomes very difficult
because over a period of time, additional companies will also come out
with products in similar sized containers, et cetera, which will have
similar colors. And there\'s really no controls over that at this point.

So color differentiation over a wide array of products within a
manufacturer\'s line can occasionally present problems. And I want to
show you some good examples of that.

Nevertheless, it can also be helpful in drawing attention. That is color
can draw your eyes towards important label information. And I\'ll show
you some examples of that as well as the use of color to help to
differentiate two drugs names that are similar.

This is color differentiation. All the way over on the right, the pair
of products there are both adrenalin chloride solution. I think when you
look at this carefully, you may be able to see that there is actually a
difference between these two containers. However, this was not evident
to people working within a hospital when they had to store these drugs
on a crash cart for the emergency room or for other areas of the
hospital.

One is for topical application. And the other one is for injection. And
every once in a while, we would get a report of somebody placing this in
the crash cart instead of the hypodermic. And at the time, there was
widespread use of high-dose epinephrin, which was the reason for the
presence of these 30 milliliter vials.

And so during the code, someone would open the cart and open the vial.
And unfortunately it had a screw cap and it just delayed application of
the drug.

And so many of us communicated with the manufacturer at the time,
Parke-Davis, and they agreed to help by differentiating the products \--
oh, there\'s a better one here \-- there we go \-- by using this
background color. And so immediately people were able to see the
difference.

Although I would have liked to have seen something that would have also
drawn attention to the fact that this was topical because you still
couldn\'t see the vial inside. However, this really did help. And I
don\'t recall getting repeated reports of medication errors once these
new drug vials with the color differentiation reached the user
environment.

Color matching is a little bit different. This is kind of a blue plug
goes into a blue socket. And I know of \-- this is a good example of
something that works pretty well in the area of color matching. This is
Dr. Jim Broselow who, I notice, is going to be a speakers later on
today, and he has the Broselow Tape, which is widely used in emergency
care.

You put a baby, for example, you lay them out on the tape and you
actually measure what color they are. Once you have that color, you can
have a crash cart, for example, that has drawers that takes you right to
the proper size airway, the proper size for endotracheal tube, the drugs
that would be used in that length child, et cetera, et cetera. So this
is color matching.

You could also use this type of color matching on a drug label. So you
could put the doses of different drugs for different ages on a drug
label. And you\'d be able to do that as well. And there\'s other ways
like dose packs, et cetera, that would actually match the color.

This has been very successful in many ways. And it\'s being improved as
time goes on and new applications will be developed.

As far as color coding, this is, as Dr. Holquist said in the beginning,
a very systematic application of color that really identifies specific
information about the product. The one that I do know, and I forgot to
mention this at first, that was supposed to be a color coding scheme is
the ophthalmics.

And, you know, I think what you\'ll see and what you\'ll hear is what
works well in one environment may not work well in other environments. I
know Dr. Meyers said that as well. And that\'s really true with the
ophthalmics.

As far as the ophthalmologist\'s office, great. Tan means an
anti-infective, pink anti-inflammatories, yellow means beta blockers, et
cetera, et cetera. And they\'re able to take a look at this color and
then use that medication.

Probably in the patient\'s environment, in their home, that\'s helpful
in differentiating the different types of ophthalmic products.

Take those same products, not just one or two but scores of specific
color within a range and put that in an ambulatory procedure unit, short
procedure unit, or in a pharmacy, community pharmacy, where often they
may store by drug name, either generic or brand, or even by drug
company, and you would begin to see that you have dispensing errors,
which is exactly the experience that we\'ve had with the ophthalmics.

And I was unaware that this was going to happen when these products
first reached the market. We were quite surprised, and we did, in fact,
receive a number of reports of mix-ups.

Color coding, research-based evidence regarding the use of color and
reduction of medication errors, I\'m not familiar with. I know there is,
in fact, research going on in two centers right now looking at color,
one in the U.K., one that we\'re sponsoring in Texas.

And some of the early results do show that, you know, color coding
actually does not help to prevent medication errors. We\'ll have to take
a look at that as time goes on.

Although color coding may help to differentiate drug classes, as I said
with the ophthalmics, it may increase intra-class medication errors.

And two I have here, Example 1, color code by drug class and various
drugs within a class may be confused wit one another or a color code by
drug and various strengths or concentrations for that drug may be
confused.

This is a color code scheme that is in wide use in operating rooms.
It\'s kind of faded. The neuromuscular blockers or muscle relaxants are
a much different color red. They look kind of pink here. But this is
actually used in operating rooms really around the world, not just in
the United States. U.K. has implemented a process like this as well.

And actually we support the use of these user-applied color-coded
labels. You\'re working again, as Dr. Myers said, in a small environment
within the OR with people who truly understand the meanings.

I would shudder to think what would happen if somebody applied these to
the critical care drugs that might be used in the OR environment but are
also used in the intensive care unit, the emergency room, and out on the
med-surg units at the same time without a true understanding on the part
of the health professional what the meaning of these colors actually
are.

And I think that\'s a big problem We have not been trained in our nation
to identify the ophthalmic color codes, those of us in pharmacy school,
those of us in medical school.

And I think one of the lessons that we have from that is \-- and nursing
school \-- and I think one of the lessons that we have from is if
you\'re going to do anything at all with color coding commercially, you
have an educational campaign to conduct. People have to really
understand what these colors mean.

And they have to understand some of the problems that are associated
with this. You cannot just do this wholesale without some type of
education being provided. And unfortunately, that is not a real
high-level strategy as far as preventing medication errors. Education
that is.

Too often people somehow miss that education or they don\'t understand.
Or they lose the knowledge over time.

But this is useful in the OR with a small number of individuals and a
small number of drugs in an enclosed environment. I\'d worry about it
being used outside.

One of the things that we had hoped actually to happen, similar to the
potassium chloride concentrate, which has the black cap, and which early
on I actually believed that although it certainly didn\'t prevent the
errors and people would draw it up in a syringe and not label the
syringe and then, you know, inject it directly intravenously into a
patient and cause an arrest, it did help to differentiate the potassium
product from all other products.

And I do believe that there was a decrease at least in the number of
voluntary reports that we were receiving. Certainly not scientific by
any means. I\'ll talk about that later using a voluntary program to
even, you know, indicate in any way what actually might be happening is
very misleading. And it should never be done in that way.

But we did hope that at least we would have been able to use what we
call anesthesia red. This was an ASTM standard but it would have been
used sparingly on a drug vial. The cap perhaps, a border around the drug
name, but along with other enhancements like the drug name itself, the
strength, et cetera, et cetera.

And I do think because this is a drug that if it is accidently mixed up
with any other parenteral product and accidently given to someone who
isn\'t intubated, who isn\'t receiving artificial ventilation of some
type, they\'re going to stop breathing. They\'re going to be totally
paralyzed. They\'re not even going to be able to tell you that there is
a problem. So it is a real danger.

We thought that, you know, applying this color code which would indicate
neuromuscular blockers would be very valuable. Unfortunately it did not
make it through the entire process over at USP. And at this point, I
understand that it is only going to be the warning \"paralyzing agent.\"
But that might have been a use for color coding.

We know we\'re supposed to read labels three times. All healthcare
practitioners learn this when they\'re dealing with medical products.
Certainly nurses, and pharmacists, and physicians.

But unfortunately from time to time, we have our eyes drawn away by
other material. And I use this slide to show you it ain\'t just about
the color. And, you know, you can test all you want the color. That is
only one variable. And a couple of our speakers have already mentioned
that. It is a single variable.

There are other variables that absolutely require consideration. On this
label, which I think is very poorly designed and has caused medication
errors, you will see most prominent the drug company name at the top of
the label within a blue band. I think your eye is drawn to that
immediately.

You will see possibly in some cases an eye instead of, you know, well,
not instead of anything \-- that also, I think, catches your attention.
You will see very small fonts, which are not Helvetica-type fonts or
Sans Serif-type fonts, which are a little bit more difficult to read.

You will see a lot of wording. I think you will see similar colors
within a class and you would begin to understand how easy it would be
for a nurse or a pharmacist to mix these up in their practice. And
that\'s exactly what has happened with these products.

So I think an important lesson is to never rely on a single variable
such as color. One must always take into account the amount and size of
text, the \"corporate dress\" we call it, including the fonts, the
shape, the size, the logo, the backgrounds that are used, the manner in
which corporate identity is expressed. Similar strengths is also
something that can be very misleading. And all of this is extremely
important.

And we have found in our experience anyway that the more highly stylized
these labels are with that corporate look, and some of the designs that
we have seen now are just so distracting to me, it\'s going to draw
attention away from the real purpose and that is reading the label.

And to better understand, this little experiment is useful. This shows
how just one variable can really confuse things. Nobody would
misunderstand the meaning of each of these words. And if you were
playing cards and somebody said clubs, diamonds, you\'d know exactly
what we\'re talking about.

And likewise, I don\'t think anybody would misunderstanding this. But
what happens is when you distract people and put two of these variables
together, it becomes very difficult, I think, to read the label or
understand. And it is very misleading.

It leads the practitioner in the wrong direction. It makes it very easy
for a medication error to occur.

There\'s a potential considerations with color for label, the potential
for mix-ups within the class must be considered. And just to focus a
little bit more on the ophthalmics, this is a category that has a single
antibiotic, a single sulfonamide, and antibiotic combination with
steroid added, and this is an ophthalmic ointment, this is a solution.

Here\'s the differentiator right there, the one word and the one word,
which is very difficult to see. And sometimes these are not opened in a
community pharmacy. That\'s one difference between community and a
hospital. The labeling would be applied to the outer carton so it might
not even be recognized and the patient would get the wrong dosage form.

This is a combination of just antibiotics. This is a combination of
antibiotics in an eye ointment. And this is another combination of
antibiotics along with a steroid. The combination of antibiotics and
steroid are a little bit darker in color than the other.

This is pretty close to the real world, by the way. So you can see how
easy this color code scheme would have been mixed up.

These are three different beta blockers that are color coded by the
ophthalmic color code scheme. And I think you can really see here how
each is 0.5 percent. Your eyes are immediately attracted to the 0.5.
That\'s what you see.

You see the drug company name superior to anything else on the label at
the top. You see the logos, this corporate dress that I speak of. And
it\'s very difficult immediately to tell the difference between these.

And here\'s what happens. These do get stored together by accident
sometimes. A technician, a nurse, will take the container, think she has
the right thing, and then throw it in with all the other products that,
you know, and even though they\'re not the same product.

When someone else comes by in the pharmacy and chooses one of those
items, they\'re going by the drug name but it might be on the outside of
a bin that it is stored in. So they see the name there, they put their
hand in, and it\'s assured that this is the right drug. And never
actually see the drug name because they\'re so mislead by the
similarity.

Here\'s another example of the ophthalmic confusion. Again, with very,
very highly stylized labels that probably communicate Ciba Vision better
than vasocidin. And I don\'t know if that\'s still on the market or any
of these are. But these are from my library.

So considerations with color on labels, first of all, I think you
absolutely \-- if you\'re going to do this, I don\'t care what it is,
you have to have practitioner testing with prototypes. These are the
people that use these. They know their environments. And it should be
tested within their environment using a failure mode and effects
analysis process.

And that can be done fairly easily with graphics and a questionnaire
that drives them to answer. Will it be 100 percent? Is it scientific?
No. But I don\'t know that you have to be scientific with something like
this or that you could even be scientific. There are just so many
variables as Dr. Myers talked about in his opening speech.

So you have to consider the environment of use and work processes. What
works well in an ophthalmologist\'s office may not in other areas. What
works well in the OR may not. What will it be stored next to?

It depends on how the storage is accomplished, which is a variable. What
other drugs within the color class might it be confused with? And many,
many questions would have to be asked if this was done.

Most of us are familiar with this process of failure analysis. How you
literally would set up a process flow diagram and determine what might
go wrong. Now this has been applied to testing products in the user
environment. And it should be something that\'s required by FDA.

Consider the process flow \-- well, I\'ll just bypass this because this
is \-- these are the kinds of things that you would look at. Not all of
them \-- this is not all inclusive. But how things are ordered, how they
reach the inventory, how they\'re stored, the light in that environment,
you know will it make one color look like another color, space, relation
to other items, drug delivery, who are the users going to be, where is
this going to be sent, and so on and so forth.

And when I say user environment, what just looks so perfect on a
two-fold blow up of a label on a flat, you know, table on a piece of
paper, when you put it into the user environment, it can look very, very
different.

So here we have on the product on \-- a whole sleeve of products on the
left of cefazolin 1 gram and on the right, we have cefazolin 10 gram.
And I turned the vial around so that you could see that.

But this is how it might actually be stored in the user environment. And
then name of the drug is almost cut off. And depending on the height of
the shelf, it would be cut off. And these are the kinds of
considerations that practitioners would need to make.

You have a cover here \-- I\'m not sure if this is on the market anymore
\-- but basically they\'re sealed. It says sealed for safety almost
obliterates the readability of this product label. So imagine that in
addition, we also had similar color caps and labeling, et cetera, et
cetera. It would be a disaster.

Here\'s another problem that we run into especially with parenterals.
The caps pop off. And they may not stay on. So it can make one product
look like another even if one of them does remain with a color-coded
cap. So that has to be taken into consideration as well.

The Carpuject syringes, they\'re all green. How many people would know,
taking a look at this quickly, that on the left is demerol, in the
middle is morphine, on the right is hydromorphone. And there\'s quite a
difference in the potency of these agents.

So, again, you need the practitioners to put these in the environment in
which they\'re going to be used. And think about what might be confused.
And it\'s a very, very useful experiment to see this happen.

People are pretty clever. And they will show you how you might err \--
or what misleading path you might take.

Here\'s an ophthalmic container that looks like glucose control
solution. For some time, we had problems with ophthalmic containers that
looked like the Hemoccult or Seracult that was used as a guaiac stool
test.

And this is a hydrogen peroxide solution that\'s rather potent and would
be placed in patient\'s eyes along with alcohol and it was a very, very
painful experience for the patient. So that has to be considered as
well.

You don\'t know what it\'s going to be mixed up with essentially.
Here\'s two other drug vials. They certainly look alike and one of these
gets thrown in the other bin, I really doubt that a nurse or an
anesthesiologist would pick this up. If it says that it\'s enalapril or
Vasotec injection is the brand name for Merck\'s enalapril, not this
one, that it also looks like pancuronium.

I think that would be history. Pancuronium is a paralyzing agent and
probably would cause someone\'s death if they weren\'t intubated. So,
again, you know, we have this situation where the user environment is a
little bit different.

Here\'s partially turned vials. Azatheioprine on the left inamrinone on
the right. Vecuronium, another neuromuscular blocker, acetazolamide on
the right. Quite frankly, this goes beyond color coding, color
differentiation. This should be done, in my opinion, for all products
that are going to be marketed.

I think manufacturers should conduct user testing. And be able to
present that information to FDA.

Very specific, unusual colors sometimes are misleading. We don\'t see
this color purple very much. And we got reports of some mix-ups here
because people got used to that color and thought it was unusual and
that it specified a specific drug.

A similar situation here with these products. So you can see what I\'m
talking about.

Here\'s one the Department of Defense had a problem but we had problems
all over the country with this. This is a different type of color
coding. It\'s for a syringe. And basically I can get a better picture of
this. Same problem here, different brands.

For many, many years, insulin syringes were color coded orange. And then
the International Standards Organization told all the syringe
manufacturers if they want to market their syringes worldwide, they have
to meet their color code standard. And the color code was by needle
gauge, not what type of syringe.

And the needle gauge for 25-gauge was orange. And what happened was we
had this rash of events that were getting reported to us where the
nurses were confusing tuberculin syringes with insulin syringes.

And what would happen the tuberculin syringe is a 1-mL syringe and the
scale is in tenths of a milliliter. Except there was no zero in from of
the decimal point. It just said .6. And the nurses would take a quick
look at this and if they needed to give six units or eight units of
insulin, they would draw it up to the .8 without realizing there was a
decimal point there or a period there.

And instead of the patient getting six units, they would get 60 or eight
units, they would get 80. So this is color coding and the way that it
was applied was just a total shock to the practitioners. They were never
taught about this. And we had this rash of very, very serious errors.

So this is not the way that products should be introduced if color
coding is going to be used. Please.

Now since then, one of the companies at least has changed the color
scheme and it does seem to \-- they have about 80 percent of the market.
And it does seem to have been \-- the problem does seem to have
subsided.

Consideration with color on labels again, haphazard application of
multiple colors to differentiate products must be avoided. Again, take
into account the amount and size of text, the corporate dress, the
fonts, the logos, and so on and so forth.

This has been a real disaster, this particular problem here because it
has effected hundreds of patients. And I\'m not sure but I believe it\'s
still on the market and additionally causing problems. CDC wrote about
this in [Morbidity and Mortality Weekly Report]{.underline}. Several of
the state health departments wrote about this as well.

And the problem very simply is nobody knows what these colors mean. They
have no meaning. And they\'re very, very difficult to follow or even
differentiate because they\'re very unusual colors and not just one but
two and three different colors on the same label in some cases.

And also, within the circle, total inconsistency. Here the five means
tuberculin units. Here it means milliliters. Here the number is the
number of doses. I think you can see the problem.

We had over a 100 patients in California alone that received instead of
PPD injected intradermally, received TD, tetanus and diphtheria toxoid
vaccine because of the mix-up. So when you\'re talking 100 patients,
that\'s a lot of different healthcare practitioners that have made this
mix-up.

Then we had flu vaccine given instead of PPD.

We\'ve had these others mixed up. The DoD actually did send out a
warning to their entire \-- all the military hospitals to warn them
about this.

Polio virus vaccine confused. Tetanus toxoid vaccine confused, et
cetera. This is bad use of color coding. And it\'s exactly what you want
to prevent.

Rocket stripes on \-- one manufacturer\'s products were very misleading.
They all had these green and blue rocket stripes. And people\'s eyes
were attracted to that. And if you go back into the data, you\'ll see
mix-ups between different critical care drugs.

So this is \-- it\'s very important how this color is applied. But
again, it is not just the color. There is a lot more that it involves.
And as I said, the fonts, and the position of the color, and what it
draws attention to, and so on and so forth.

It should primarily draw attention, in my opinion, to the drug name and
it shouldn\'t say dose. It should say strength. But also the amount in
the container, the total amount in the container. And I think that has
occasionally misled people and caused medication errors.

So I think \-- this is an example of what I\'m talking about. Here at
one point Merck had unit dose packaging that was black and white. And,
you know, people would read the label and hopefully differentiate. But a
lot of people didn\'t read the label. And I think they were fooled by
the bar code and the similarity on the two unit dose packages, et
cetera.

One fix was to place a yellow \-- color bands for the different types of
drugs. But unfortunately what they decided to do was color code it by
strength. So your eyes were drawn to the strength. And it didn\'t take
long for the two 20-milligram products to be confused.

One of the other manufacturers used the color band to draw attention to
whether it was, I think, sustained-release product or a delayed-release
product in this case. That was Astra Merck.

More recently this product was changed to this product which is now this
designation. Not the same product. This is Singulair.

And now we have a problem because the attention is drawn to the drug
name but they don\'t do a good job drawing attention to the strength.
This is a four milligram and this is a five milligram. Again, I think
practitioner testing absolutely would have picked this up before it
became a widespread problem. And I know the company is concerned enough
to be working on a third revision now for the unit dose package.

Here\'s others. Hydroxyzine gentamicin, thorazine suppositories,
compazine suppositories, compazine pediatric, compazine adult.

Here\'s one of the companies, they actually used these color code bands
internally to identify products in production before they had the label
on it. And, unfortunately, when these get out on the nursing units, they
make things look exactly alike. And it\'s self-serving. It doesn\'t help
the practitioners avoid errors.

Here\'s the use of color to draw attention to only a portion of the
important information. That is the strength per milliliter. What they
overlook is that it is a five-milliliter product or actually 500
milligrams.

They did this with other strengths as well. And I have to say we
published an article in [Annals of Emergency Medicine]{.underline} about
some deaths with Ketalar as the result of drawing attention to the wrong
portion of the label. And people thinking the entire container had 100
milligrams when it didn\'t. The entire container had fivefold more than
that.

This is one that we\'ve had a lot of problems with. Fortunately one of
the manufacturers decided to eliminate this presentation and has gone to
a drug vial instead. On the left, Methergine, which is an ergot
derivative. On the right \-- I\'m sorry, on the top, Brethine
(terbutaline), used for totally opposite purposes in obstetrics.

You would find these products in the delivery room. And if you had
somebody that was having uterine contractions prematurely, they would
probably get Brethine or terbutaline as a tocolytic. It\'s an off-label
use, I understand, for that.

Unfortunately, people were getting injected with Methergine, which
causes uterine contractions. And this has gone on for quite some time.
And fortunately one of the manufacturers, as I said, has eliminated.

This is color in the packaging, though. And those little color bands
that I talked to you about that mislead people.

Here\'s color on an OTC product. You totally overlook the fact that this
is benzocaine, which some patients might be allergic to because you can
certainly see everything else is very, very similar. So here\'s they\'re
not drawing attention to important information.

It can be used successfully to differentiate products, to draw attention
to important information, to enhance recognition of unique letter
characters. So let me show you that.

I already did show you this. That certainly helped to eliminate this
problem.

We had a problem. This actually was attacked in a couple of ways. This
is a long-standing problem in medicine where people would order or
dispense the wrong drug. Hydralazine instead of hydroxyzine. Both are
50-milligram strength.

And you can see when a company puts everything together in the same
color patterns exactly, including the strengths, how easy it would be to
mix these products up especially when other products within their line
are different colors. So you would certainly think these two blue and
orange ones must be the same thing. This is old though.

And this was addressed with \"tall man\" letters to differentiate the
characters in the drug name that are unique. We actually have some
studies completed now that show the value of \"tall man\" letters in
preventing mix-ups between two look-alike drug names.

And the other thing that was done is reverse print and the use of color
to help differentiate these products. And frankly, I think this is
working pretty well. So that\'s a good use of color.

Here is another good use of color. On the left, Doxil. This is a
liposomal form of doxorubicin. And the does of this product can be much
lower than the typical doxorubicin product. It should be much lower.
Unfortunately, people didn\'t know that.

And if they would get an order for doxorubicin and not recognize that
this is quite different as a liposomal injection, and requires a lower
dose, unfortunately they would give this drug but use the higher dose of
the conventional product.

And I think one of the things that helped prevent this was to have a red
color band to draw attention that it must not be substituted and that it
is a lipid-based formulation or a liposomal formulation.

I think they could have done even more than that but I think that this,
along with a lot of feedback to the field on medication errors that have
happened, has, in fact \-- it\'s been a while since we actually had an
error reported.

Here\'s another great redesign of a product. They had mix-ups between
cisplatin and carboplatin. And here is the use of color and a stop sign.
It says, stop, verify the dose, drug name and dose. And this is
cisplatin, using color and elevated font to differentiate this from
carboplatin, which the dose is very, very different. Carboplatin is a
much higher dose than cisplatin.

And here as well. And there were other features for this product as
well. And this has really helped to eliminate this confusion between the
two drugs. So this is another good use of color.

Here\'s the use of color to draw out the letter characters that are
unique. There is acetazolamide and acetohexamide, an anti-diabetic drug
not used very much any more but still around to my understanding. And a
mix-up there could be fatal, has been fatal. We know that we had a case
in New Jersey several years ago.

And so more recently \"tall man\" letters have been applied by FDA but
this is an example of how one of the companies took color to help
differentiate the letter characters. I think that was helpful and could
be used in combination.

And has been used in combination for other trademark issues where we
have lookalikes like Zyprexa, Zyrtec. If you take a look, they use a
color background. They use italics. They use a different font than the
rest of the word.

The same thing with Lamictal to reduce confusion with Lamizol. And I
think this can be very helpful.

So final recommendations, practitioner input, expert analysis also.
It\'s not just practitioner input. It\'s gathering the data from the
practitioners and then having an expert panel take a look at that and
perform their own failure analysis using failure mode and effects
analysis methods.

I don\'t believe that large-scale scientific studies are needed or would
be very fruitful, you know, in testing these. I don\'t know how the heck
you\'d ever do it as a matter of fact because of all the variables that
you\'ve heard this morning.

I don\'t think just the practitioner input or expert analysis alone is
going to be enough. I think the Office of Drug Safety in the Division of
Medication Error and Technical Support must have a role in this. And
they should have the final say as a matter of fact.

I\'m a little concerned that some of the things that get approved by FDA
in the divisions absolutely make no sense. You\'ve seen some of this.

And I think it has to go through people that pay attention to this, that
are doing this every day. And really have a good knowledge. They keep up
with the literature. They see the problems every day. They have the
experience. They need to be the ones that pass judgment on these
products before they\'re approved.

Label consults with ODS I think is important. Support for error
reporting and more rapid response by FDA for serious problems. We have
an awful lot of good stuff that comes through the Medication Errors
Reporting Program and the FED MedWatch Program and other programs that
are out there.

And people need to be paying attention to this, looking at it
constantly. And I know they are. But then they have to be able to react
to it. And I think they\'ve got to react a little bit quicker.

That Methergine/Brethine to me was a disaster. It\'s been five or six
years until the vials were available. And people were hurt. And it
continued and continued despite the knowledge that this was hurting
people.

I can\'t understand why it would take so long for a change like that to
be made. And I think it\'s an atrocity actually.

Support for error reporting is very, very important. Reserve color
coding for high alert drugs such as insulin, neuromuscular blockers,
concentrated electrolytes but only after testing and feedback about
prototypes.

But I have to say, this has to be used very sparingly. If it\'s going to
be used at all, only a portion of the package for the color scheme. And
it should not be associated with label information such that it draws
attention away from identifying the drug and the strength.

I would not want to see more than one product like the neuromuscular
blockers using a specific color that indicates something. And it has to
be associated, again, with education. And I think the same is true with
the other drugs as well.

It must be uniform throughout the industry and not just one company
brand although I admit I\'m not really familiar with color branding and
what the implications are.

I would hope that\'s not a situation where other companies would have to
pay a fee to the holder of the copyright or trademark, whatever it is,
and that they couldn\'t use it freely or else they couldn\'t use it at
all. That doesn\'t make any sense.

So I\'m not sure about color branding. So maybe we\'ll hear a little bit
more about that this afternoon.

Understand that actual color code schemes require simultaneous and
ongoing education of health professionals. Color code for user-applied
labels in anesthesia is well-known to anesthesia. Ophthalmics to
ophthalmologists but not by staff outside the OR. I think I made that
point earlier.

Bar-coding will help. Again, support for scientific research for the use
of color but only when it\'s one of several different variables, not by
itself in an isolated healthcare environment.

Finally, you know, there is always this question. I\'m on that Drug
Safety and Risk Management Committee and I know that questions came up
when we talked about trademarks. And is there a scientific way to study
whether or not a drug name might be problematic, et cetera.

And I guess some of the components of the tests that are being used
right now like computerization of the name and matching it with others
in the database are somewhat helpful and scientific. But keep in mind,
too, that something like this I\'m not sure if it could be completely
scientific.

I think it\'s much more related to how users react with these products
in their environment. And they\'re the experts. They are the ones that
are going to give you the good feedback.

And I\'m always reminded of this particular article which appeared in
[British Medical Journal]{.underline} a couple of years ago, which the
headline was \-- or the title \"Parachute use to prevent death and major
trauma related to gravitational challenge \-- systematic review of
randomized control trials.\" And the whole point here was obviously that
nobody has ever required a scientific study to determine whether or not
parachutes work in preventing death from free-fall yet it certainly does
work and we certainly do use it.

And then finally the article by Leape, Berwick and Bates which discusses
what practices will most improve safety. And they talk about the need
\-- for patient safety topics specifically, is evidence-based medicine
always required in order to determine what strategies need to apply?

And basically their conclusion was no. And I think this is a very
important article because they compared it to aviation safety and
anesthesia where small changes have been made all along to improve the
system. And we have had a dramatic decrease in the number of people that
have died in airplane crashes or from anesthesia incidents yet there
really haven\'t been scientific studies to support those changes.

And I think that\'s a very, very similar situation here with color
coding. I think it\'s potentially dangerous if it\'s not done very, very
carefully and reserved very, very carefully for a very small number of
products within a line. I wouldn\'t do it across a whole line.

Thank you very much.

DR. SELIGMAN: Thank you, Dr. Cohen.

Do we have questions from the panel? Wiley?

DR. CHAMBERS: Wiley Chambers. Can you give us an idea of how many colors
you think are potentially usable to distinguish? You put up a slide of
Bausch & Lomb\'s products at one point and said they all look the same.
They probably have about 300 products.

How many colors do you think could potentially be used to separate
those?

DR. COHEN: Well, I would absolutely have been against color coding the
ophthalmic products and using a color code scheme if that\'s what they
believe it to be. To me it\'s not a color code scheme.

I couldn\'t tell you what all the different colors even mean. And there
are so many. You see the problems where colors start to run into one
another and look very similar.

DR. CHAMBERS: Well, the other alternative would be that it is all black
and white. Is that what \--

DR. COHEN: I don\'t think that\'s the answer either. I heard that
comment a little bit earlier. And I would respectfully disagree that you
could still have all the labels black and white but unless you make
everything else absolutely identical \-- so in other words, if some had
different fonts, and some had different backgrounds for the strength,
and some had corporate labels, they could all be black and white.

But these are other variables. It\'s just as I\'ve shown. Whether it\'s
red or green or black, it doesn\'t matter. You\'re still going to have
the same problem.

I have seen lack of color as an effective way to prevent errors. And
I\'ll tell you how. The Baxter for many years manufactured and
distributed what they called the Baxter ATC-212 machine. And we put the
tablets and capsules in a wrapper in a machine and you would get out a
whole strip that were printed exactly the same as one another. They all
looked the same.

And the nurses became very, very aware that the only way to identify
this was to look at color \-- to look at the drug name. It was the only
way they could. And so they got used to that. But everything about those
was exactly the same. If a different manufacturer, a different size,
different fonts, et cetera, et cetera, came in, you know, it might cause
additional problems.

DR. CHAMBERS: I guess I\'m having trouble understanding. If you don\'t
think you should be using color to distinguish between then, you\'re
suggesting just the words that are used \--

DR. COHEN: Where I think color is useful is to differentiate products.
So, for example, the epinephrine vials that I showed you, I thought that
was a very effective use of color to differentiate products.

I also think that, you know, some of the manufacturers are going to have
colors for differentiating vials. They don\'t have any meaning.
Unfortunately, without practitioner testing occasionally, you\'re going
to have one vial look like another manufacturer\'s vial of something
else.

That\'s the kind of thing that I think mostly could be picked up by
practitioner testing if it is done right.

But on the other hand, I can see, you know, when you have a wide array
of colors, how that could be problematic with \-- not on the other hand,
but, you know, mixing it up with other drugs as well.

DR. CHAMBERS: Let me take a step back on \-- you talked about different
groups using the package or having to look at the labels for different
reasons. And I\'m going to come back to the area of ophthalmology. If
the patients can\'t read the label because they can\'t see well enough
to read the label, why is applying a color cap not a useful endeavor?

DR. COHEN: There are reasons. For one thing, sometimes the color caps
are removed and replaced with another color cap. So if that\'s what
they\'re going on, you could have like a green-colored cap for, I guess,
a miotic and a red-colored cap for a mydriatic and they could get
switched.

So obviously there could be a container mix-up. And we\'ve actually had
things like that that have been reported over the years.

I suppose that, you know, like I said color does have some usefulness
within the ophthalmologist\'s office and within a patient\'s home. But
it is simultaneously causing problems in the pharmacy and elsewhere.

And I think one of the reasons in this case is that you also didn\'t
take into account \-- I don\'t mean you but FDA and the manufacturers,
the way that those drug names appear. They\'re very hard to read.
There\'s a lot of words.

You could have used elevated fonts to make the drug name, for example.
The way that the company is superior. It\'s on the top of the container
above anything else. The first thing on that container should be the
drug name. The way the strengths appear within a red border.

What I\'m saying is if you gave practitioners \-- or if the company gave
practitioners and experts a chance to look at that, they could point out
these potential problems and suggest changes that would have prevented
problems with the color code scheme.

And that\'s why I said at the end I don\'t know that I could tell you
that color coding should never be used. I found it helpful with
potassium chloride. I think it would have been very helpful in
preventing neuromuscular blocker accidents and that didn\'t happen.

They\'re the only \-- that and the ophthalmics are really \-- and maybe
the dopamine are the only ones that I know of that have actually been
color coding where they indicate something. The rest of them are color
differentiation.

DR. CHAMBERS: Do you think a patient safety problem or even efficacy
problem would occur if there was a mix-up between \-- you put up
timolol, levobutanol, and betaxolol.

DR. COHEN: Yes.

DR. CHAMBERS: Would that cause any difference in patient safety?

DR. COHEN: Well, it would to the pharmacist that dispensed the wrong
thing. And that\'s the \-- see, here\'s the problem \-- and that\'s
another thing that\'s not being taken into account.

A pharmacist that dispenses the wrong medication is embarrassed at the
least because the patient comes back and tells him he has the wrong
thing. At the most, they get sued for giving them the wrong medication.

This is a very important thing to pharmacists and nurses when they make
a medication error. They could lose their job in some states. So that\'s
the kind of thing, I think, that you have to also consider when you\'re
\-- with the ophthalmic line. That actually can happen.

I mean some states are very punitive. And if an error is reported, or
three errors \-- we know that in some states, you could lose your
license.

DR. CHAMBERS: Is it \--

DR. COHEN: And in fact, there are subtle differences between these drugs
perhaps but if you take it to the extent of neuromuscular blockers,
there\'s different amounts of histamine released with these products,
there\'s different durations of activity, I mean you could have
potentially disastrous results if you mix up the neuromuscular blockers
within that same particular class if it\'s not done right.

DR. CHAMBERS: Yes, no, and I understand. And I picked that particular
example because I know those three medications have been tested against
one another and have been shown to be the same in safety and efficacy.

DR. COHEN: So you \--

DR. CHAMBERS: Now that was a particular grouping that you happened to
have up there that we have testing on.

DR. COHEN: So the ophthalmologists and possibly to the patients but not
to the people who make the errors.

DR. CHAMBERS: Right. And the question comes down to if the scheme as you
were suggesting it goes through different expert groups to go and figure
out which way to differentiate them, if there are conflicts between that
testing, in other words one may be more confusing to the pharmacists but
less confusing to the patients, or the other way around, I guess the
question is which way should the FDA be erring on?

Should they be erring on that it is more important for the patients to
be able to differentiate? Is it more important \-- the ideal situation
is that everybody can use it for their useful purposes.

DR. COHEN: Yes.

DR. CHAMBERS: But in some cases, we\'re going to run into conflicts
because we just have too many and we have to make a choice one way or
the other.

DR. COHEN: Yes.

DR. CHAMBERS: And I guess I\'m asking which way do we make that choice?

DR. COHEN: Well, I can\'t give you that answer. Again, without taking
into account \-- and I hate to repeat \-- but you possibly could use
color but not in the same way that you see it applied right now.

And not without considering the corporate dress, the logos, the fonts,
how the drug name is expressed, the strengths, three of them exactly the
same. All of that has to be taken into account.

And if you wanted to keep this color code scheme, then the rest of that
has to be redesigned because I think that\'s always going to be a
problem the way it is right now.

I\'ve talked to the ophthalmologist group, I\'ve talked to people at
FDA. And they\'re still out there. I think they could still cause a
problem.

CDR. HOLQUIST: You stated earlier that there have been some studies that
show the tall man letters have been effective.

DR. COHEN: Yes.

CDR. HOLQUIST: Are you aware of any studies that have been done to test
all these different variables like the trade dress, the color to try to
pinpoint which is the prime, you know, offender of the confusion?

DR. COHEN: No, I\'m not. Not for appearance. There is this one color
code \-- a color study right now that\'s being completed in the U.K. It
was sent to me by David Counsins from the National Health Service there.
And, you know, it\'s not published yet so unfortunately I can\'t give
you a reference but it does indicate that it\'s not going to be that
helpful to color differentiate.

But that\'s only one study. I mean there are others that need to be
done. And they only looked at the use of color itself. They didn\'t look
at all the other variables. That\'s important to recognize.

CDR. HOLQUIST: You also stated that there should be experts analysis of
this done before it comes to the Agency. Who would you envision being on
such an expert analysis from the outside?

DR. COHEN: I think it is a very similar thing to the current situation
with trademark analysis. That there are groups that do this type of
work. I suppose, you know, if a company wanted to do it, they could.

But I don\'t think an internal review like this would be useful without
working with practitioners that are actually using these products. I
think that that has to be a part of it.

So I know there are groups that do this type of testing obviously.
That\'s been going on for some time.

CDR. HOLQUIST: You spoke briefly that color coding might be helpful with
insulin drug products. And we\'ve seen a number of errors among the
insulin product line. Could you just elaborate a little bit on that,
especially when it comes to mixtures of insulin products that are coming
out now?

DR. COHEN: Well, we see a lot of errors with insulin. And it is a
problem. And some of it is due to the nomenclature. There is some
appearance similarity and the way that, again, the fonts appear on the
label.

The mix-ups for the most part seem to be with the combination insulins.
We\'re getting the 70/30, especially the ones with the very similar name
Humalog \-- I\'m sorry, NovoLog, Novolin, 70/30, 70/30. With the other
manufacturer that we see, Humulin, Humalog, one is 70/25, the other is
70/30.

Mix-ups might be \-- and I don\'t have a way to, you know,
scientifically tell you which has more errors associated with it. But we
do seem to see confusion between that.

And now we\'re seeing a whole array of new insulin products reaching the
market. It\'s very, very difficult for the practitioners to keep up with
these. I do note, however, that there has been some application of color
to some of the newer products like Lantis is a little like a light blue.
I don\'t know the exact Pantone. And I believe the Humalog product is a
red color, et cetera.

It just that it seems to be the neck of the vial, the closure, the
ferrule, and the cap. And that\'s what I meant about very sparing use of
the color.

And I\'m not sure how far beyond that would be worthwhile. There are
just so many other insulin products. And a lot of similar names. I
don\'t know. It would have to be tested.

DR. MEYER: I guess just to press that then, it sounds like what you\'re
asking \-- or what you\'re perhaps advocating there is more color
differentiation than color coding because the slide you actually \-- I
think it referred specifically to color coding of insulin.

DR. COHEN: It is color differentiation absolutely. You know again, if
you asked health care practitioners, for the most part, I bet you if you
did a little test right now, what does the light blue mean?

They wouldn\'t be able to tell you. We haven\'t done a good job
educating people. If we are color coding, we haven\'t done a good job
with educating people as to the meanings.

CDR. HOLQUIST: Yes, that was another question I had is that education,
you said, was a big component of this. How would we test to ensure that
the education was an effective campaign?

DR. COHEN: Well, it\'s very difficult. I mean it has to start at the
level of academia. People need to understand that when they\'re in
school. And we\'re not teaching that now. We don\'t even teach
medication error prevention at this point.

So, you know, practitioners come out and they go into practice, if
you\'re going to have a bunch of color coding schemes and they don\'t
know what they mean, that\'s going to cause more errors than it will
prevent them.

So I think it does start with academia. And, you know, we all have a job
to do. We reach the healthcare practitioners, you do as well. If you
were going to do it, you would have to make that part of a campaign.
Like if you were going to start color coding the insulins, for example,
nurses darn well better know what these different colors mean if you
really expect it to be color coding and not just color differentiation.

DR. SELIGMAN: Any other questions? Peter?

DR. CARSTENSEN: Dr. Cohen, you mentioned practitioner testing, I have a
background in human factors but in the device world. And I was wondering
if you could elaborate a bit on what you mean by practitioner testing.
And just to make it a little easier on you, you know \--

DR. COHEN: We\'ve done \-- at ISMP personally, we have a division called
Med Errors that does practitioner testing a lot more than I do. The
reason I would do it is if somebody reported a medication error and they
were seeking help, we don\'t charge. We will go to the nth degree to
help them to solve a problem with a medication error.

And so we have occasionally done them. We have a large database of
healthcare practitioners. Most of the list of the work that we\'ve done
has been with trademarks and not with graphics although we\'ve done some
graphics as well.

We would actually use a process, a failure mode and effects analysis
where we would actually try to set up where we believe this product
might be used based on the proposed labeling if it was a new drugs
before it was approved. We would work with the manufacturer and actually
scan the product, different presentations, et cetera.

And we would actually send it out to the field. There would be a
questionnaire where we\'d ask a number of questions about who would use
it and how this would be used and in what environment, et cetera,
besides where we thought it would be used.

And all this information would be received back after they would take a
look at the label, they could take it out to the pharmacy and look at
the shelves, all those kinds of things they would be actually directed
to do. What other products might it be stored near? You know all those
kinds of things would be asked.

All that data is received back. You would have an expert panel that does
this kind of stuff all the time actually look at these responses and
come up with recommendations that would then go back to the company.

And that could be presented to FDA, at least something there to start
with.

DR. CARSTENSEN: So it sounds like it is a controlled study. And you\'re
careful how you \-- you select a range of typical practitioners I would
\--

DR. COHEN: Correct. We\'ve long felt that this is something, along with
the trademark, practitioner input is critical to, you know, help guide
whether or not that name \--

DR. CARSTENSEN: Right.

DR. COHEN: \-- might be a problem.

DR. CARSTENSEN: Well, that\'s certainly true in the device world. We
call that usability testing \--

DR. COHEN: Yes.

DR. CARSTENSEN: \-- and validation. But it\'s a very structured kind of
testing done. It sounds like that\'s what you have in mind.

DR. COHEN: It is. You\'re under a little bit different situation,
though, that we would be in that, you know, it\'s a lot more difficult
to change things post-marketing than it would be for the drug products.

DR. CARSTENSEN: Oh, yes.

DR. COHEN: You\'re encumbered by that situation. They can\'t just change
a device because it\'s been reported as being involved in an error. They
can\'t force the manufacturer \-- you know, if they did it voluntarily,
I guess.

But, you know, if we \-- and there will be things that will get through.
I don\'t know that you\'re ever going to be \-- you\'ve heard other
speakers say that, too \-- 100 percent perfect in preventing all errors.
But when they do happen \--

DR. CARSTENSEN: Yes.

DR. COHEN: \-- you have to have a system to be constantly monitoring
that. It probably belongs in DMETS. And you need to be able to react a
little sooner. That Methergine/Brethine thing is something that we
should all be ashamed of in my mind.

DR. CARSTENSEN: I had one other question. When you mentioned FEMA, I
would put that, myself, in a larger context of risk analysis. FEMA is
just one tool \--

DR. COHEN: Oh, sure.

DR. CARSTENSEN: \-- for accomplishing that.

DR. COHEN: I tend to use that. There are about five or six methods that
could be used \--

DR. CARSTENSEN: Right.

DR. COHEN: \-- for proactive risk analysis other than FEMA. And I am
aware of that. And one technique or another would be \--

DR. CARSTENSEN: Okay.

DR. COHEN: \-- you know the technique that I\'m most familiar with is
FEMA. And it\'s worked pretty well.

DR. CARSTENSEN: Sure. And I noticed when you flashed up the ophthalmic
containers in the pastels, I don\'t know if people are aware but when
you project pastels on a screen like this \--

DR. COHEN: Right.

DR. CARSTENSEN: \-- that\'s not the true color. They tend to wash out
\--

DR. COHEN: I did mention that \--

DR. CARSTENSEN: \-- on that screen.

DR. COHEN: \-- with the \--

DR. CARSTENSEN: Did you?

DR. COHEN: \-- neuromuscular \--

DR. CARSTENSEN: Okay.

DR. COHEN: \-- blocker. Yes, that is absolutely the case. It\'s very
hard to make it look like it is.

DR. CARSTENSEN: Yes, but I think what I\'m saying is if you see it, the
same labeling in real life, there will be a clearer distinction, I
think, than what happens. What happens when you project those kinds of
\--

DR. COHEN: Yes.

DR. CARSTENSEN: \-- pastel colors, they do tend to wash out.

DR. COHEN: Yes. Thank you.

DR. SELIGMAN: Our next speaker is Dr. Mary Ann McElligott. She\'s from
the Regulatory Affairs from Novo Nordisk. Dr. McElligott?

DR. McELLIGOTT: Okay. Good morning.

I would like to begin by identifying ourselves, our company, as the
company that Carol Holquist discussed this morning. It was the company
that applied for color branding on our insulin analog products. So maybe
we precipitated this meeting, I don\'t know.

We live in a colorful world. And until 2004 when we received approval to
put a color branding color on our insulin analogs, our insulin analog
labels, as the insulin labels, were not very colorful at all.

And so what I would like to do this morning is to express our viewpoint
on the importance of the use of color on labels of the class of drugs,
the insulin and insulin analogs. And also to discuss a little bit about
how and why we feel color should be used.

There was discussions early on about color coding for insulin products
that I think some people this morning alluded to. But still we were in
2004 with no color on those insulin products. So I\'ll get into that a
little bit and also describe our experience and why we wanted to put
color on our labeling.

I\'ll also cover our proposal for using color branding on the insulin
analogs and what we discussed with FDA in trying to bring this to
approval. And also discuss a little bit about the potential risks and
benefits that we thought about for use of color in the labeling and
packaging of these insulin analogs.

So what was the history of the color for the insulin products? In the
1990s, and mainly in the latter half of the 1990s, the International
Diabetes Federation has an insulin task force that was rather active in
discussing with industry, and FDA came to the table, too, but discussing
a code for the human insulin products and also for the upcoming analogs
that were being developed, the insulin analogs that were being
developed.

Several meetings were held and out of those meetings, there was
agreement on \-- a color coding agreement for the human insulins.

And that what meant is that the agreement was for human insulin R, human
insulin N, and human insulin 70/30, each of them would have the same
color no matter what the manufacturer. So if there were several
manufacturers, R would have the same color across manufacturers.

The color coding scheme was also discussed for the analog insulins and
the first insulin analogs that were developed were the rapid-acting
insulin analogs.

The color schemes that were discussed at those early meetings in the
late 1990s were that the analogs would have their own separate colors.
So a rapid-acting analog of one company would have one color. A
rapid-acting analog of another company would have another color.
However, IDF had a whole code listing of the different colors that were
being developed.

There were no discussions on any color for the analog mixtures, which
were later developed. But there were some colors assigned for the human
insulin mixtures.

So in 2004 when we started to think about wanting color on our labels
for reasons which I\'ll get into in the next few slides, there was no
defined plan or role in ownership of the color code for insulins. IDF
was not actively hosting meetings to determine color codes for the
coming products. And industry and FDA, we were all sort of on our own.

So before I get to what we proposed for color branding, I would just
like to say the definition of color coding. However, it\'s been covered
several times before. So I will just sort of indicate how our proposal
for using a brand color on our insulin analog products is not color
coding.

So color coding is a systematic standard of an application of color to
aid in the classification and identification where a color would be
memorized to the function.

The color branding that we\'re talking about is not the systematic
standard application of color. And the color should not be memorized for
that product. It should just be an aid.

Organizational ownership of the standard code, an example with the human
insulins being discussed, IDF was going to be the organizational
ownership and the color branding that we\'re talking about, each
manufacturer would just determine on their own what color they would
want to put on their product.

Also with color coding, for it to be applied properly, there has to be
industry-wide participation and the colors need to be preassigned. And
with color branding, we\'re not talking about any such standardized code
with preassigned colors that industry would have to all participate in.

So why in 2004, by the time we got approval, was there no color on the
insulin labels and packaging? Well, early on, there were insulin
certification regulations in the CFR. And there was a special Regulation
429.12 that required that black and white packaging be applied in the
case of U-100 insulin.

So in May of 1998, there was a [Federal Register]{.underline} notice put
out. And in that [Federal Register]{.underline} notice where they were
discussing repeal of the insulin certification requirements, FDA
acknowledged the 429.12 requirement for black and white packaging and
indicated that it did have limited use.

And so by September 1998, they did indeed repeal the 21 CFR 429.12. And
so than there was no further requirement in the CFR for black and white
labeling of the insulin. So that\'s where we began our thoughts in our
company about how we could go about trying to get color on our labeling
for our insulin analogs.

So we had experience outside the United States. We sell insulin all
around the world for many years, the human insulins and the insulin
analogs. And the human insulin and the analogs all have colors, a
branding color associated with them. And there were no issues with the
use of color in selling that insulin all over the world.

So based on that experience and in the United States we had a growing
family of Novo Nordisk insulin products, we had our rapid-acting
insulin, analog-approved, and also a premixed mixture was approved, and
we had more coming on the horizon. And all of these would be looking
pretty similar with the lack of color.

So with these similarities in look, there is potential for product
confusion. And if there is product confusion, if the wrong medication
gets dispensed, safety concerns are of utmost importance. And we were
experiencing medication errors mainly at the pharmacy-dispensing level
and also package mix-ups.

So this is an example of what we were dealing with when we sought to
apply for use of a brand color on the label. On the right-hand side is
our rapid-acting analog. It\'s the packaging for a pre-filled syringe.
It\'s in a FlexPen, which is a pre-filled syringe. And on the left we
have the NovoLog Mix 70/30, which is the pre-mixed analog mixture. It\'s
also in a FlexPen pre-filled syringe.

And you also should note the similarity in brand name, NovoLog and
NovoLog Mix 70/30. In initial discussions with FDA when we were going
for approval of our pre-mixed product, we were interested in changing
the name of the product and FDA was interested in keeping the parent
name of the product in that mixture. So the names are very similar.

And not only are the names very similar, but when it\'s in our corporate
trade dress, the look of the labels are extremely similar. So you can
sort of visually see why mix-ups may be occurring.

So what we were interested in moving towards was this type of look,
which is our labeling in the rest of the world. So on the right-hand
side, we have the FlexPen pre-filled syringe labeling for our NovoLog,
which is called NovoRapid in the rest of the world. And on the left, we
have the NovoMix 30, which is our NovoLog Mix 70/30 product.

And both of them you can see are associated with a brand color. So the
NovoRapid has orange around the name and the NovoMix 30 has blue around
the name. So this was the basic corporate trade dress that we were
interested in trying to secure in the United States for our products.

And this is just an example of how color can aid in differentiating two
similar products. This is our labeling in Japan. And if you can\'t read
Japanese like I can\'t, you can still see that, you know, seeing the
color could help you match it up even if you can\'t tell, you know, what
words you are reading.

So what was our basic proposal for color branding of the insulin analogs
in our application to FDA? We basically said that we wanted to just use
color to aid in distinguishing one item from another. We did not want
this color to be a substitution for reading the actual name on the label
because that is the definitive requirement that you really need.

We were not seeking a code that would be systematically applied across
the industry to classify and identify each insulin type. We just wanted
to be able to chose a color for the brand similar to any other product
in any other class. Or even to use it to distinguish dosage strength.
And that color would be chosen and managed by each manufacturer.

And currently color is used in the industry to aid in brand and dosage
strength differentiation for many products and across many product
types.

And this is an example of in our trade dress, this is our oral
anti-diabetic agent mealtime Prandin. And we have a 2-milligram,
1-milligram, and a .5-milligram. And we use color on that labeling to
help in distinguishing these dosage strengths.

So when we were proceeding to submit an application to FDA to allow for
color on our insulin analog labeling, we thought about what were the
potential risks of using a color on the packaging.

And in the survey of the literature \-- that you really can\'t find too
much about the risks of just the use of color \-- however we did come
across discussions on \-- that the use of risks are mainly associated
with the application of color coding and drill down to the inability to
distinguish colors or the colors then become too similar that the
different dosages across the class of drugs are confused.

So the other thing that jumped out at us about color coding is it is not
proven to reduce medication errors as many people have covered this
morning. So a risk may be if several manufacturers use similar colors.

And in the case of insulin analogs, we felt that if two manufacturers
used similar colors, that use would be mitigated by the obvious
differences in the different corporate trade dress of each \-- across
the manufacturers. And also there would be differences in name. So there
would be multiple levels of ways to differentiate these products, not
just on color alone.

But one thing we did need to acknowledge was it is unknown if the use of
color branding can cause errors. And there was really no way to study
it.

So what were the potential benefits of color branding? Color
differentiation is favored by practitioners to help reduce product
selection errors within a manufacturer\'s product line. And that has
been well discussed by ISMP. However, the biggest benefit for color
branding, we felt, was the potential to reduce medication errors,
although not proven.

So what was the essence of why we were trying to get color branding on
the insulin analogs? We had insulin analog labels without color
branding. There was no color on the label to distinguish the brand. And
we had documented dispensing medication errors.

Along with these documented dispensing medication errors, we were having
an increasing number of patient safety issues. And they were associated
with this label confusion. So if the patient went home and was supposed
to get NovoLog and got NovoLog Mix 70/30 instead, with the different
pharmacologic action, there is going to be safety issues.

We had marketed Novo Nordisk insulin labeling with color in 178
countries. And some of them for many years. So we felt \-- and with
almost no issues \-- so we felt that we had a good base from which to
propose it for use in the United States.

And at the time when we submitted the supplement in 2003, there was no
prohibition in the CFR to say that you couldn\'t use color on the
insulin labels. And we did anticipate that the use of color for the
reasons summarized previously would give a favorable risk/benefit
profile for this specific issue.

And on October 8th, after many discussions with FDA and exchanges of
information, we were approved to use color on the NovoLog Mix 70/30 and
NovoLog labeling and packaging.

And this is the visual of what we ended up with. And as you can see, we
did get the use of color on the label and we also added some
differentiation in the name to help distinguish these two very similar
products. And as somebody mentioned this morning, if they\'re on the
pharmacy shelves in alphabetical order, these are definitely going to be
next to each other.

So we were very happy that we got the color on the labeling. And we
would like to express that our position on color on product packaging
for insulins and insulin analogs, we support it to aid in the
identification of insulin and insulin analogs.

And further we say that color should be proposed by each manufacturer
and approved as one variable in \-- and as a component of FDA looking at
what the trade dress looks like, distinguishing it, name, look, and
everything else that goes into looking at how a label differs from a
competitor. And what should be approved when the product is approved.

So thank you. And any questions?

DR. SELIGMAN: In looking at what you ultimately were approved to use
versus some of the earlier slides where there were much sort of bolder
graphics to distinguish them, I was curious as to why you ended up with
the latter as opposed to the former.

DR. McELLIGOTT: I think it was the basis of our negotiations. We did try
for the initial one but I think maybe with all good negotiations, you
come to somewhere in between. And that is what we ended up with. And
maybe that\'s just a first step in maybe getting to what we have in the
rest of the world to help distinguish.

But we did succeed in getting color to help aid in the differentiations.
So that\'s a good first step.

DR. SELIGMAN: Other questions? Wiley?

DR. CHAMBERS: If you do additional insulin products, are you looking to
add different colors to additional products?

DR. McELLIGOTT: Yes, with each new product coming, we would \-- when we
submit our new drug application, we would put our color proposal in
there for that product.

DR. CHAMBERS: Have you looked forward to try and plan how many colors
you think you ultimately can use and still be able to distinguish?

DR. McELLIGOTT: Well, some of the newer products wouldn\'t have the same
name. So they wouldn\'t be as confused. They would maybe be further away
on the pharmacy shelves. So we wouldn\'t necessarily have to distinguish
so carefully with each new product.

But we would just be looking to using a color just like with any other
drug product and drug brand, as you\'re developing your brand, you think
about a color that embodies your brand and you use that on your
labeling.

DR. CHAMBERS: So potentially you would use that same stripe for an
entirely different product?

DR. McELLIGOTT: Well, that would be part of the discussion since that
was the initial approval for just that stripe with the different colors.
So the third product we would have, the discussion would have to be the
color could either go as that stripe or could we then move to what we
proposed similar to the European labeling.

DR. CHAMBERS: Ultimately you believe that your European configuration is
a more distinguishable configuration than what you\'re currently using
in the United States?

DR. McELLIGOTT: It appears to us and also that\'s our trade dress all
around the world for each product, we have the same dress. And then we
use the color to help distinguish our products within our product range.

DR. CHAMBERS: have you thought of a scientific way to show that one is
necessarily better than the other? I mean you basically have the
opportunity of having two different formats. You could potentially
compare them and collect information about whether one is better than
another.

Although it\'s different parts of the world, but I\'m wondering if
you\'ve ever tried doing that kind of comparison to provide that type of
information?

DR. McELLIGOTT: Well, early on when we were proposing that we wanted to
utilize color on the labeling to help with the NovoLog/NovoLog Mix
mix-ups, we did look at our error rates in the rest of the world
compared to the United States for dispensing errors and package mix-ups.

And if you consider that we sell more in the rest of the world than
here, we had extremely rare any of those reports compared to the United
States where the reports were mounting.

CDR. HOLQUIST: Do you think that limited number of reports is attributed
to the fact that not most of the rest of the world actually collects
data on medication errors at this point in time? And that it is just
becoming a new thing in Europe?

DR. McELLIGOTT: That is one of the factors. But we did restrict it to
not way far back in history but much more current reporting numbers.

CDR. HOLQUIST: You stated that with the color branding, it\'s going to
be something that\'s company specific. What agreements do you have in
place that will help alleviate similar colors being used from another
manufacturer for the same type of drug product when they want to
introduce color branding on their products?

DR. McELLIGOTT: Well, we weren\'t suggesting that there needed to be
that kind of control over it. Just as we saw earlier this morning, that
there are several manufacturers come up with similar colors for other
type drugs.

And then when they see that it is out on the market that way, they
analyze should they change the color. And that sometimes even contact
the manufacturer and discuss changing the color. That was all we would
be interested in doing. Nothing further.

CDR. HOLQUIST: Do you have plans on introducing the IDF color scheme
into the United States for your Humulin products? And do you see that as
posing a risk for something that has a definite meaning with a
particular color to what you\'re trying to use with color branding?

DR. McELLIGOTT: Well, at this point, we haven\'t thought about the color
on the insulin labels itself. That may come in due time. But, you know,
I just can\'t comment at this time because we haven\'t made a proposal
to put the colors on those insulin products.

DR. SELIGMAN: Any more questions?

DR. CARSTENSEN: I\'d be interested in hearing \-- what you did in terms
of validating the scheme, did you use pharmacists outside your own
company to help validate your scheme?

DR. McELLIGOTT: For \-- when we \--

DR. CARSTENSEN: When you added \--

DR. McELLIGOTT: \-- developed \--

DR. CARSTENSEN: \-- color.

DR. McELLIGOTT: \-- our corporate trade dress?

DR. CARSTENSEN: Right.

DR. McELLIGOTT: We did do focus groups to see how our trade dress played
with the various customer groups.

DR. CARSTENSEN: And how do you define a focus group?

DR. McELLIGOTT: I think we had many different focus groups, the
different levels, the customers, the nurses, the doctors.

DR. CARSTENSEN: You had a bunch of people in a room simultaneously and
you queried them? Is that what you mean by a focus group?

DR. McELLIGOTT: I don\'t remember how the \-- I think our trade dress
has been in play about three or four years and I don\'t remember how we
went about doing the focus groups exactly.

But I do remember that as the new look was being developed, there were
definite focus groups to see which new look \-- how the new look played
against other looks. And that\'s why this look was selected.

DR. CARSTENSEN: Okay.

DR. SELIGMAN: Thank you very much.

CDR. HOLQUIST: When you showed your slide with the insulin pen, both the
pens were actually blue in color and the color at the tip were the only
like differentiating factors.

Have you experienced, like they do in the ophthalmologic world where
patients will just refer to the color of like the pen that they\'re
using? Like I use the blue insulin pen?

And if so, do you envision if another company uses that particular color
for some other branding, do you anticipate confusion among different
product lines that use the same type of device?

DR. McELLIGOTT: Are you saying that the people are confusing the navy
blue of the pen or the color of the \--

CDR. HOLQUIST: The navy blue of the pen because often times those things
will be taken out of the carton that has more color on it and they\'ll
just rely on what\'s on the actual container label, which would be the
pen in that case.

DR. McELLIGOTT: Yes, well I think on the pen label, as I showed with
that stripe on the outside of the box, that stripe is also on the label
on the pen. Right.

DR. SELIGMAN: Thank you very much.

DR. McELLIGOTT: Thank you.

DR. SELIGMAN: Our next speaker is Dr. Joseph Cranston from the American
Medication Association. Dr. Cranston?

DR. CRANSTON: Good morning. My name is Joseph Cranston. And I\'m a
pharmacologist by training. And I currently serve as the Director of
Science, Research, and Technology at the American Medical Association.
And I\'m speaking here today at this Part 15 hearing as an official
representative of the AMA.

First of all, the AMA commends the FDA for holding this hearing to
determine the benefits and potential drawbacks of applying color to drug
packaging and labeling as a means to identify, classify, or
differentiate drug products, and to prevent medication errors.

The AMA\'s Council on Scientific Affairs, hereafter to be referred to as
the Council, presented a report at the AMA\'s annual meeting in June
2004 titled \"The Role of Color Coding in Medication Error Reduction.\"

The recommendations of that report were adopted by our House of
Delegates, which is our policymaking body. I was the staff author of the
report.

The FDA cited this Council report in the [Federal Register]{.underline}
notice for today\'s meeting. And my comments today will discuss the
major findings of the report and its recommendations.

The Council report only addresses color coding, which has been defined
earlier today and in our report we use the ISMP definition as the
systematic standard application of a color system to aid in the
classification and identification of drug products. A color coding
system allows people to memorize a color and match it to its function.

The Council report evaluates current evidence on whether color coding
reduces medication errors. The report includes results of a literature
review and discussions with experts in the field.

The Council found that currently there are three widely-used color
coding systems for pharmaceutical products that are intended to reduce
medication errors.

First, as already mentioned today, the USP black-cap packaging
requirements for potassium chloride for injection concentrate.

Second, also as already mentioned today, the American Academy of
Ophthalmology\'s uniform color coding system for caps and labels of
commercially-available topical ocular medications, a color coding system
that is supported by the FDA, at least in one of its Agency guidance
documents.

And thirdly, the ASTM Standard D4774-94 for color coding of user
applied, not commercially available, user-applied syringe labels in
anesthesiology. This ASTM standard, which is supported by the
anesthesiology community, assigns a specific color to each class of
anesthetic drugs. For example, induction agents.

Anesthesiologists affix the appropriate colored labels to syringes
containing the appropriate medication prior to surgery. These
user-applied color labels on syringes are intended to provide visual
queues during surgery so there will be a reduced risk of inter-class
drug errors due to accidental syringe swapping.

Each of these color coding systems appears to enjoy strong support from
health professionals such as ophthalmologists and anesthesiologists.
However, based on the Council\'s literature review, published scientific
evidence that shows that color coding reduces medication errors is
extremely limited. And for the most part, anecdotal.

Based on volunteer reports to the UPS-ISMP Medication Error Reporting
Program, elimination of fatalities due to mix-ups between sodium
chloride 0.9 percent injection and potassium chloride for injection
concentrate were observed after black caps were required on the vials of
the latter product. This observation suggested the color coding had a
positive effect on reducing medication errors with these products.

However, deaths due to accidental concentrated potassium chloride
injections still occur. Thus medication safety experts such as the ISMP
also recommend restricting the availability of potassium chloride for
injection concentrate products in clinical areas.

Prior to the implementation of the AAO\'s color coding system for
commercially-available topical ophthalmics, there were documented cases
of serious adverse events resulting from patient difficulty in
distinguishing between various ocular medications.

However, the Council could not identify any published scientific studies
that evaluated whether this color coding system has led to a reduction
in medication errors.

On the other hand, as Dr. Cohen already pointed out this morning, the
USP-ISMP Medication Error Reporting Program has received reports of
intra-class medication errors with topical ocular medications. For
example, mix-ups between cyclopentolate hydrochloride 1 percent and
tropicamide 1 percent solutions have been reported.

And as Mike suggested earlier today, while the AAO\'s color coding
system may work well in physician offices and in patients\' homes, the
potential for error could increase in pharmacies and in nursing units
where product packages with similar colors, logos, fonts, and sizes are
placed next to one another.

The Council identified one reasonably well designed scientific study
that attempted to determine whether the color coding system for
user-applied syringe drug labels in anesthesiology actually reduces
medication errors. Fasting and Gisvold analyzed inter-operative problems
related to anesthesia, including medication errors, that were
prospectively recorded for over 55,000 procedures during a 36-month
period in a 970-bed hospital in Norway.

After the first 18 months, the anesthesiology department implemented
color-coded syringe labels according to ASTM Standard D4774-94 and also
had educational meetings and audits that focused on medication errors.

The investigators observed a 37 percent decrease in medication errors
after the intervention. However, this was not statistically significant
because the total number of medication errors in the study was extremely
small, about 0.1 percent. Also, differences in the number of syringe
swaps before and after the introduction of color-coded syringes was not
statistically significant.

The authors concluded that syringe swaps were not eliminated by color
coding and suggested color alone may not be sufficiently strong as a
visual queue to eliminate errors.

Thus, based on the Council\'s literature review, there clearly is a lack
of published evidence that proves color coding reduces medication
errors.

The Council also contacted individual experts from a number of key
organizations involved in medication error prevention, including the
American Society of Health System Pharmacists, the ISMP, USP, FDA, and
PhRMA.

All recommended caution in the application of color coding systems in
some organizations. As was pointed out by Dr. Myers earlier today, the
AHP opposes reliance on color coding to identify drug products.

Some of the potential problems with color coding that were identified
included the following. And some of these have already been shown today.

There\'s a limit in the number of discernible colors available for
commercial use.

Subtle distinctions in color are poorly discernible unless products are
truly adjacent to one another.

As previously noted, color coding of drug classes can increase the
chance of intra-class medication errors.

Colors may fade when exposed to light.

It is not always possible to exactly reproduce Pantone colors from batch
to batch.

Approximately eight percent of men and less than one percent of women
have some difficulty with color vision.

Color coding can be error-prone if it is not applied consistently across
the industry or within a single manufacturer\'s product line.

Physician and other health professionals may be unable to remember large
or multiple color coding systems.

And finally, color coding may offer a false sense of security and in
some instances, result in failure of the physician or other health
professionals to, in fact, read the label.

So based on its literature review and discussions with experts in the
field, the Council put forth two key recommendations in its report that
were adopted by the AMA\'s House of Delegates.

First, the AMA recommends that the FDA, and the USP, and the
pharmaceutical industry that color coding of commercially-available
pharmaceutical products for the purpose of preventing medication errors
be considered cautiously and on a case-by-case basis.

And secondly, the AMA encourages further research on the effectiveness
or lack thereof of color coding of pharmaceutical products to reduce
medication errors.

Thank you.

DR. SELIGMAN: Thank you, Dr. Cranston.

Do we have any questions? Members of the panel?

DR. CHAMBERS: Wiley Chambers. Does the AMA have suggestions on how the
research would be conducted?

DR. CRANSTON: No, frankly.

(Laughter.)

DR. CRANSTON: On a personal note, I mean I would agree with Dr. Cohen
that the more important thing, I think, is at least with color
differentiation and even with color coding is to do the studies up
front, you know, failure mode and effects analysis and so forth, to
ensure before the product is ever marketed, you know, that there is some
comfort that what\'s been selected is going to work.

DR. CHAMBERS: I think the question comes down to there are a number of
different constituent groups and there\'s no immediately obvious way to
conduct that either prior to or after approval. And there is \-- if
there are conflicting results between the different groups, deciding
which groups carries more weight is not an easy thing.

DR. CRANSTON: I appreciate your problem.

(Laughter.)

DR. CRANSTON: I don\'t know how to solve it. I mean we may get calls
tomorrow, you know, from the ophthalmologists and the anesthesiologists
that they didn\'t like our presentation. I mean this is the evidence we
came up with.

DR. CHAMBERS: Thank you.

DR. SELIGMAN: Thank you very much, Dr. Cranston.

Our next presenter is Dr. James Broselow. Dr. Broselow, are you here? If
he is not, we\'ll move on to the next presentation and come back to Dr.
Broselow when he returns.

Dr. Frank Kyle from the American Dental Association. And I believe I
have your presentation here.

DR. KYLE: Thank you.

My name is Frank Kyle. I\'m a dentist. I work for the American Dental
Association in the Washington, D.C. office. I\'m a Manager of
Legislative and Regulatory Affairs.

And I\'m here this morning representing our Council on Scientific
Affairs, pretty much at the invitation of the Food and Drug
Administration, to talk about our limited experience with color coding
for dental anesthetic cartridges.

I think if any of you have been to a dental office, you\'re very
familiar with the dental anesthetic cartridge. I think it is a fairly
unique delivery system for dentistry. I\'m not sure of other
practitioners that use that particular mode of administering anesthetic.

Let me just say a little bit about the American Dental Association to
start with and our Seal of Acceptance. The ADA is a member organization.
It has about 152,000 members. That represents about 72 percent of the
dentists in the United States.

We have long sought to promote dental product safety and effectiveness
and our Seal of Acceptance has become well recognized among consumers
and the dental professionals as a measure of that safety and
effectiveness.

We \-- the ADA that is \-- issued the first Seal of Acceptance in 1931.
It is strictly voluntary, however, there are more than 300 countries
that participate in the Seal Program. There are about 1,100 products
that carry the Seal of Acceptance. And I\'m sure if you\'ve been to any
grocery store or pharmacy, you\'ve seen the Seal on toothpaste,
mouthwashes, et cetera.

About 40 percent of the Seal of Acceptance programs are consumer
products such as toothpaste and so on. The rest are, of course,
materials that are basically marketed or provided to the profession such
as restoratives, antibiotics, and dental anesthetic cartridges.

In the early 1990s, the ADA House of Delegates, again our governing
body, passed several resolutions directing that the Association help
develop a uniform color coding system for local anesthetic cartridges.

The idea behind this was to provide an extra safety factor complementing
the need to read the cartridge label, which could be difficult because
of the size. I\'m sure you\'re familiar with that small 1.0 cc
cartridge. Furthermore, it was found that in some instances, the
cartridge label could become worn off from handling.

So to further this process, the Council on Scientific Affairs held
several meetings with manufacturers of ADA-accepted local anesthetics to
develop and finalize a code. In addition, there is a Standards Committee
on dental products that provided input into this process.

The manufacturers, in general, were very supportive of the ADA\'s
efforts in developing the color coding system due to their concern about
possible confusion due to conflicting color schemes and agreed on a
format for a color code: a color band a specific distance from the
plunger-end of the cartridge, black lettering for all labeling on the
cartridge, and a time period for implementation.

This is basically the color code scheme or the labeling scheme that is
used on the dental cartridges. As you can see, there is a color code
band specified a specific distance from the end. There is a specific
color scheme given to the particular type of anesthetic and I\'ll show
you that in just a moment.

There\'s the stopper \-- the stopper is an orange rubber stopper and
it\'s not designed to be used as an indicator of color code. The
lettering is spelled out. And it should be durable so that it is not
easily worn off in handling.

Basically there are three types of lidocaine that are used in dentistry.
And these are the three color codes that are assigned to the lidocaine.
A couple of mepivacaine concentrations that are commonly used. A couple
of prilocaine concentrations that are commonly used. And then two other
additional long-lasting anesthetics that are frequently used.

The color coding format, as agreed to by manufacturers, was approved by
the Council on Scientific Affairs in 2002. And became part of our ADA
Seal Program in 2003. So we just have a few years experience with it.

All of the participants, that is, manufacturing participants in the ADA
Seal Program currently comply with this system. That includes about 80
percent of the market for local anesthetic in the United States.

The Association is not aware of any reports of error as the result of
the implementation of this color code system. I must say, however, that
I don\'t know that the Association had any particular experience with
error reporting prior to the initiation of this color coding system.

And finally, the ADA color coding system has been presented to the ISO
for inclusion as an international standard for dental and local
anesthetics and that was done in 2003.

And that completes my comments.

DR. SELIGMAN: Thank you, Dr. Kyle.

Any questions, comments from the panel?

Carol?

CDR. HOLQUIST: Just one comment. We actually did get a report of
confusion of someone picking out the wrong syringe. And I think it was
the blue color that\'s used for the mepivacaine because it\'s like two
blues that you use in that same color scheme.

I don\'t think it was administered to the patient. It was caught prior
to administration.

DR. KYLE: Again, I don\'t know that we would necessarily get that kind
of information. You would probably be the recipient of that information
more than we would be.

Let me just also add \-- I forgot to mention in my comments that one
side effect, if you will, or one benefit of this system is it does
assist the support staff of the dentist to order cartridges. Like they
can easily when they\'re running low on a particular concentration or
branding or whatever that they might want to keep in supply.

DR. CHAMBERS: Does the ADA have any plans to either conduct a response
or any kind of testing to look at the utility of this system?

DR. KYLE: None that I am aware of.

CDR. HOLQUIST: And do you foresee the introduction of many other
products within that color scheme?

DR. KYLE: You know that\'s a good question. And I\'m afraid I don\'t
know the answer to that. I would basically assume that these were the
products in place in the early 2000s when the system was put into place.
I don\'t know of any new advances in local anesthetic.

My guess is that if such a new product were developed, they would again
meet with the standards group and determine a color code for that new
class or new category of anesthetic. But I\'m not aware of any that have
been introduced. And I don\'t know exactly the procedure that will be
done.

CDR. HOLQUIST: In your practice setting, is it that all of these
cartridges are just laid out on the tray? Or are they already loaded
into the \--

DR. KYLE: In my experience, and I suspect this is true for most
practitioners, they have a limited assortment. They wouldn\'t
necessarily have all eight or ten in their own offices. They would have
their favorite ones, probably two or three maybe with some short-acting
and some long-acting and that sort of thing.

Generally speaking, depending on the procedure set up for that or that
patient\'s particular treatment diagnosis, they would know whether they
would want a short-, or a medium-, or a long-acting anesthetic.

And probably the doctor\'s preference is well known to the assistant and
she just puts \-- he or she puts out the cartridge appropriate to that,
maybe a couple of them, that sort of thing.

So there\'s probably only one or two on the treatment tray at any given
time. If you needed, you know again, for instance an oral surgery
procedure, they might do moderately acting anesthetic to start the
procedure, to do say the extraction, and then give a long-acting
anesthetic at the end of the procedure to tide the patient over until
the full effect of their analgesics might kick in.

So there might be two different ones. But you wouldn\'t have probably
more than a couple on a tray at any one time.

DR. CHAMBERS: Are there any other color schemes used for any other ADA
\--

DR. KYLE: None that I\'m aware of. And none that the Council of
Scientific Affairs identified for me.

DR. CHAMBERS: Okay. And I take it from your earlier statement, there are
no plans to expand beyond the anesthetic?

DR. KYLE: None that I\'m aware of. Again, this is \-- we\'re very much a
provider-driven organization. So if the dentists came to us and said we
would really like to see a restorative material color system, then they
would probably take a look at that. But I don\'t think there are any
plans to do that.

DR. CHAMBERS: Thank you.

DR. SELIGMAN: Thank you, Dr. Kyle.

Dr. Jensen, Dr. Allan Jensen from the American Academy of Ophthalmology.

DR. JENSEN: Thanks. Thank you very much. I am Allan Jensen. I\'m a
practicing ophthalmologist. I actually see patients in the City of
Baltimore. And I\'m past President of the American Academy of
Ophthalmology. And I appreciate all of the previous references. We also
appreciate the invitation to address the hearing.

A number of points, first of all, we\'ve been successfully using a color
coding system for over 20 years. We have no science to prove that it is
helpful. We do think it\'s been a safety feature for our patients and
for our doctors. But again, we have no science and I don\'t know of any
scientific studies that show that.

I would like to agree with the previous speakers that color coding is
not the major answer. It is certainly necessary to read the label.

And as someone seeing patients mostly of Medicare age, some with poor
vision, I certainly agree, again, that we should have large labels
although it is hard to put a large label on an eyedrop bottle. We should
use good contrast. Black and white is much better than gray on maroon or
maroon on gray. And there should be some uniformity in the labeling of
these drugs.

In ophthalmology, we are unique because all the drops look the same. We
don\'t have different colored pills and different shaped pills. All the
drops are tiny and round and either clear or usually white.

We continue to endorse a system \-- a uniform color coding system for
topical ocular medications, again, as we have for over 20 years. Many of
our patients are partially sighted and elderly. And they are especially
susceptible to accidental installation of the incorrect eyedrops. The
uniform color coding system will help patients and doctors distinguish
amongst eye medications.

You should be aware, and I know you are, many of our patients after
surgery are taking three or four different drops. And to be perfectly
honest, they don\'t say I\'m taking my Ocuflox and my prednisolone, and
my levalbuterol.

They say \-- and we ask are you taking the tan drop and the red drop and
the pink drop. And even very intelligent patients, if they\'re only
taking them for three or four weeks, find it much more easy to talk
about the color of the bottle rather than the exact name of the drop.

And when I start my practice each day, I have five or six bottles lined
up. And some are dilating drops. Some are anesthetics. Some are glaucoma
drops. And I\'ll certainly identify them at the beginning of the day.

But when I see 30 patients a day, I don\'t look at the label each time I
put the drop in. I\'ve done that at the beginning of the day. And after
that, I identify them by the color of the bottle.

This system was originally initiated after we, at the Academy, received
reports and we received reports from the National Registry of
Ocular-Induced Drug Side Effects, saying that there indeed had been
errors because people had confused their medications.

And we\'ve developed this system in cooperation not only with the FDA
but with the pharmaceutical industry, which has been very helpful.
Twenty years ago, it was one of my first jobs in the Academy.

And one of the things I learned, interestingly, it\'s very expensive for
the drug companies to put these tints on the bottles and on the caps.
They have to make sure they\'re not toxic. Have to make sure they don\'t
degrade the drug and so forth.

We chose the colors and some of this is lost in history. I don\'t know
why we used red for one and green for others. But we choose them by
classes of drugs, not by exact drugs, which we\'ll talk about a little
later, but according to the nature of the disease, the produce side
effect profile, and the risk of serious sequella if they should be mixed
up.

As I say, we\'ve done this in cooperation with the pharmaceutical
industry. And we still work with them. We certainly will not have 100
percent consensus because of limited colors. And this system has been
based upon primarily patient safety, prescribing patterns, and the
available color options.

Here is indeed our system. And I would like to respond a bit to Dr.
Cohen\'s remarks. When he did show the three drops all with yellow tops
with different names, the fact is they were all the same class of drugs.
They were beta-blockers.

The color of the cap, the color of the bottle is not meant to tell
exactly what the name of the drug is but it is to tell which class it is
in. And you still do indeed have to read the label.

Likewise, when he was throwing out Bausch & Lomb bottles that looked
similar in color, the fact is they were all antibiotics. And they all
were the same color tan because they were antibiotics. And the purpose
is not to identify the precise drug but just the class of drug. And it
certainly is true there can be intra-class errors.

It was mentioned on the slides the colors got washed out. So I actually
brought some real examples. And the red is for dilating drops or
cycloplegics. Orange is carbonic anhydrase inhibitors. Green are
miotics. And that can be pilocarpine or it could be carbachol. We don\'t
know. You have to read the label.

One of the points that was also brought out was that the labels can be
\-- or the tops can be mixed up. And I certainly agree.

Our policy just says that top and the label should be the same color.
It\'s very helpful, though, and this company has done it, that also the
top of the bottle be colored. So if you do mix up that cap, the patient
can still tell the difference. Not all companies do that.

So I would say if you are going to have a policy or change the policy,
besides having the cap and the label be color coded, the top of the
bottle should also be color coded.

We do have the two ongoing concerns. Number one, as we see more and more
generics, they\'re not all following the rules. And I get some drops now
that all have white tops and white labels. And indeed those I do have to
read the label every time I use it. And it makes it a little difficult
for me and the patient.

To me one of the most major problems we have is not color coding but \--
and this was mentioned also before \-- we see a lot of accidents, once a
week in the emergency room, patients who have non-drugs, we talked about
guaiac testing materials, we see the glue, we see Super Glue in bottles
that look exactly like eyedrops. And I don\'t know who should regulate
that.

But I think a major problem we should try to address is how to avoid
confusion for the patients when non-ophthalmological are put in bottles
that just look like eyedrops and cause significant injury.

In summary, the Academy of Ophthalmology continues to recommend this
uniform color-coding system for the caps, labels, and ideally the bottle
tops of all topical ocular medications. We don\'t have science. But it
has been very useful to us. And we think it has been a safety measure
for our patients.

I\'m certainly glad to answer any questions.

DR. SELIGMAN: Thank you, Dr. Jensen.

Any questions from members of the panel?

CDR. HOLQUIST: You mentioned that within a product class, like within
the same class, errors wouldn\'t necessarily be a problem for you. What
about if somebody had an allergy to one of the antibiotics or there was
like a steroid used in one of the combinations, do you see a lot of that
type of confusion? Or is it just \--

DR. JENSEN: Well, certainly if it\'s in the antibiotic class, people can
be allergic to one antibiotic and not another. You have to take the
history and look at the label. The color coding is not to eliminate
that. It\'s just so you know if it is an antibiotic.

And you\'re right. It becomes very complicated when people have
combination drugs. There are drugs that are a combination of
antibiotics, steroids, and frankly I don\'t know how we code those. It
does become a problem.

Dr. Chambers may know the answer to some of those things.

CDR. HOLQUIST: Are you running out of colors?

DR. JENSEN: Yes.

(Laughter.)

DR. MEYER: Who do you see as the primary target for this color? For your
particular color coding? Is it for the patients? Is it for the
practitioner? Presumably not so much the pharmacists.

DR. JENSEN: I was interested in the discussion that the pharmacists
might be confused about the colors and give the wrong drug. Now the
pharmacists job is to read the label and give out the right drug no
matter what the color is.

Number one, it is for the patient. We have 80-year-old patients who have
bad vision, who are getting feeble, and it\'s hard for them to
recognize. I think it helps them tremendously to have a color on the top
of their bottle. And clearly it helps us, too.

DR. CHAMBERS: This is Wiley Chambers. Let me just make \-- take the
opportunity to make one comment. The slide that was shown with the
combination steroid/anti-infective are not following the scheme.

The steroid/anti-infective combinations are approved as steroids. They
have labels that say they are for steroid indications. And they are
supposed to have pink caps. They were not supposed to have tan caps.
That\'s an error with the manufacturer. That\'s not reflective of the
color coding system.

DR. JENSEN: Thanks. Thank you.

DR. SELIGMAN: Thank you, Dr. Jensen.

Has Dr. Broselow arrived yet?

Why don\'t we take a few minutes then and ask if there are any questions
or comments from members of the audience, either for any of the speakers
or anything that anyone would like to add or say.

We\'re going to give Dr. Broselow another 15 or 20 minutes to show up
since we were ahead of schedule.

Are there any comments? Thoughts? Questions? Anecdotes? Good stories?

Yes, sir? Please identify yourself.

MR. NEWMAN: Yes, Rick Newman, R&D Services.

Just a thought, you know, as I\'m searching for consensus and seeing
where folks are going with all of this and trying to understand some of
the next steps, it seems like color coding in one specific area that,
especially with user applied or in the ophthalmic situation, but then as
I look at the area of color differentiation, using differentiation,
which a lot of people are using both from a manufacturing standpoint,
it\'s starting to be used by some pharmacy compounders for use in
hospitals when there are specific needs and issues.

And I got to thinking that really it\'s almost like talking about what
we use for a highlighter, with a highlighter pen when we\'re looking at
our notes or reading a book. That if we highlight the key information,
as Dr. Cohen was talking about, for the dosage or the strength, and just
use it to highlight those key points that we want to be sure we get
across to whoever might be using the product, that might be a good way
to look at the limited use of color. Just a thought.

DR. SELIGMAN: I think that would probably fall in sort of the class of
what we call differentiation, I presume, highlight.

Any other comments from members of the audience? Any questions for the
speakers?

Mary, do we have any information or status on the one remaining speaker?
Okay. Well, our final speaker is coming from some distance. So he may be
stuck.

So I think what we\'ll do then, if you don\'t mind, rather than keep you
all waiting, is let\'s take a 30-minute break. We\'ll reconvene at 12:15
when he is scheduled to speak. And hopefully he\'ll be here. And that
will be the final presentation.

So let\'s all take a 30-minute break then, okay?

(Whereupon, the foregoing matter went off the record at 11:43 a.m. and
went back on the record at 12:14 p.m.)

DR. SELIGMAN: Our final speaker has indeed arrived. So Mary if you just
grab folks. For any of you who has ever come from a large family, I\'m
sure you\'ll be very interested in this one, \"Color Coding Kids.\" I
never could figure out how my mom kept all of us apart. So please be
seated and we\'ll begin in just a moment.

Our final speaker of this morning is Dr. James Broselow. Dr. Broselow?

DR. BROSELOW: Thank you very much. It\'s a pleasure to be here. And I\'m
sorry I was late. I went to an awful lot of trouble to be late. I got up
at five o\'clock in North Carolina.

Anyway, this is called Color Coding Kids. And when I say we, it\'s Dr.
Bob Luten, I\'ve worked with Dr. Luten since back in the 80s. And I\'m
going to give you a little bit of background on this idea so it won\'t
look like it\'s coming out of the middle of nowhere.

This is me and this is \-- that\'s my claim to fame. That\'s the
Broselow Tape. And it\'s a length-based device. I was in family practice
in Frankenmuth, Michigan, and I moved to Hickory, North Carolina, and I
switched over to emergency medicine.

And when I did that, I started moonlighting in emergency department and
go fairly comfortable with adults but recognized fairly early on that in
a rural ER in the United States, when children came in, it was a
nightmare.

First of all, everything was size related, all their equipment, their
drug dosages. You\'d have to look at the child, guess their weight. A
lot of times they were unconscious or in a lot of distress. They
couldn\'t move or talk. So you didn\'t really know how big they were.
Sometimes you didn\'t have an age.

Then you had to estimate from your estimate of their age what their
weight was. Using a complex formula, you\'d come up with a weight
estimation. You would try and round it out to kilograms.

Then you would start to try to pull from memory or a card all the doses
of the various drugs that were nightmarishly close, milligrams of
atrophine .1, so-and-so .01, so-and-so .2. And you were doing all these
drug dosing and then telling the nurse the dose. If you happened to
figure out, they didn\'t know if it was correct. And then they would
have to translate that to mLs, of course, to give it to the patient.

Meanwhile, you were treating things that people never saw, rare
emergencies. Everybody was nervous. You couldn\'t find the equipment.
And so it was really a mess.

And I had the idea to get something more objective. And so I did some
studies of just rural North Carolina on the relationship between
children\'s length and their weight. And as you would guess, length was
a good predictor of weight. And we knew it would work.

We didn\'t know if it was close enough to be useful but the studies that
I did did show a good correlation. It was repeated by the group that put
the PALS course together. And they did a national study. And it showed
that length was the best predictor of weight.

Well, once you had this relationship here with weight and length, you
can make little kilogram boxes. And in those boxes were calculated the
dosage of all those drugs. So you were actually measuring the dose from
the child. It was a direct measurement.

And so this has been well accepted. Once we started looking at length
and weight, it was interesting to look at what else might correlate with
length.

And I was most interested in equipment because the pediatric equipment
for resuscitation was very critical, especially the endotracheal tubes
so that they would fit snugly because you can\'t blow them up and make
them fit like you can an adult\'s that have balloons on them.

So a number of studies were done in some children\'s hospitals and other
hospitals\' operating suite, and it showed that length was the best
predictor of endotracheal tube sizes.

Well, once we had those critical pieces of equipment, we related the
other equipment for children and put them in length zones. And so this
little part of the tape over here that is colored had the name of about
20 pieces of equipment. Well, we thought if we color coded it, you
wouldn\'t have to read all the equipment.

And it led to a storage system in which you could measure a child, get
their length, and then you could open a drawer like this crash cart that
has color-coded equipment that matches. Or you could just store your own
equipment by color. But it was a way of getting the proper size
equipment.

This is just another way of doing this. This is a soft bag. This is
velcroed off so in a hospital, if the child were a purple, you could
take that purple bag off that has their critical equipment and send them
in the stretcher if they go to Trauma for a CT. And also that, you know,
could by used by EMS. It rolls up.

So that was a system that we developed. This is just to show you a time
frame. These worried-looking guys are EMTs. That\'s a Broselow Tape.
That\'s that bag I showed you.

This is Dunblane, Scotland, in one of those early tragedies when a crazy
person came in and shot a bunch of children in the same classroom. They
had just put the system in. This says yellow boxes were lifesavers. Why
were they yellow? Because most of the kids were the same size because
they were in the same class.

So what I\'m showing this for is to show that this has been fairly
widely used and also it wasn\'t just me in a rural ER in North Carolina
that had a problem. I had addressed pretty much a universal problem with
children in the sizing issue.

And when I tell this story \-- I\'m going to get into the system but my
daughter is getting her Ph.D. in German literature next month. She
can\'t do math. She had no interest in medicine. But when she was about
15 years old, she could take a \"Broselow Tape\" and come up with the
dose of every drug for a pediatric emergency, every piece of equipment,
and she had no medical training.

So the implications were if I could take one of the hardest things for
me to learn as a physician and take it so my daughter could do it, there
were strong implications in that.

So Dr. Luten and I have spent a long period of time trying to develop a
system related on those concepts. And, you know, basically what we want
to do, we call this Color Coding Kids but what we want to do is we want
to color code kilograms. And we want to put them into zones because
medications have ranges.

As you all know, amoxicillin 500, 50 to 100 is the range. So a drug has
a range. So we revised the ranges so the color ranges were within the
therapeutic ranges of drugs. And with that in mind, we could actually
have a universal system.

Now you could call the range 2-3, like 2-3 kilograms, 4, 5, 6, 7, 8, 9,
but they\'re numbers. They\'re confusing because milligrams are numbers,
mLs are numbers, weight is a number, the time is a number. So we wanted
to call the zones something different.

So what you could think well, let\'s call them a name. You could call
them an apple and a pear and a peach. We elected to call them a color.
Why do I mean call them a color? Because if somebody called an emergency
department and measured a kid and got their length color, they could say
their color is blue. But you don\'t see the color blue, right? It\'s a
word that indexes a zone.

But also because it is color coded, you can see it. So it has that added
dimension on top of the name.

So this is just to show some information that this has become widely
accepted. It\'s in PALS and Apples and most of the major textbooks
because length was the best predictor of weight.

Interestingly, it does a couple things. One, is it predicts weight
because it\'s the best predictor and we have a bunch of studies. Two, it
defines ideal body weight in the sense that many acute drugs just go
into the water part of the body anyway. So it\'s not a bad place to
start. And third, it\'s the best correlation with equipment which
you\'re doing at the same time.

Now we talked about length, but this is clearly a weight-based system in
the sense if you want to color code a child and you know that they\'re
41 to 51 pounds or 19 to 23 kilograms, you have a weight. There\'s no
reason to length them to get the weight. So they would be a blue.

But we had the added feature that if you don\'t have a weight, you can
always get in your information system. You can get a color that gets you
into your tools.

So in this scenario, it\'s a \"Broselow Tape\" with nothing written on
it. Picture a carpenter\'s tape, or later we\'ll show you a wall chart,
but it\'s the relationship between length, lean body mass, and weight.
So it indexes a system.

I\'m not going to go into this but we\'re building a hospital system and
a system for physicians and people that treat children. And the easiest
way to see how this would work is this is a pocket book. That\'s the
weight range.

So in this scenario, you go to that section of the book. You\'re in the
blue section. And everything is related to those weights in kilograms.
And it shows you \-- we can do analgesics and antibiotics. And you\'ll
see that there are a bunch of antibiotics.

We tend to use keywords to identify these zones like we call this
amoxicillin high dose. The dose is 12 mLs every 12 hours. So it really
just calculates for you. But it takes care of size-related things. If
the kid is a blue, then we know what size of cefaclor we want to use
because we know his size. So we can give some recommendations.

And I can go into this later. I\'m not really going to go into the
system. But we\'re trying to do is develop a system for hospitals that
reduces errors.

In this scenario, these doses tend to be the dose the doctor would order
like milligrams or mLs. In our hospital system, we\'re trying to get the
color actually to give the dose in mLs, what the nurse would pull out at
the scene.

An example of how we could do this \-- and this gets more related to
labeling, this is what I call a mLs rainbow. It\'s for epinephrine. The
one on the left is the 1/10,000 concentration. The one on the right is
1/1,000.

Now what could you do with that label? Well, if you take that one on the
right and you put it on that box of epinephrine, then your Broselow
pull-out tape, your color, or the weight color tells you the mLs that
you pull out of the bottle.

See, all the steps are eliminated. You go directly from your thought
process to what you want to give the child. When you think of how many
steps people go through to calculate, to estimate, and then they can
make errors in any of those stages but some of the bigger errors are
time delays and also that people get very nervous, especially if you\'re
working with a team.

In a way, this is very similar to amps in adults. You know the old amp
thing where you open an amp, you screw it in, and you give it. Well, in
kids, we don\'t want to be cute and put every medicine in an amp. But we
want to put information in amps.

In other words, once you know the child is a blue, then what you want to
perform here is you just go into the color.

You\'ll notice in our system that we never give a color without the
name. So that\'s how we handle color blind. People have asked us that.
It will be a fixed sequence. But also we always have the name.

This is over-the-counter medications and the approach to that. Again,
it\'s a weight-based system. We would recommend that people use weights
if they have it to get the color. But this is the idea of a wall chart
to get the color. So you get into a color information system.

Now this is an example of how a color, a length color, could relate to a
line on a syringe. Now you\'ll notice that you don\'t really have to
speak much English to do that, do you, once you kind of understand how
it works.

If you know your child\'s color or weight, then you use that color to go
directly to the syringe. If you don\'t, you can length them and use a
wall chart.

And why would you want to use length for over-the-counter medicines?
Well, weight is fine. But if you want a safety system, think about
length. It\'s almost impossible to overdose anybody by length. Any
normal child.

Now how can I say that? Well, first of all, if the child is normal, the
length predicts their ideal body weight. So it\'s the right color. If
the child is obese, a lot of us don\'t necessarily want to dose the
heavy dose. So this is less. You\'re not going to overdose anybody.

Well, how about the small child? Well, we\'ve got a range of, like
Tylenol or acetaminophen has a range so you put it in the middle of the
range, you\'ve got almost 20 percent before you get out of the range
that the child has to be underweight. In addition, you\'re using length
which is ideal body weight. And real thin kids tend to have more water
relative to their size so you have a little bit of a buffer there.

So think about how far a child would have to fall off of the scale to
overdose with this. And they would be an outlier. That\'s not a normal
child. They\'ve got some kind of illness. They\'re 30 percent below
ideal weight. So outside of those children, you really could not
overdose anybody with this system.

This is, again, the idea \-- not a syringe to make it simpler but, you
know, this might work for acetaminophen and Motrin which are the same
dose per mLs. And so the child would be a yellow and you fill it up to
yellow and you pour it in a cup or you could pour it in a spoon. And
you\'ve given an accurate dose.

This, to me, I\'ve been talking about color-coded tools, like a
color-coded syringe. You could see a color-coded cup or measuring
device. But this is really the concept we\'re getting at. We\'re talking
about color-coded information. That mLs label that is on there is the
same mLs label that would be on a box of epinephrine for a code.

In other words, you get the color and you look in the color. And as an
international system, it could always be mLs. So you\'re in Belgium. And
you look at the box of medicine. And you look in the rainbow and your
kid is a yellow. And you look in the number and that\'s mLs. You do not
have to speak English to do that.

And if you\'re too poor to have a scale at home, you can always have a
paper wall chart.

And you can learn it in your own language. You could be Hmong and come
into America and they can explain to you that we use a color-coded
system here.

Or you people that may not be fluent in French, you could be in Belgium
or in France and your kid has a fever and you pick up a bottle of
medicine. And you look in your child\'s color and that has the dose in
mLs.

If it were tablets, it could have the number of tablets just as easily.

But it is an international way of giving information. And here\'s a cup.
And that\'s the four mL line. So a person that does not speak English
could walk up to a wall chart, look in the color, see the number,
recognize the number on whatever cup was in it and give the dose.

Is this too easy? Is this too unimportant? You know people don\'t feel
like treating fevers is all that important. And doctors know that it
doesn\'t matter. And we know that the public panics over it. But at the
very least, there\'s probably 10 percent of emergency department visit
occur strictly because the fever is not adequately treated.

It certainly would be cost-effective, it would pay for itself. How much
anxiety to those poor people that do think it matters when the kid has
104 fever? How about if they\'re Spanish? And in the middle of the
night, they\'re struggling with a fever. Why not give them a way to do
it?

This is just \-- you all know this probably \-- published studies. They
never give it right. When I talk in front of ER audiences, I always ask
them if they have ever had two or three kids in a row with the right
dose of Tylenol because you can almost write it up. Somehow the public
never seems to get the dose right.

And so these are just a summary here of some of the studies that have
been done. They all show less than 50 percent adequate treatment of
fevers with acetaminophen.

Evidence-based, Duke actually did three studies on this. The first two
were not published because they did not have historical details. In one
of the studies, 20 percent of the people did not speak English. They
found the same thing.

This is the one that was published in the [Archives of
Pediatrics]{.underline}. And it showed that, again, the very poor
performance by the public of dosing over-the-counter medications and
there was very close to 100 percent correct dosing in this particular
formula.

The conclusion of the authors, \"This study suggests a marked
improvement in the caregiver\'s ability to correctly determine and
measure an over-the-counter medication for their child using a
color-coded method compared with conventional methods.\"

There was an editorial review of this and this is a copy of that. And
the conclusion there speaks for itself. \"Using a simple color-coded
syringe with instructions for measuring acetaminophen doses makes it
less likely for parents to underdose and overdose their child with the
medicine.\"

Again, the implications of this are broad. We\'re talking about Tylenol.
But you\'re actually talking about any kind of an over-the-counter
medication. You\'re talking about every language that it could be done.
You\'re talking about color coding so that the public knows their
child\'s color. It\'s easier to remember. It\'s easier to track even if
it\'s a weight color.

You\'re talking about building on prevention systems where a child has a
color for Tylenol or Motrin and then is in the hospital and a drug comes
from the pharmacy, a chemotherapeutic agent that\'s potentially toxic.
It has the color of that kid on the drug. The child says, \"Whoa, I\'m
not a blue. I\'m a red.\" The parent who doesn\'t speak English.

The ability to tie this into infusion devices, defibrillators,
equipment, anything that has sizing associated with it.

You know why does it make sense to color code children because they
change. And they change \-- if you\'re an ER doc like me, if you\'re a
first responder taking a kid out of a swimming pool, if you\'re an ICU
nurse who is struggling with how to mix up an infusion, or you are a
parent who doesn\'t speak English in the middle night, and they\'re
color coded because they come in different colors. And color is truly a
universal language.

Thank you.

DR. SELIGMAN: Thank you very much. Panelists, do you have some
questions?

CDR. HOLQUIST: This concept is pretty intriguing to me. I guess I have
some questions with its use in OTC products where \-- maybe I\'m just
understanding the concept correctly.

Each one of these products that will be coming from the manufacturer,
whether \-- like with the case of Tylenol, it comes in a concentrated
formulation and it comes in the regular elixir. So each one of those
products would have their own color for that particular product?

DR. BROSELOW: No, no. That is a rainbow. That\'s a colored rainbow you
saw up there. It has all colors. And the rainbow is a way of giving
information. And it is concentration-specific.

In other words, the mLs in that rainbow are fixed to the drug that it is
in. In other words, the way you recognize concentration is at the level
where you apply that to the container. So by definition, the mLs are the
color.

CDR. HOLQUIST: So this would take the whole undertaking of kind of
making every manufacturer label their product exactly the same way?
Because some label with cc\'s, some label with mLs. And there\'s even
confusion among, you know, what that means versus \--

DR. BROSELOW: Well, any time there is confusion, then there is a
possibility \--

CDR. HOLQUIST: Right.

DR. BROSELOW: \-- of a standard system to reduce that, you know. So we
would hope that people going \-- and, of course, to go to a more
standard system would help with that.

I would like to say, you know, as a doctor, when I got into medicine \--
are you parents \-- a lot of you parents \-- didn\'t you always wonder
why \-- how come ten pounds isn\'t always a teaspoon? Right? How come?

Well, I was very naive. I started learning about some of this other
stuff. I thought well, you know why not. Because if you made the
so-and-so more concentrated, it wouldn\'t taste as good, you know? And
I\'ve got my whole company set up to do this. And I\'m not going to
change my concentration.

I think Tony Temple years ago wanted to have a standardization whereby
the dose was similar. And the problem was all the drug companies would
have to reformulate. I mean it\'s a ridiculous idea.

But the color takes care of that. You don\'t reformulate anything. From
the point of view of the person using it, it\'s always a blue dose, see?
We put the color on the bottle. We do with paper what you would have to
do by redoing your whole manufacturing process. We save you money. We
allow you to communicate.

We don\'t have your drug representatives going into \-- with a wonderful
new drug that\'s wonderful and spending a half an hour trying to figure
out how to get the doc to use it because doc is older like me and he can
only remember the doses he already knows.

So you give him pinwheels. And you give him this which all makes sense
when you get one or two or three or five. But when you have 10 or 20 or
30, it stops making sense.

So from the pharmaceutical industry point of view, having a standard way
to communicate \-- it doesn\'t have to be the only way. There can be
other ways. We\'re not trying to give anything less than you already
have. This is an additional system. But you can buy into it whenever you
come in and say this is the drug, the dose. And by the way, it\'s
standard color coding. The dose is standardized.

DR. SELIGMAN: So at present in emergency rooms, are these user applied?
In other words, in the emergency rooms, do they have to organize
themselves along this line if they use the tape? I saw drawers in a
crash cart that looked like they were corresponding to those colors as
well.

DR. BROSELOW: Right.

DR. SELIGMAN: And again, they emergency room would have to organize
itself in a way that puts the right endotracheal tubes and all the
various devices as well as drugs in the appropriate bins, is that right?

DR. BROSELOW: Right. They don\'t have to. But that\'s been what has
happened. Because, you know, we started out with the community
hospitals, which do not have a lot of resources. And for them it was a
no-brainer. You know they\'re not a children\'s hospital but it makes it
easier for them.

The thing about a system is not just that things fit. It\'s that
they\'re there. I found one of the biggest problems was that you had
four No. 2 tubes and one No. 7, and no No. 6. So our system makes you go
through everything. That\'s the advantage of a system. It makes you
think of every little portal and to try to fill that portal.

So yes, the tape is used probably in 80 to 90 percent of at least the
community hospitals in America. And it is used some abroad. The
equipment storage system, I mean when I went to Duke years ago, they
just took the tape and put color bins. I just saw an article in
Australia where they just took bins and put it in. But a lot of them use
that at least to store equipment.

DR. SELIGMAN: Given its claimed widespread use, has there been an
expression of interest on the behalf of device manufacturers for
labeling their products in a way that would correspond to the color
schema that you have?

DR. BROSELOW: Yes, GE actually \-- you know a number of years ago, there
was an issue. I don\'t know if you followed it about radiation,
excessive radiation in children.

DR. SELIGMAN: Yes.

DR. BROSELOW: That they were setting their CT scanners for adults. Why?
Because you never want to miss anything, you know, so you turn it up.
And there was an epidemiological study that there could be as many as
10,000 cases of cancer when those children grew up.

So the people at Duke got interested in working with GE to make settings
for children and also using our color code to make it easier. What they
found was one \-- and so they used the color code and they found two
things in their study. One is it was more accurate. I don\'t know why.
You\'d think they\'d be able to make a chart but for some reason it was.
But two was like there were 17 techs and like 16 of them preferred color
coding.

So what does that mean? It means you can do it. In other words, if it is
easy to do, people do it. And so we want to make it easy for people to
make this step.

So as the result of that, GE actually licensed the color code. And now
all their new CT scanners have the software in it that if the child
comes in with an armband or sticker and they want to use the color, they
can set it.

Jerome Medical makes cervical devices. And they color code those because
they have Miami J as their collars but they have sizing.

So our hope is we\'re looking at how it could work with infusion devices
and different kinds of manufacturers we\'ve talked to.

Had an FDA presentation with Meridian with the idea of color coding the
autoinjectors for children because they have a size problem. One of the
ironic things is the bigger autoinjector is for the smaller kids. So
they want to have a simple way of recognizing size.

We met with a manufacturer of bone marrow needles who is talking about
color coding that.

So we\'re just getting started with that. But our hope is that we would
set a platform. And once the platform were in place, other people could
tie into it and simplify things.

DR. SELIGMAN: Yes, Wiley?

DR. CHAMBERS: Do you envision this color wheel for to be on the box of a
medication? On the label of the bottle? As a pull-out? Where did you \--

DR. BROSELOW: This is information. In other words, we want to show that
you can use color to get information. As far as the exact tool that
people would use, I would say that we would need to communicate with the
people and what the issues are. Whether sizing is in issue in general, I
don\'t know the answer.

DR. CHAMBERS: Right. But you\'ve obviously thought about this for a
while. Where do you think it is most useful? To be on the carton?

DR. BROSELOW: On an over-the-counter medicine, I would like to see a
little universal label, mLs label, on any bottle that can be given to
children. That\'s what I would like to see.

DR. CHAMBERS: On the bottle? Or on the carton? Or both?

DR. BROSELOW: I would actually see it right on the bottle.

DR. CHAMBERS: Okay.

DR. BROSELOW: Because you take it out of the carton and so that\'s where
I would like to see it. I mean I would see the little rainbow there. I
would like to think of a little symbol that showed frequency. Because if
we had some way of showing the frequency or the number of times a day to
give it plus the dose in mLs, that would be truly international.

And so I think \-- I\'ve given some thought to that but I don\'t have a
good solution for that.

DR. CHAMBERS: Having spent time trying to fit everything that is
required to be on the label of a bottle \--

DR. BROSELOW: Yes.

DR. CHAMBERS: \-- I\'m just trying to envision where there is extra room
to go and put something else. Or what you can take off if you put this
on instead.

DR. BROSELOW: You\'d have to ask them what we\'d take off. But, yes, I
don\'t know the answer to that. And you\'d like it to be big. You\'d
like it to be so older people can read it. You know one of the things we
looked, as an error prevention system, was the size of decimal points.
And all those issues.

And I\'d like it to be so that somebody can wake up in the middle of the
night and look at a label and see a number and know the dose. So it
would be nice if there was room to make it larger. It certainly could be
in a little thing that came out that was a pediatric thing.

DR. SELIGMAN: How accepting has the sort of organized pediatric
community been in terms of the American Academy of Pediatrics and others
in adopting such a system? Are pediatricians at the point now of calling
and telling parents at well-child visits or on other visits that you are
a yellow or a white or a green?

DR. BROSELOW: In some ways, this has been very difficult for us to
decide how to do. The standard system has been present for a number of
years.

My biggest criticism of color coding would be how about if I train all
my residents and it isn\'t there? How about if it isn\'t there three
years from now? How broad is this going to be?

So it was our feeling that we had to fully develop the system and know
how everything worked. And then come out with it at the same time so
people would see the inevitability of it.

So we have taken a long time. Now we\'re kind of coming out of the
closet so to speak on this and that we have a number of centers,
Christian in Delaware, NYU in New York, Mayo Clinic ER, and a number of
other hospitals that have looked at this.

I can tell you there is a very strong interest in error reduction. I can
tell you that there is a huge anxiety about children from the lay public
to adults.

So we think the timing is correct for this. In some ways, I didn\'t know
whether to go over the counter, you know I have an agenda. I want to get
this going. In some ways, you could go to over the counter like at
Tylenol and they could push this agenda almost on to physicians coming
out of over the counter.

My feelings were I\'d like it to come out of medicine. I don\'t want
something to be foist on doctors. So what we\'re doing is kind of \-- my
goal was to communicate it through the medical community as a paradigm
shift when people start going to color-coded tools.

But then this came up and I was quite concerned, especially about my
friends with ISMP about the negativity of colors, you know. And I very
much wanted to answer that we see our system as an error prevention
system more like the red light and the green light.

In other words, one of the most successful error reduction systems in
the world is color coded. So we don\'t want to throw it all away. But it
has to be pretty darn universal.

And the other thing is there cannot be two color-coded systems. By
definition, you would have none. So one of the reasons explaining to
everybody say if you go in on the same one, then we have something that
can travel. It can travel to other countries.

And, you know, we have other goals for this. I\'m rambling. But car
restraints is another area where there is a lot of awkwardness about
information.

I presented this to their group about using length and color for car
restraints because it doesn\'t \-- it\'s a single measurement. It\'s a
surrogate for size, for weight, and for length. And you don\'t have to
speak English.

So we\'re interested in tying it into lots of things. But I think the
timing is right now so we\'re trying to get interest in it really.
That\'s why I\'m here.

DR. SELIGMAN: Any questions? Comments from the audience?

(No response.)

DR. SELIGMAN: Well, thank you very much.

DR. BROSELOW: Thank you.

DR. SELIGMAN: We appreciate your traveling today. You gave an excellent
presentation.

And I want to thank you all for attending today\'s meeting. Appreciate
all the speakers and their input and all the comments they\'ve made as
well.

And again, we want to remind everyone that you do have the opportunity
to submit written comments to the docket to our Dockets Management
Administrator by April the 7th. And these will all be taken into
consideration as the FDA considers any future plans regarding the use of
color in both drugs as well as devices.

Thank you very much.

(Whereupon, the above-entitled hearing was concluded at 12:43 p.m.)