[Federal Register: February 26, 2004 (Volume 69, Number 38)]
[Rules and Regulations]
[Page 9119-9171]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26fe04-24]
[[Page 9119]]
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Part III
Department of Health and Human Services
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Food and Drug Administration
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21 CFR Parts 201, 606, et al.
Bar Code Label Requirements for Human Drug Products and Biological
Products; Final Rule
[[Page 9120]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 201, 606, and 610
[Docket No. 2002N-0204]
Bar Code Label Requirement for Human Drug Products and Biological
Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a new rule
to require certain human drug and biological product labels to have bar
codes. The bar code for human drug products and biological products
(other than blood, blood components, and devices regulated by the
Center for Biologics Evaluation and Research) must contain the National
Drug Code (NDC) number in a linear bar code. The rule will help reduce
the number of medication errors in hospitals and other health care
settings by allowing health care professionals to use bar code scanning
equipment to verify that the right drug (in the right dose and right
route of administration) is being given to the right patient at the
right time. The rule also requires the use of machine-readable
information on blood and blood component container labels to help
reduce medication errors.
DATES: Effective Date: This rule is effective on April 26, 2004.
Compliance Dates: Drug products that receive approval on or after
the rule's effective date must comply with the bar code requirement
within 60 days after the drug's approval date. Drug products that
received approval before the final rule's effective date must comply
with the bar code requirement within 2 years after the final rule's
effective date. Specific information on how the rule will be
implemented can be found in section II.I of this document.
FOR FURTHER INFORMATION CONTACT: Philip L. Chao, Office of Policy and
Planning (HF-23), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-0587.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Introduction
II. Comments on the Proposed Rule and FDA's Responses
A. Who Is Subject to the Bar Code Requirement? (Sec. 201.25(a))
B. What Products Must Have a Bar Code? (Sec. 201.25(b))
1. Should Prescription Drug Samples Be Excluded From the Rule?
2. Which OTC Drug Products Must Have a Bar Code?
3. Must Vaccines Have a Bar Code?
4. What Other Types of Drugs Should Be Subject to a Bar Code
Requirement?
5. Should Medical Devices Be Excluded From the Rule?
C. What Must the Bar Code Contain? (Sec. 201.25(c)(1))
1. Should We Require the Bar Code to Contain the NDC Number?
2. Should the Bar Code Contain Lot Number and Expiration Date
Information?
3. Can Information Be Omitted from the Label to Accommodate the Bar
Code?
D. Does the Rule Require a Specific Type of Bar Code? (Sec.
201.25(c)(1))
1. Should the Rule Require Linear Bar Codes?
2. Should the Rule Impose Any Conditions on the Bar Code?
E. Where Does the Bar Code Go? (Sec. 201.25(c)(2))
F. Must Blood and Blood Components Bear ``Machine-Readable''
Information? (Sec. 606.121(c)(13))
G. Must Biological Products Have a Bar Code? (Sec. 610.67)
H. What Other Comments Did We Receive?
1. Comments Seeking More Action by FDA
2. Comments Relating to Bar Code Problems or Quality
3. Comments Regarding FDA's Future Involvement with Bar Codes
4. Miscellaneous Comments
I. How Will We Implement the Rule?
III. Legal Authority
IV. Environmental Impact
V. Paperwork Reduction Act of 1995
A. What Is the Estimated Information Collection Burden?
B. What Comments Did We Receive on Our Estimates?
VI. Federalism
VII. Analysis of Impacts
A. Introduction
B. Objective of the Rule
C. Estimate of Preventable Adverse Drug Events and Acute Hemolytic
Transfusion Reactions
D. The Final Rule
E. Description of Affected Sectors
1. Current Machine-Readable Technologies
2. Manufacturers and Packagers of Affected Products
3. Retail Outlets
4. Hospitals
5. Nursing Homes and Long-Term Care Facilities
6. FDA Oversight and Responsibilities
F. Regulatory Costs of the Final Rule
1. Introduction
2. Costs to Manufacturers and Packagers of Affected Products
3. Costs to Retailers and Distributors
4. Costs to Hospitals
5. Costs to the Food and Drug Administration
6. Total Regulatory Costs
G. Other Anticipated Expenditures
H. Reduction in Preventable Adverse Drug Events and Preventable
Acute Hemolytic Transfusion Reactions
I. Value of Avoided ADEs and AHTRs
1. Value of Avoided ADEs
2. Value of Avoided AHTRs
J. Aggregate Benefit of Avoiding ADEs and AHTRs
K. Cost Effectiveness of Bar Coding
L. Other Benefits of Bar Code Technology
M. Distributional Effects of Bar Code Technology
N. Comparison of Costs, Expenditures, and Benefits
O. Uncertainty and Sensitivity
1. Voluntary Share of Labeling Costs
2. Packaging Decisions
3. Implementation Period
4. Value of Mortality Associated with ADEs
5. Value per QALY
6. Boundary Analysis
7. Hospital Response Rates
8. Hospital Intercept Rates with Machine-Readable Technology
9. Productivity Losses in Hospital Wards
10. Investments by Hospital Size
P. Small Business Analysis and Discussion of Alternatives
1. Affected Sectors and Nature of Impacts
2. Alternatives
3. Outreach
4. What Comments Did We Receive on Our Economic Analysis?
Q. Conclusion
R. References
I. Introduction
In the Federal Register of March 14, 2003 (68 FR 12500), FDA (we)
published a proposed rule that would require certain human drug and
biological product labels to have a linear bar code (the March 2003
proposal). The proposal would require the bar code to contain the
drug's NDC number. For blood and blood components, the proposal would
require the use of machine-readable information on the container label.
Our intent was to help reduce the number of medication errors in
hospitals and health care settings by allowing health care
professionals to use bar code scanning equipment to verify that the
right drug, in the right dose and right route of administration, is
being given to the right patient at the right
[[Page 9121]]
time. For blood and blood components, the machine-readable information
would perform a similar function and help prevent errors such as
transfusion errors.
The preamble to the March 2003 proposal described the events that
led us to issue the proposal (see 68 FR 12500 through 12503), and we
refer readers to that preamble if they wish to obtain details on the
events, recommendations, meetings, and literature that shaped the
proposed rule. In brief, medication errors are a serious public health
problem, and putting bar codes on drug products is expected to
significantly reduce medication errors. Medication errors can occur at
several points from the time the physician prescribes the drug to a
patient to the time when the patient receives the drug. For example,
the physician may write a prescription for the right drug, but in the
wrong dose. The pharmacist might misread the prescription and provide
the wrong drug, or read the prescription correctly and dispense the
wrong drug. The health care professional administering the drug might
give it to the wrong patient or give it to the right patient, but at
the wrong time or in the wrong dose. Although most medication errors do
not result in harm to patients, medication errors can result and have
resulted in serious injury or death. Medication errors also represent a
significant economic cost to the United States; one article published
in 2001 (Ref. 30) estimated the direct cost to be $177.4 billion, while
another (Ref. 31) estimated the cost of preventable adverse drug events
in hospitalized patients to be $5,857 for each adverse drug event, with
the estimated annual costs for preventable adverse drug events for a
700-bed hospital to be $2.8 million.
Bar codes can help reduce or detect potential medication errors by
enabling health care professionals to check whether they are giving the
right drug via the right dose and right route of administration to the
right patient at the right time. The bar codes would be part of a
system, along with bar code scanners and computerized databases, where:
[sbull] A patient would have his or her drug regimen information
entered into a computerized database.
[sbull] Each drug would have a bar code. The bar code would provide
unique, identifying information about the drug that is to be dispensed
to the patient.
[sbull] In hospitals, health care professionals, such as
pharmacists and nurses, would use bar code scanners (also called bar
code readers) to read the bar code on the drug before dispensing the
drug to the patient and to read a bar coded wristband on the patient
before giving the drug to the patient. In an outpatient setting, the
health care professional (such as a pharmacist) could scan the bar code
on the drug and compare the scanned information against the patient's
electronic prescription information before giving the drug to the
patient.
[sbull] The bar code scanner's information would go to the computer
where it would be compared against the patient's drug regimen
information to check whether the right patient is receiving the right
drug (including the right dose of that drug in the right route of
administration). The system could also be designed to check whether the
patient is receiving the drug at the right time.
[sbull] If the identity of the health care professional
administering the drug were desired, each health care professional
could also have a bar code. The health care professional would scan his
or her own bar code before giving the drug to the patient.
Bar codes can also complement other efforts to reduce medication
errors, such as computer physician order entry (CPOE) systems (where a
physician enters orders into a computer instead of writing them on
paper, and the order can be checked against the patient's records for
possible drug interactions, overdoses, and patient allergies) and
pharmacy-based computer systems that use a bar-coded NDC number to
verify that a consumer's prescription is being dispensed with the
correct drug.
We (FDA) held a public meeting on July 26, 2002, to discuss a
possible rule to require bar codes on human drug products, blood, and
blood components (see 67 FR 41360, June 18, 2002). Nearly 400
individuals attended that public meeting, and many submitted comments
to us. We then published the March 2003 proposal. The March 2003
proposal would create a new Sec. 201.25 (21 CFR 201.25) entitled ``Bar
Code Label Requirements.'' (For biological products other than blood
and blood components, the bar code requirement would exist through a
cross-reference at a new Sec. 610.67 (21 CFR 610.67.) The proposal
also would amend the preexisting, voluntary provision regarding
``machine-readable'' symbols on blood and blood component container
labels at Sec. 606.121(c)(13) (21 CFR 606.121(c)(13) to require the
use of machine-readable information.
We received approximately 190 comments on the proposal, and almost
all comments supported the rule in whole or in part. For example, one
comment said that ``FDA is to be highly commended for both the proposed
regulation and the process leading to it'' while another said that the
rule was an ``excellent step toward reducing medication errors.'' Other
comments reported favorably on their own experiences with bar codes on
drugs. One comment from a hospital said that the hospital had recently
begun bedside verification of medications, using bar codes, and that
the bar codes were a valuable tool for reducing medication errors. A
comment from a health professional noted that his health care system
used bar codes to dispense patient medications and those using robots
to dispense medications reduced the manual error dispensing rate by 50
percent.
A few comments, however, were skeptical about the value of bar
coding drugs. For example, one comment described problems associated
with installing new technology in old buildings. The comment also
feared that our rule would cause hospitals to lose their accreditation
if they did not adopt bar coding technology. Another comment expressed
concern about the impact on nurses' workloads. The comment said bar
codes on drugs could cause nurses to spend more time administering
medications because of scanning errors or problems with the bar code,
but concluded that ``the ultimate outcomes will be worth the investment
for the manufacturers, the providers, and ultimately the patients.''
After reviewing the comments, FDA made several changes to the rule.
The principal changes between the proposed and final rule are as
follows:
[[Page 9122]]
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Proposed Rule Final Rule
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Would apply to prescription drugs (except Applies to most prescription
for samples) and to over-the-counter drugs (except for samples,
drugs commonly used in hospitals and allergenic extracts,
dispensed pursuant to an order intrauterine contraceptive
devices that are regulated
as drugs, medical gases,
radiopharmaceuticals, low-
density polyethylene form
fill and seal containers,
and prescription drugs sold
directly to patients) and
to over-the-counter drugs
commonly used in hospitals
and dispensed under an
order. We explain the
reasons for exempting
certain prescription drugs
in section II.B.4 of this
document.
-------------------------------------------
Did not contain a general exemption Contains a limited, general
provision exemption provision. We
explain the reasons for
creating a general
exemption provision in
section II.B.4.c of this
document.
-------------------------------------------
Would require a linear bar code that meets Requires a linear bar code
Uniform Code Council standards that meets Uniform Code
Council standards or Health
Industry Business
Communications Council
standards. We explain the
reasons for this change at
section II.D.1 of this
document.
-------------------------------------------
Would create a 3-year implementation Establishes different
period compliance dates depending
on when a drug was
approved. In general, the
rule is effective 60 days
after date of publication
in the Federal Register. If
a drug receives approval on
or after the effective
date, it must comply with
the bar code requirement
within 60 days of the
drug's approval date. If
the drug received approval
before the rule's effective
date, it must comply with
the bar code requirement
within 2 years of the final
rule's effective date. For
blood and blood components,
a 2 year compliance date
exists. We explain the
implementation of this rule
at section II.I of this
document.
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We describe and respond to the comments in section II of this
document. To make it easier to identify comments and our responses, the
word ``Comment,'' in parentheses, will appear before the comment's
description, and the word ``Response,'' in parentheses, will appear
before our response. We have also numbered each comment to help
distinguish between different comments. The number assigned to each
comment is purely for organizational purposes and does not signify the
comment's value or importance or the order in which it was received.
II. Comments on the Proposed Rule and FDA's Responses
A. Who Is Subject to the Bar Code Requirement? (Sec. 201.25(a))
Under proposed Sec. 201.25(a), manufacturers, repackers,
relabelers, and private label distributors of human prescription drug
products and over-the-counter (OTC) drug products regulated under the
Federal Food, Drug, and Cosmetic Act (the act) or the Public Health
Service Act (PHS Act) would be subject to the bar code requirement
unless they are exempt from the establishment registration and drug
listing requirements in section 510 of the act (21 U.S.C. 360).
In the preamble to the proposed rule (68 FR 12500 at 12503), we
acknowledged that some hospitals place bar codes on drugs themselves
and have reduced their medication error rates significantly, but we
stated that requiring manufacturers, repackers, relabelers, and private
label distributors to bar code their own products should be more
efficient and result in better quality bar codes because manufacturers,
repackers, relabelers, and private label distributors generally have
sophisticated manufacturing processes, labeling machinery, and quality
control systems that hospitals cannot afford. We added that bar coding
by third parties (such as hospitals) could increase the possibility of
a label error through the attachment of the wrong bar code and could
lead to inconsistent bar code quality; in fact, one organization that
submitted a comment at our public meeting on July 26, 2002, estimated
the error rate in hospital labeling to be approximately 17 percent
nationwide.
We also stated that requiring manufacturers, repackers, relabelers,
and private label distributors to bar code their own products and to
use the same bar coding standard would result in a more uniform bar
coding system that could be used regardless of a patient's or
hospital's location in the United States, and that this uniformity
would also make it easier for health care professionals to train
themselves on bar coding procedures and technique and make it easier
and less expensive for hospitals to buy bar coding equipment.
(Comment 1) One comment stated that hospital pharmacies should be
subject to the bar code requirements. The comment explained that
hospitals frequently compound drugs for pediatric use and that omitting
such compounded drugs from the rule would leave ``infants and children
without the protections that bar codes are intended to provide.''
Another comment argued that we should exempt nuclear pharmacies
from the rule. The comment claimed that a bar code requirement would
subject hospital personnel and employees to additional radiation
(because they would have to scan the bar codes).
(Response) Section 510(g)(1) of the act states that pharmacies
which maintain establishments in conformance with any applicable
local laws regulating the practice of pharmacy and medicine and
which are regularly engaged in dispensing prescription drugs or
devices, upon prescriptions of practitioners licensed to administer
such drugs or devices to patients under the care of practitioners in
the course of their professional practice, and which do not
manufacture, prepare, propagate, compound, or process drugs or
devices for sale other than in the regular course of their business
of dispensing or selling drugs or devices at retail
do not have to register their establishments or list their products
with FDA. Thus, if a pharmacy is exempt, under section 510(g)(1) of the
act, from our establishment registration and drug listing requirements,
the pharmacy is not subject to the bar code requirements.
We also note that drugs compounded at pharmacies generally would
not have NDC numbers. NDC numbers are assigned to drugs that are listed
under section 510(j) of the act, but, as we
[[Page 9123]]
explained earlier, section 510(g)(1) of the act would exempt a pharmacy
from the registration and listing requirements. Consequently, a
compounded drug would not be listed, would not be assigned an NDC
number, and would therefore lack the information required to be in the
bar code.
Regarding the comment claiming that a bar code requirement would
lead to greater radiation exposure for nuclear pharmacy employees, the
comment did not provide any evidence or data to show that using a bar
code scanner would constitute a significant or even appreciable risk or
that bar code scanners would undermine or compromise any existing
measures taken to protect such employees from radiation exposure.
Nevertheless, as we explain in our response to comment 24 in section
II.B.4.b. of this document, we have decided to exempt
radiopharmaceuticals from the bar code requirement.
(Comment 2) One comment said we should exempt hospitals,
institutional providers, and large clinics from the rule. The comment
interpreted the rule's reference to repackers and relabelers as
covering hospitals and other providers and said that hospitals and
other providers would still have to repack and relabel drugs (such as
intravenous solutions and mixes). The comment declared it would be
``unrealistic'' to expect hospitals and other providers to obtain NDC
labeler codes and ``participate in the NDC system.''
In contrast, several comments said we should extend the rule to
hospitals or expressed disappointment that the rule did not require
hospitals to use bar codes. For example, one comment said the Federal
Government should establish requirements so that hospitals would have
to adopt technologies to use the bar codes. Another comment said that
we should ``encourage,'' but not require, hospitals to use bar code
technology. The comment said that most hospitals would find it
difficult to adopt bar code technology due to the age of their
buildings and their construction.
Another comment asked us to clarify that relabeled, repackaged, or
privately labeled drugs must have their own NDC numbers. The comment
said that hospitals and pharmacies must not use the same NDC number
that the drug's manufacturer used.
(Response) Some comments appear to have misinterpreted the rule.
Repackers, relabelers, and private label distributors that are exempt
from the establishment registration and drug listing requirements in
section 510 of the act (see 68 FR 12500 at 12503; see also proposed
Sec. 201.25(a)) are not subject to the bar code requirements.
Hospitals, clinics, and public health agencies that ``maintain
establishments in conformance with any applicable local laws regulating
the practices of pharmacy or medicine and that regularly engage in
dispensing prescription drugs * * * upon prescription of practitioners
licensed by law to administer these drugs to patients under their
professional care'' are exempt from the establishment registration
requirements (see Sec. 207.10(b) (21 CFR 207.10(b)); as a result, such
hospitals, clinics, and public health agencies are also exempt from the
bar code requirements.
The rule also does not require hospitals to use or adopt bar code
technology. Hospitals are free to decide whether to take advantage of
the bar codes on human drug and biological products. Our legal
authority, in this case, extends to the products and not to hospitals.
Nevertheless, we advise hospitals and other potential bar code users
that we are aware of electromagnetic interference (EMI) problems
associated with the use of wireless technology products, such as cell
phones, local area networks (LANs), and personal digital assistants
(PDAs), in the vicinity of electrically-powered medical devices. EMI
problems are a particular concern in health care facilities as well as
home care settings. We caution that wireless bar code scanning
technologies may present similar concerns about their electromagnetic
compatibility (EMC) with other hospital equipment. We encourage
hospitals and other potential bar code users to consider EMC with
medical devices when developing their policies and implementing a bar
code scanning system. Additional information about EMC with medical
devices is available at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh/emc.
We recommend that interested parties gather information and conduct
research about wireless bar code scanners (or other scanning or reading
equipment) and their EMI potential on other medical devices. We also
encourage voluntary standards development organizations, such as the
Association for the Advancement of Medical Instrumentation, the Joint
Commission on Accreditation of Healthcare Organizations (JCAHO), the
American National Standards Institute (ANSI), and the International
Electrotechnical Commission (IEC) to work with us toward the goal of
coordinated policies, research, and standards development to ensure a
base level of EMC in all health care facilities. This would include
recommendations for safely deploying wireless technology in hospitals
and health care facilities.
As for entities that repack or relabel drugs, if a repacker,
relabeler, or private label distributor is subject to the establishment
registration requirement at section 510 of the act, then that person
would also be subject to the bar code requirements. We would expect
that repacker, relabeler, or private label distributor to use its own
NDC numbers on its products. In other words, a manufacturer, repacker,
relabeler, or private label distributor must not use an NDC number that
is not assigned to it. Use of another establishment's NDC number in the
bar code would cause the product to be misbranded under section 502(a)
of the act (21 U.S.C. 352(a)) because the drug's label would be
misleading.
B. What Products Must Have a Bar Code? (Sec. 201.25(b))
Proposed Sec. 201.25(b) would require bar codes on the labels of:
[sbull] All human prescription drug products, excluding samples;
[sbull] Biological products; and
[sbull] OTC drug products that are commonly used in hospitals and
dispensed pursuant to an order.
We proposed to exclude prescription drug samples because most
samples are given to patients at physicians' offices, and we did not
believe that physicians or patients would have or be inclined to buy
bar code scanners for their own use in the immediate future. We invited
comment as to whether we should require bar codes on prescription drug
samples and sought cost and benefit data associated with placing bar
codes on such samples (see 68 FR 12500 at 12505 and 12529).
As for OTC drug products, the phrase ``commonly used in hospitals''
reflected our primary focus of helping to reduce the number of
medication errors occurring in hospitals. We added the phrase,
``dispensed pursuant to an order,'' because we knew that some products
that are regulated as OTC drug products, such as mouth rinses and
toothpastes, are not likely to contribute to medication errors, and are
not dispensed in hospitals pursuant to a physician's or health care
professional's order. Thus, the phrase, ``dispensed pursuant to an
order,'' was designed to capture those OTC drug products that are
likely to contribute to medication errors. The preamble to the proposed
rule invited comment as to whether there was a better way to describe
the types of OTC drug products that should have a bar code (see 68 FR
12500 at 12506 and 12529).
[[Page 9124]]
The preamble to the March 2003 proposal also invited comment on
whether any specific product or class of products should be exempt from
the rule and the reasons for an exemption (see 68 FR 12500 at 12511
through 12512 and 12529).
1. Should Prescription Drug Samples Be Excluded From the Rule?
(Comment 3) Several comments said we should require bar codes on
prescription drug samples. One comment stated that bar codes on samples
would make it easier to monitor inventory or distribution to patients.
Another comment said that prescription drug samples are ``commonly
dispensed in numerous hospital settings,'' such as emergency
departments, and that ``the very nature of treatment and medication
administration (in an emergency department) presents unique challenges
for which bar coding would prove instrumental.'' The comment also
stated that JCAHO requires institutions to have policies and procedures
in place to control drug samples and requires quick retrieval of
recalled drugs, so hospitals must keep detailed records, ``often
including lot and expiration date, of drug samples dispensed to
patients.'' Another comment suggested that, rather than require bar
codes on all prescription drug sample labels, we could simply require
bar codes on the outer package because patients receive the entire
package rather than a portion of a drug sample.
Other comments also wanted bar codes on prescription drug samples
for reasons unrelated to medication errors. For example, one comment
said that bar codes on prescription drug samples would reduce the
amount of time spent tracking samples. Another comment said that bar
codes could help pharmacists identify samples that patients present to
them; the comment said that patients sometimes bring prescription drug
samples to pharmacists because they wish to continue receiving the same
drug. A third comment said clinicians might be confused if they had to
follow one procedure for bar coded prescription drugs and a different
procedure for nonbar coded prescription drug samples.
Conversely, several comments agreed with our decision to exclude
prescription drug samples from the bar code requirement. The comments
said there would be no benefit to bar coding such products, although
one comment suggested that we conduct a study to see how prescription
drug samples are used in institutional settings and to determine
whether they should be the subject of a future rulemaking. Another
comment agreed that bar coding prescription drug samples would not
enhance patient safety, but said that one possible benefit would be
that manufacturers could monitor disbursement of prescription drug
samples.
Other comments suggested that bar codes on samples could be
voluntary or noted that bar codes can fit easily on prescription drug
samples because their packaging is often larger than unit-dose
packaging (so that it is technologically feasible to put bar codes on
prescription drug packaging) and that the Uniform Code Council (UCC)
system requires bar codes on promotional products such as samples.
(Response) We decline to require bar codes on prescription drug
samples. The comments did not offer any data to contradict our position
that most prescription drug samples are dispensed by physicians in
their offices and that physicians and patients will not be inclined to
buy or use bar code scanners. We realize that bar codes could help with
inventory control and help monitor distribution of samples, but those
objectives have no bearing on medication errors or drug safety and are
outside the scope of this rule.
Although one comment did claim that prescription drug samples are
commonly dispensed in hospitals, particularly in emergency departments,
we could not determine whether the comment meant to say that hospitals
administer samples to patients or whether they simply provide samples
to patients to take home. We also could not determine whether such
practices are common in hospitals, but note that, under section 503(d)
of the act (21 U.S.C. 353(d), hospitals may distribute prescription
drug samples at the direction of a practitioner who is licensed to
prescribe such drugs and who received such samples. (However, sections
301(t) (21 U.S.C. 331(t)) and 503(c) of the act prohibit the sale and
purchase of drug samples.) If we assume that the comment pertained to
distribution of samples in hospitals, then we reiterate that the
physicians directing the distribution of the samples and the patients
receiving such samples will not be inclined to buy or use bar code
scanners. Consequently, requiring bar codes on prescription drug
samples would have little benefit insofar as medication errors are
concerned.
As for the possible use of bar codes in helping pharmacists
identify drugs presented by patients, we note that part 206 (21 CFR
part 206) requires imprinting on solid oral dosage forms. The code
imprint was designed to help identify solid oral dosage forms,
particularly in emergency situations, and to help consumers and health
care professionals identify drugs (see 58 FR 47958, September 13, 1993;
part 206). Thus, drug imprinting already exists to help emergency
departments, and pharmacists can also use the imprint codes to help
identify samples presented to them by patients.
As for the voluntary use of bar codes on prescription drug samples,
we do not object to such use.
2. Which OTC Drug Products Must Have a Bar Code?
(Comment 4) Several comments focused on OTC drug products. One
comment agreed that only OTC drug products commonly used in hospitals
and dispensed pursuant to an order should be required to have bar
codes. In contrast, an OTC drug firm stated that the rule's description
of OTC drug products might be clear to hospitals, but was unclear to
OTC drug manufacturers. The comment said that, instead of describing
the OTC drug products that must have a bar code, we should list OTC
drug products, categories of OTC drug products, and/or ingredients that
do not require bar codes. The comment said such a list would give
``clear direction'' as to those OTC drug products that are subject to a
bar code requirement.
Two other comments expressed similar views on listing OTC drugs.
One comment said we should list categories of OTC drug products that
would not have to have a bar code, whereas another comment said we
should list the types of OTC drugs that would or should be subject to a
bar code requirement.
(Response) We decline to revise the rule to describe the OTC drug
products that would be subject to Sec. Sec. 201.25 and 610.67 in terms
of specific drugs, categories, or ingredients. The comments' suggestion
that we list OTC drug products, categories, and/or ingredients would
effectively force us to engage in case-by-case analyses to decide
whether a particular OTC drug, category, and/or ingredient should or
should not have a bar code and force us to engage in repeated
rulemakings each time we wanted to modify the list. Additionally,
parties that objected to listing a particular OTC drug product or class
could attempt to challenge our decisions, creating an added burden on
our resources. The result would be a cumbersome, time-consuming,
resource-intensive, and inefficient administrative process that would
detract from, rather than contribute to, efforts to improve patient
safety. The original proposal's
[[Page 9125]]
formulation makes the distinction we are trying to draw and places the
burden on manufacturers, repackers, relabelers, and private label
distributors of OTC drug products to determine whether their products
are commonly used in hospitals and dispensed under an order.
We have, however, re-worded Sec. 201.25(a) to refer to ``over-the-
counter (OTC) drug products'' and to use the shorter term of ``OTC drug
products'' in the remainder of Sec. 201.25. This change corrects an
oversight in the proposed rule because it referred to ``OTC drug
products'' without explaining what ``OTC'' meant.
(Comment 5) Proposed Sec. 201.25(b) had explained that an OTC drug
is ``commonly used in hospitals'' if it is ``packaged for institutional
use, labeled for institutional use, or marketed, promoted, or sold to
hospitals.'' One comment stated that the rule's reference to OTC drug
products packaged and labeled for ``institutional'' use was confusing
because the rule also referred to ``hospitals.'' Thus, the comment said
we should clearly define the sites to which bar coded products must be
distributed and define ``hospital'' and ``institution.''
Two other comments suggested that we interpret ``commonly used in
hospitals'' as ``packaged for hospital use, labeled for hospital use,
or marketed, promoted, or sold to hospitals.'' Another comment said the
interpretation of the phrase, ``commonly used in hospitals,'' should
depend on a combination of two or more ``indicators,'' such as
``packaging designed for institutional use, package labeling for
institutional use, or marketing or promotion (including through sales
catalogues) to hospitals.'' The comment explained that our rule would
``inadvertently sweep a far larger range of OTC medicines into the
rule's coverage.'' It also asked us to clarify that an OTC drug
manufacturer would not be responsible for bar coding the drug if it was
``marketed, promoted, or sold to hospitals'' by someone else.
(Response) The proposed rule referred to ``institutional use''
because we knew that some OTC drug packages and labels state that the
drug is ``for institutional use'' or ``for institutional use only''
(see 68 FR 12500 at 12505). We did not intend to imply that the rule
would cover OTC drug products that were commonly used in
``institutions'' other than hospitals, and we have revised Sec.
201.25(b) to replace ``institutional use'' with ``hospital use.''
However, we also have added the parenthetical phrase, ``or uses similar
terms'' after ``labeled for hospital use'' to indicate that persons
subject to the rule should adopt a common sense interpretation of Sec.
201.25(b). For example, a manufacturer who labels an OTC drug ``for
institutional use only'' and sells that OTC drug to hospitals should
comply with the bar code requirement notwithstanding the fact that it
labeled the drug ``for institutional use only'' instead of ``for
hospital use only.'' In other words, we do not consider the OTC drug
label's use of the word ``institution'' or its avoidance of the word
``hospital'' as being the determining factor in whether an OTC drug
must comply with the bar code requirement.
As for defining what constitutes a ``hospital,'' the preamble to
the proposed rule interpreted the word ``hospital'' as ``a facility
that provides medical, diagnostic, and treatment services that include
physician, nursing, and other health services to inpatients and the
specialized accommodation services required by inpatients'' (see 68 FR
12500 at 12517, footnote 4 of table 2). We consider this interpretation
to be sufficient for the final rule, but decline to codify this
interpretation in the final rule. A codified interpretation of
``hospital'' would invite arguments as to whether a particular facility
purchasing OTC drug products was or was not a ``hospital,'' whether the
majority of purchasing institutions were or were not ``hospitals,''
and, as a result, would likely lead to further arguments about whether
a particular OTC drug product sold to such facilities was subject to
the bar code requirements. Engaging in such arguments would neither
enhance patient safety, nor would it be an efficient use of our
resources.
We also decline to interpret ``commonly used in hospitals'' as
requiring two or more ``indicators.'' If we were to make the change as
suggested by the comment, fewer OTC drug products would be subject to
the bar code rule despite their use in hospitals and despite their
potential for causing medication errors. For example, if we interpreted
the rule to apply only to those OTC drug manufacturers who directly
sold their products to hospitals, then an OTC drug manufacturer could
avoid the bar code requirement simply by selling the OTC drug products,
complete with labeling for ``hospital use,'' to wholesalers or
middlemen for resale to hospitals. Similarly, if we were to adopt the
comment's suggestion to change ``packaged for institutional use'' to
``packaging designed for institutional use,'' a firm could avoid the
bar code requirement by making no distinction between its packages for
retail sale and its packages for hospital use, because the package is
arguably not ``designed'' for institutional use.
(Comment 6) Two comments stated that the phrase, ``dispensed
pursuant to an order,'' is inappropriate because some institutions do
not have orders provided by physicians or because some institutions
allow nurses to request OTC drugs. Another comment suggested that we
refer to OTC drugs that are ``dispensed upon a prescription of a
practitioner licensed by law to administer a drug;'' the comment said
this language would be clearer and eliminate any confusion as to what
constitutes an ``order.''
Several comments suggested that we refer to ``non-prescription
drugs used therapeutically pursuant to a prescriber's order,'' although
one comment used the phrase ``pursuant to a rescuer's order.'' The
comments explained that the word ``therapeutically'' would exclude OTC
drugs such as toothpastes and mouth rinses. Another comment suggested
that the rule state that OTC drug products ``are excluded from the bar
coding requirements except for those OTC therapeutic drugs that are
packaged for institutional use or specifically marketed for use in an
institution for therapeutic purposes.''
(Response) The word ``order,'' in Sec. 201.25(b), is not confined
to any particular manner, document, or format for requesting a drug,
nor is it confined to any particular type of health care professional.
The phrase ``dispensed pursuant to an order'' should be interpreted as
applying to an OTC drug that is to be administered to a patient as
directed by a health care professional, regardless of whether he or she
is a physician, nurse, or other professional. Consequently, we decline
to revise the rule to refer to a ``prescription of a practitioner
licensed by law to administer a drug'' because those terms would be
more restrictive and would create more, rather than less, uncertainty
over the rule's applicability to OTC drug products. For example, the
word, ``prescription'' could be interpreted as requiring the
practitioner to write a prescription for the OTC drug product before it
could be administered to the patient. In contrast, an ``order'' could
be an instruction written on a patient's medical chart, and could even
be entered into the chart at the same time when the OTC drug is
administered. As another example, the phrase, ``practitioner licensed
by law to administer a drug'' could create uncertainty or disagreement
as to whether a person was a ``practitioner,'' whether he or she was
``licensed by
[[Page 9126]]
law,'' and whether that license included the ability to ``administer a
drug.''
Similarly, we decline to revise the rule to refer to ``non-
prescription drugs used therapeutically pursuant to a prescriber's
order.'' There is no apparent distinction between a ``non-prescription
drug'' and ``OTC drug product,'' and requiring such drugs to be used
``therapeutically'' could result in disagreements as to whether a
particular use was ``therapeutic.'' For example, a person might
interpret ``therapeutic'' as meaning that the OTC drug product must
have curative or healing properties and distinguish such drugs from
those whose purpose is prophylactic or intended to prevent disease.
Another person might distinguish between OTC drug products that provide
symptomatic relief and ``therapeutic'' OTC drug products by arguing
that providing symptomatic relief does not address the underlying cause
of a disease or condition and, therefore, is not ``therapeutic.'' We
can avoid such potential arguments by not referring to ``therapeutic''
use.
We did not understand the comment that referred to a ``rescuer's
order'' and did not believe the use of the word to be an appropriate
substitute for an ``order.''
(Comment 7) One comment suggested that the rule cover OTC drug
products that are intended to be dispensed intact and in the original
container as provided by the manufacturer, for use by inpatients. The
comment explained that this description would cover various OTC drug
products and also cover OTC drug products that are ``comfort
medications'' that nurses can request without a physician's order.
(Response) We decline to adopt the comment's suggestion. The
comment's suggested definition would encompass some OTC drug products,
such as mouth rinses and toothpastes, that are not likely to contribute
to medication errors but are nevertheless dispensed intact and in the
original container to inpatients.
(Comment 8) One comment asked us to exclude OTC drug samples from
the rule. The comment noted that we had excluded prescription drug
samples because prescription drug samples are usually dispensed in
physicians' offices and because we did not believe that physicians or
patients would be inclined to buy or use bar code scanners. The comment
claimed that the same rationale applied to OTC drug samples.
(Response) We decline to amend the rule as suggested by the comment
because an amendment is unnecessary. The rule requires bar codes only
for OTC drugs that are ``commonly used in hospitals'' and ``dispensed
pursuant to an order.'' OTC drug samples would fall outside this bar
code requirement because OTC drug samples are not ``commonly used in
hospitals'' and are not ``dispensed pursuant to an order.''
(Comment 9) One comment from an OTC drug manufacturer asked if the
rule applied to all packages of a specific OTC drug. The comment
explained that the firm uses a ``modified open stock catalogue'' that
includes all retail and some hospital-specific OTC drug products and
that hospitals can buy products from the catalogue. The comment asked
if the rule would require the firm to put bar codes on all OTC drug
products in the catalogue or whether the firm could put a bar code on
one or more OTC drug products and still offer OTC drug products without
bar codes in the same catalogue. The comment appeared to suggest that
hospitals could then decide which version (i.e., bar coded vs. nonbar
coded) to buy, and the OTC drug manufacturer would still be in
compliance with the rule.
(Response) We interpret the comment as meaning that an OTC drug
manufacturer may make two versions of the same OTC drug product. Both
versions would use the same drug (in the same dosage form and
strength); they would differ only with respect to the presence of a bar
code on the product labels. Under such a scenario, we agree that the
OTC drug manufacturer could, indeed, offer both the bar coded and
nonbar coded versions of the OTC drug product in the same catalogue for
hospital and retail sales, and we would consider the firm to be in
compliance with the rule.
However, if the OTC drug manufacturer had several different
versions of an OTC drug product that is commonly used in hospitals and
dispensed under an order, and the OTC drug manufacturer decided to put
the bar code only on one product, we might consider the OTC drug
manufacturer to be in violation of the rule. To illustrate, assume that
the OTC drug manufacturer makes three different dosages of a drug: A 50
milligram (mg) tablet, a 100 mg tablet, and a 200 mg tablet, and it
sells all three products to hospitals. If the OTC drug manufacturer
placed the bar code on the 50 mg tablet labels, but not on the 100 mg
and 200 mg tablet labels, we would not consider the OTC drug
manufacturer to be in compliance with the rule. In this scenario, we
would expect the OTC drug manufacturer to put bar codes on the 100 mg
and 200 mg versions of its product as well.
(Comment 10) One comment asked us to clarify that the phrases
relating to hospital use and to institutional use pertained only to OTC
drug products.
(Response) The comment understands the rule correctly. The rule
applies to all prescription drug products (except for prescription drug
samples, allergenic extracts, intrauterine contraceptive devices
regulated as drugs, medical gases, radiopharmaceuticals, low-density
polyethylene form fill and seal containers, drug products shipped by
manufacturers, repackers, relabelers, and private label distributors
directly to patients, and blood and blood components). We explain the
reasons for excluding these drugs later in this section.
Insofar as OTC drug products are concerned, the rule applies to
those OTC drugs that are commonly used in hospitals and dispensed under
an order.
(Comment 11) One comment stated that we should require bar codes on
Betadine. The comment did not explain why it singled out this
particular OTC drug, but stated that including drugs such as Betadine
would allow computerized databases to check for potential allergic
reactions.
(Response) Betadine is an iodine solution and an OTC drug product
that is commonly used in hospitals, but only some versions are
dispensed under an order. Thus, under the final rule, only those
versions that are both commonly used in hospitals and dispensed under
an order would be subject to the bar code requirement.
While Betadine has the potential to cause allergic reactions, it
would be impractical to revise this rule to impose a bar code
requirement based on a drug's potential for allergic reactions. For
example, an individual might be allergic to a color additive used in a
drug; another individual might be allergic to a different drug
component. Accounting for all potential allergens would require
additional data to be encoded, and it may be difficult to accommodate
more data on product labels.
3. Must Vaccines Have a Bar Code?
In the preamble to the March 2003 proposal, we invited comment on
the risks and benefits of including vaccines in the rule (see 68 FR
12500 at 12505 and 12529). We explained that we were sensitive to
possible adverse impacts on vaccine production and availability.
(Comment 12) Most comments, including comments submitted by
individual vaccine manufacturers and a pharmaceutical industry trade
association, said vaccines should be subject to a bar code requirement.
Some
[[Page 9127]]
comments also stated that we should require lot number and expiration
date information to be encoded for vaccines, too, because such
information is needed for accurate medical records.
In contrast, several comments suggested that we consider carefully
the impact of bar coding on vaccines. Although these comments did not
recommend exempting vaccines from the rule, neither did they appear to
fully support bar codes on vaccines. For example, one comment said that
bar codes on vaccines will have minimal impact because most vaccines
are administered in physicians' offices, and bar code scanners will not
be readily available at those offices. Several comments, submitted by
health professional societies or organizations, urged ``caution,''
stating that a bar code requirement could disrupt vaccine supplies and
create a burden that exceeded the benefits of bar-coded vaccines.
Another comment suggested that we create a separate regulatory process
for vaccines and that we ``engage'' the vaccine industry to address
data encoding issues.
(Response) Vaccines are subject to the final rule's bar code
requirements by virtue of being prescription drugs. The comments did
not show that the costs of bar coding vaccines exceeded the benefits,
and we note that vaccine manufacturers themselves did not indicate that
a bar code requirement would adversely affect vaccine production or
supplies.
We decline, however, to require inclusion of lot number and
expiration date information in a vaccine's bar code. As we stated in
the preamble to the March 2003 proposal, the costs associated with
encoding lot number and expiration date information appear to exceed
the benefits (see 68 FR 12500 at 12507-12508). The comments did not
provide evidence that would alter the cost-benefit analysis regarding
lot number and expiration date information, so the final rule does not
require such information in the bar code. Nevertheless, as we stated in
the preamble to the March 2003 proposal, we will not object if firms
voluntarily encode lot number and expiration date information (see 68
FR 12500 at 12508).
We also decline to establish a separate regulatory process for
vaccines. We presented our concerns regarding bar codes and vaccines in
a notice of a public meeting (see 67 FR 41360, June 18, 2002) and in
the preamble to the March 2003 proposal (see 68 FR 12500 at 12504 and
12505). This rulemaking process, therefore, has given vaccine
manufacturers and other interested parties ample notice and opportunity
to participate on bar coding matters, so there is no public health need
to create a separate regulatory process for vaccine bar codes.
4. What Other Types of Drugs Should Be Subject to a Bar Code
Requirement?
a. Comments seeking to cover more drug products. (Comment 13) Many
comments stated that we should require bar codes on all human drugs.
Health care professionals and hospitals submitted most of these
comments, but the comments frequently gave no rationale for covering
all human drugs or argued that failure to require bar codes on all
human drugs would force hospitals to repack drugs and apply bar codes
themselves, thereby increasing the risk that hospitals might apply the
wrong bar code.
(Response) We decline to require bar codes on all human drugs. By
focusing on prescription drugs and certain OTC drug products, the rule
covers those drugs that are most likely to be involved in medication
errors. We also note that the rule should reduce the need for hospitals
to put bar codes on drugs.
If we required bar codes on all human drugs, then some drugs (such
as samples) would have bar codes even though they are used outside the
hospital setting and in situations where the patient is unlikely to
have access to, or be willing to buy, scanning or reading equipment to
read the bar code. Other drugs, such as certain toothpastes, mouth
rinses, and even homeopathic drugs (which are ``drugs'' under section
201(g) of the act (21 U.S.C. 321(g)) would also have to have bar codes
even though they are not associated with medication errors. Thus, bar
coding all human drugs is unnecessary and would not contribute
significantly to an overall improvement in patient safety.
(Comment 14) Two comments asked us to require bar codes on
investigational new drugs or asked if investigational new drugs are
subject to the rule.
(Response) Investigational new drugs have not been assigned NDC
numbers because the number of investigational new drugs is constantly
changing, and that constant change would exhaust the number of
available NDC numbers quickly.
In addition, bar codes on investigational new drugs also could
result in misleading information or compromise the clinical study. For
example, if the clinical trial involved placebo controls, and the
placebo used the same bar code as the investigational new drug, the bar
code could mislead the computerized database into believing that the
patient received an active ingredient rather than a placebo. If the
placebo used a different bar code compared to the investigational new
drug, the different bar code would reveal the difference between the
placebo and the investigational new drug and introduce bias into the
clinical study. Consequently, we decline to require bar codes on
investigational new drugs.
b. Comments seeking to exclude specific drug products. Although
nearly all comments supported the rule, many comments sought to exempt
or exclude particular products or classes of products from a bar code
requirement or asked us to create a provision allowing case-by-case
exemptions. In contrast, many comments, submitted mostly by hospitals
and individuals, opposed any exemptions or opposed exemptions for
specific products.
(Comment 15) Several comments asked us to exclude allergenic
extracts from the rule. The comments argued that allergenic extracts
encompass hundreds of different antigens, are sold directly to
physicians, physician group practices, and clinics (or are not commonly
used in hospitals) where bar code scanning equipment would not be used
or where physicians and patients would have no incentive to buy bar
code scanners, and that allergenic extracts do not always have NDC
numbers. Another comment said that allergenic extracts are unique and
tailored to each patient, so a manufacturer that had to comply with the
bar code requirement would have to obtain NDC numbers for each extract,
and this process would increase the likelihood of labeling errors. The
comment also stated that a bar code requirement for allergenic extracts
would be ``unduly burdensome'' and expensive; the comment estimated the
cost of putting bar codes on allergenic extracts to be more than
$120,000 for one firm alone.
(Response) We agree that allergenic extracts are used primarily in
physicians' offices and that physicians and patients are not likely to
buy or use bar code scanners. Consequently, we have excluded allergenic
extracts from the final rule.
Because we have decided to exempt allergenic extracts, we do not
find it necessary to address the comments' claims regarding burdens and
costs.
(Comment 16) Some comments asked us to exempt products that are
packaged together (``copackaged products''). One comment gave examples
of products sold with titration packages or sold with different
strengths or types in a package or carton that are used together. The
comment explained that each
[[Page 9128]]
component could have its own NDC number, and asked what NDC number
would be used for the copackaged product.
(Response) Even if two products are packaged together, and each
product has its own NDC number, the copackaged product would have its
own distinct NDC number. Thus, in the comment's example, the NDC number
in the bar code would reflect the copackaged product and be distinct
from the NDC numbers for the individual products, and so there is no
reason to exclude copackaged products from the rule.
(Comment 17) Many comments asked us to exclude medical gases from
the rule. The comments explained that compressed and liquid medical
gases should be exempt from the rule because:
[sbull] Gas cylinders are located at a central supply point away
from patients (so bar codes cannot be scanned easily);
[sbull] There is no easy way to affix a bar code at the quick-
connect patient usage area that would discriminate between gas
manufacturers;
[sbull] It is not technologically or financially feasible to have
bar codes or to expect paramedics (who may be administering a medical
gas) to use scanners;
[sbull] Cylinders and/or connectors are specific for gases;
[sbull] Cylinders are color-coded to reduce the potential for
error;
[sbull] Gases, unlike other drugs, have dosages that vary per
patient; and
[sbull] There are no known adverse events linked to medical gases.
Other comments asked us to exempt oxygen and medical gases for home
use, stating that patients are unlikely to have bar code scanners in
their homes, or that, for oxygen, the comment knew of no adverse
reactions between oxygen and other drugs.
(Response) We agree that medical gases should be exempt from the
bar code requirement. We do not, however, agree with all of the
comments' arguments for exempting medical gases.
We are exempting medical gases from the bar code requirement
because we conclude that bar codes on medical gases are not the best
way to address medication errors associated with such drug products. We
agree that, because medical gas cylinders are most frequently located
at a central supply point away from patients, bar codes would not be
scanned easily or in sufficiently close proximity to patients.
We also agree that there is no easy way to affix a bar code at the
quick-connect patient usage area that would differentiate among gas
manufacturers, and that the majority of medical gas cylinders are not
patient-specific, but, rather, are used to administer medical gas to
multiple patients. Because of these factors, which are unique to the
administration of medical gases, we believe that bar codes are not the
best way to address medication errors associated with medical gases.
We disagree with the arguments regarding the number of medical gas
medication errors and the existence of adequate safeguards against such
errors. The comments state that there have been very few medical gas
medication errors. Low numbers of medication errors, alone, cannot
justify an exemption. For example, if the type of medication error is
serious (such as an error that results in death), then it would be
difficult to justify an exemption on the grounds that a ``low'' number
of deaths occur. Moreover, we have no basis to establish a threshold or
baseline number of medication errors that would determine whether a
particular drug had to comply with the bar code requirement. Even if we
could establish such a threshold or baseline figure, that figure would
be subject to challenge because health care professionals are not
required to submit adverse event reports to us; in other words, the
adverse event reporting system can signal the possible existence of a
problem, but it cannot reliably predict the frequency with which such
problems may occur.
We also disagree with the comments' claim that current provisions
for the color-coding of high-pressure cylinders sufficiently protect
against medication errors. At this time, color-coding of high-pressure
cylinders is an industry recommendation rather than a requirement, so
we cannot assume that all affected parties will choose to follow the
recommendation. Additionally, injuries and deaths have resulted from
administering medical gas from incorrectly colored high-pressure
cylinders.
We also disagree with the comments' claim that medical gas
containers have ``unique connectors and valves'' that decrease the
potential for medication errors. Like color-coding, the use of unique
connectors and valves is an industry recommendation and not a
requirement. Our experience indicates that these connectors and valves
can be and have been compromised such that incorrect gas has been
administered, resulting in deaths and injuries.
Although we do not believe that bar codes are the best way to
reduce medication errors in the administration of medical gases, we
recognize the need for preventing such errors and have issued guidance
on the matter, including a ``Draft Guidance on the Current Good
Manufacturing Practice for Medical Gases'' (68 FR 24005, May 6, 2003),
as well as a ``Compressed Medical Gases Guideline'' (February 1989). We
intend to continue to evaluate medication errors associated with
medical gases, and, as necessary, we may propose a regulation to reduce
or prevent those errors.
(Comment 18) Two comments focused on contraceptives. One comment
asked us to exempt oral contraceptives. The comment stated that it will
be difficult to put bar codes on oral contraceptives because the
tablets are contained in individual blister cells. The comment noted
that oral contraceptives also have information regarding drug regimen
compliance and placebos built into the package. The comment added that
oral contraceptives are used outside the hospital setting.
The other comment asked us to exclude the Copper T intrauterine
contraceptive and other intrauterine devices that are regulated as
drugs. The comment asserted that these products are inserted into
patients by physicians, are used outside hospital settings, and present
no potential dosage error or administration error.
(Response) We decline to exclude oral contraceptives from the rule.
Although oral contraceptives are contained in individual blister cells,
those cells are usually placed in a single package with a single label,
so the bar code would go on the label rather than on each individual
blister cell. As for their use, we agree that oral contraceptives are
used outside hospital settings, but do not believe that they are never
used in hospitals.
As for the Copper T intrauterine contraceptive and other
intrauterine products, we agree that such products, when used as
specified, do not present medication error risks in the same manner as
other prescription drug products, and we have excluded them from the
rule. (These intrauterine contraceptive products are devices, but are
regulated as drugs.) We also note that some hospitals may have
additional procedures, such as requiring informed consent, before these
intrauterine products are inserted, and those procedures may further
reduce the risk of error.
(Comment 19) One comment asked us to exclude cosmetic-drug products
which the comment characterized as not being subject to dosage
limitations, such as anti-dandruff shampoo, deodorants, skin
protectants, soaps, and sanitizers.
(Response) We decline to amend the rule as requested by the
comment. Most products described by the comment would be OTC drug
products and
[[Page 9129]]
probably would not be dispensed under an order. As a result, such
products would not be subject to the bar code requirements. (It is also
possible that some products, such as soaps, would be considered to be
cosmetics rather than OTC drug products and would also be outside this
rule.) We reiterate that only OTC drug products that are commonly used
in hospitals and dispensed under an order are subject to the bar code
requirements.
(Comment 20) Several comments sought an exemption for diluents. (A
diluent is an agent, usually a liquid, that dilutes a substance (a
drug, in this case) or makes it less potent or less irritating.) One
comment claimed that diluents are not drugs, but acknowledged that some
diluents do have NDC numbers. Another comment would not put bar codes
on diluents that are packaged with another drug product because, the
comment asserted, misidentification could occur after the diluent has
been reconstituted with the other drug product. Another comment
declared that bar codes on diluents should be voluntary and driven by
the market rather than by regulation. Several other comments mentioned
diluents or drug/diluent kits in a list of small products that, in the
comments' view, warranted a waiver from the bar code requirement.
(Response) We decline to exclude diluents from the rule. Diluents
are drugs under section 201(g)(1)(D) of the act if they are intended to
be components of a drug. We are aware of medication errors involving
diluents, so bar codes on diluents might help reduce or eliminate such
errors. For example, bar codes on diluents could help prevent the
following types of medication errors involving diluents:
[sbull] Use of the incorrect or improper diluent. Certain drug
products are compatible with specific diluents, so using the incorrect
diluent can compromise patient safety, especially if the incorrect
diluent causes a precipitate to form that is not recognized when the
drug is administered. Some precipitates are not recognizable by the
human eye. An incorrect diluent can also be a problem if the patient
has a particular medical condition (e.g., a diabetic patient receiving
a diluent consisting of dextrose in water rather than normal saline). A
bar code could alert a health care professional to the presence of an
incorrect or improper diluent.
[sbull] Use of the incorrect amount of diluent. This can cause an
incorrect final concentration of a drug, resulting in either an
overdose or underdose of the prescribed drug. A bar code could verify
that a diluent's amount was correct.
[sbull] Use of a diluent alone. We have reports where diluents were
administered without the active ingredient. This error appears more
likely to occur when the diluent and drug are removed from their
package. In one case where a patient was supposed to receive an
antibiotic oral suspension which was supplied as a lyophilized powder
in a small bottle and milky white diluent in a larger bottle, the
patient received the diluent only and not the antibiotic itself. A bar
code could alert a health care professional that he or she is
administering a diluent only.
[sbull] Incorrectly packaged or labeled diluents. There have been
cases where a package was supposed to contain a diluent and active drug
ingredient, but the product was incorrectly packaged so that it
contained two vials of diluent. A bar code could alert a health care
professional that the package contains only diluents.
If, as one comment indicated, a diluent does not have an NDC
number, an NDC number should be obtained for that product. If a diluent
is packaged with another drug, then, as we stated in our response to
comment 16 of this document, the diluent, the drug, and the copackaged
product would each have its own distinct bar code. Thus, if the diluent
were separated from the drug in a copackaged product, the diluent would
still have its own distinct bar code, and that bar code could be
scanned.
(Comment 21) One comment asked that we exclude drug products that
are shipped directly to patients. The comment gave an example of
peritoneal dialysis solutions and said that an exclusion would be
appropriate because patients would not be inclined to buy and use bar
code scanners within their homes. The comment also claimed that the
product it shipped is not typically used in hospitals.
(Response) We agree, in part, with the comment. If a prescription
drug product is shipped directly from a manufacturer, repacker,
relabeler, or private label distributor to a patient, then we will not
require that product to be bar coded. We agree that patients will not
have or be inclined to buy scanners for use within their homes.
However, similiar to our response to comment 9 in section II.B.2 of
this document, if the same prescription drug product is marketed to
hospitals, then we will expect that drug to have a bar code. In other
words, to use the comment's example of a peritoneal dialysis solution,
a manufacturer could produce two different versions of the same
product; the version sold directly to patients would not have to have a
bar code, but the version that is intended for sale to hospitals will
be subject to the bar code requirement. By requiring the latter version
to be bar coded, we will help prevent or reduce medication errors in
the hospital.
(Comment 22) Several comments asked us to exclude nebules from the
rule. (A nebule is a vial or container that holds a drug, usually in
liquid form, before the drug is administered or dispensed in a device
called a nebulizer.) The comments explained that we have been reluctant
to approve nebules with a label due to concerns that labeling
components could leach into the nebule and contaminate the drug. One
comment added that, even if we were to approve a label on a nebule, it
was unclear how a manufacturer could print the bar code.
Another comment asked whether the rule should apply to
pharmaceuticals packaged with low-density polyethylene (LDPE) form fill
and seal containers. The comment explained that placing a bar code on
such products would present a drug stability issue. The comment said
that if the rule applied to these products, then drug manufacturers
would need additional time to comply with the rule because they would
need to conduct stability tests.
(Response) The comments are correct that printing a bar code on
such products could introduce volatile impurities into the drug
(because the ink from the bar code could leach into the drug). We have
provided guidance on LDPE container closure systems in ``Guidance for
Industry on Inhalation Drug Products Packaged in Semipermeable
Container Closure Systems'' (July 2002).
However, we also know that some products may be packaged with a
foil overwrap. Consequently, we are granting a limited exemption. We
will not require a bar code on LDPE form fill and seal containers that
are not packaged with an overwrap, due to the potential leaching and
contamination problem. (We do not need to mention nebules in this
limited exemption because nebules are LDPE form fill and seal
containers.) If the product is packaged with an overwrap, then we will
expect the bar code to be displayed on the overwrap. A bar code on the
foil overwrap (the secondary protective packaging) for individual or
multiple LDPE units will not be in direct contact with the drug
product, and the foil overwrap will prevent the ink and other
impurities from contaminating the drug.
[[Page 9130]]
(Comment 23) One comment asked us to exclude prescription dental
drugs from the rule. The comment claimed that prescription dental drugs
are not used in hospitals and are applied by dentists in their offices
or prescribed for home use, so bar codes would not be helpful.
(Response) We decline to exclude prescription dental drugs from the
rule. We believe that prescription dental drugs are used in hospitals,
so bar codes on prescription dental drugs would help prevent medication
errors.
(Comment 24) One comment said we should exempt radionuclear drugs
from the rule. The comment explained that the outside containers of
radiopharmaceuticals are lead ``pigs'' that encase syringes and vials
and are used to ship radioactive materials. The lead pigs are recycled,
so any bar codes on the pigs would have to be removable. However, the
comment claimed, a removable bar code on the lead pigs would require
new labeling or shrink wrapping equipment, thus leading to a
significant financial burden on nuclear pharmacies. The comment added
that radiopharmaceuticals have a low ``misadministration'' rate of 30-
40 reportable ``events'' annually compared against more than 14 million
nuclear medicine procedures in 2002. The comment also claimed that a
bar code would require nuclear pharmacies to amend their Nuclear
Regulatory Commission (NRC) Agreement State licenses because the
licensing authority would have to approve all labeling changes.
(Response) We agree that radiopharmaceuticals prepared at nuclear
pharmacies should be exempt from the bar code requirement. The comment
correctly stated that radiopharmaceuticals have a low misadministration
rate. According to NRC data, the number of reportable medical
misadministrations of radiopharmaceuticals has been in the range of 32
to 42 out of more than 14 million administrations per year for the last
5 years. The highest number of reportable misadministrations occurred
in 1998, when there were 42 reportable events; this represented the
highest total since the NRC began collecting data under the Government
Performance and Results Act of 1992.
Low medication error rates are not, however, sufficient to warrant
an exemption from the bar code requirement. Instead, our principal
reason for exempting radiopharmaceuticals is that NRC regulations
pertaining to the medical use of radiation byproducts render bar codes
unnecessary for patient safety. For example, NRC regulations require,
in many cases, that radiopharmaceuticals be administered under a
written directive that ensures verification of a patient's identity
before each administration (see 10 CFR 35.40(a) through (b), and
35.41(a) through (b)). We believe that NRC regulations pertaining to
the use of radiation byproducts provide sufficient safeguards in
preventing medication errors involving radiopharmaceuticals, and,
because of this alternative regulatory program for these products, the
benefits associated with a bar code would not justify the costs.
Because we have decided to exempt radiopharmaceuticals from the bar
code requirement, we do not need to address the comment's other claims
regarding labeling, packaging, and financial burdens.
(Comment 25) One comment, submitted by an OTC drug manufacturer,
asked us to exempt its OTC drug products due to their ``distinctive
form'' and ``clear labeling.'' The comment said that medication errors
for its products (such as ready-to-use enemas, suppositories, and
medicated topical creams) are ``exceedingly rare.''
(Response) We decline to exclude OTC drug products that purport to
have a ``distinctive form'' and ``clear labeling.'' A product's
``distinctive form'' and labeling do not preclude the possibility of
drug interactions, wrong drug, wrong dose, wrong route of
administration, or other types of medication errors.
We also decline to exclude OTC drug products, or even prescription
drug products, from the rule even if their potential for medication
errors is ``exceedingly rare'' (as the comment claimed). We have no
basis to establish a threshold or baseline medication error rate that
would determine whether a product should have a bar code, and even a
``low'' medication error rate could result in death or harm to
patients. Furthermore, if we linked the bar code to a drug's medication
error rate, the result could be that a drug might be bar coded at one
time if its medication error rate exceeded the threshold, but not bar
coded once the medication error rate fell below that threshold, and
this could create confusion. For example, assume that the rule based
the bar code requirement on a medication error rate of 5 percent. If
Drug X had a medication error rate of 5.2 percent in Year A, it would
be bar coded. If Drug X had a medication error rate of 4.9 percent in
Year B, then it would not be bar coded. However, in all likelihood, in
Year B, both bar coded and nonbar coded versions of Drug X would exist
in the marketplace. If Drug X's medication error rate was 5.1 percent
in Year C, the drug would, again, be subject to the bar code
requirement. In such circumstances, the bar code would lose its value
and reliability, insofar as medication errors are concerned, because
hospitals would confront a constantly changing environment of drugs
that have or lack bar codes, and hospitals would either not rely on
such codes or lose confidence in the bar code system.
(Comment 26) One comment asked whether pharmacy-compounded
prescription drugs would be subject to the bar code requirement.
(Response) As we noted in the response to comment 1 of this
document, under section 510(g) of the act, pharmacies:
which maintain establishments in conformance with any applicable
local laws regulating the practice of pharmacy and medicine and
which are regularly engaged in dispensing prescription drugs or
devices, upon prescriptions of such practitioners licensed to
administer such drugs or devices to patients under the care of such
practitioners in the course of their professional practice, and
which do not manufacture, prepare, propagate, compound, or process
drugs or devices for sale other than in the regular course of their
business of dispensing or selling drugs or devices at retail
do not have to register their establishments or list their products
with FDA. Thus, a pharmacy that compounds drugs in accordance with this
provision would probably fall outside Sec. 201.25(a) and compounded
drugs made by that pharmacy would not have to bear a bar code.
We also note that pharmacy-compounded drugs do not have NDC
numbers.
(Comment 27) Several comments focused on drugs in small vials or
containers. Comments from several drug manufacturers and a trade
association suggested that we exempt small vials and/or small
containers from the rule, and several of these comments mentioned 5
milliliter (mL) vials, suppositories, small ophthalmic containers,
prefilled syringes, and blister packs as examples of products that need
an exemption. The comments stated that some vials or containers would
be too small for a bar code. One comment suggested exempting vaccine
unit-of-use containers if a manufacturer demonstrated an inability to
apply a bar code due to space limitations.
In contrast, several comments strongly opposed exemptions for small
vials and ampules. These comments explained that many of these products
are high-
[[Page 9131]]
risk medications or that most injectable products come in small vials
or ampules. Other comments said that liquid medications are more often
linked to medication errors than solid dosage forms, so creating an
exemption for vials and ampules would undermine the rule's
effectiveness. Other comments opposed exemptions for small vials
because the absence of a bar code would force hospitals to apply bar
codes to the products themselves, and this would create the potential
for labeling errors by the hospital.
One comment, submitted by the UCC, stated that, ``No [UCC]
pharmaceutical member has presented the UCC with a healthcare product
too small for a [Reduced Space Symbology] symbol.'' However, the UCC
could not preclude the possibility that some small product could not be
bar coded, although it did note that one firm had put bar codes on
vials as small as 1 mL. The UCC comment also contained attachments
describing how several pharmaceutical manufacturers (Abbott
Laboratories, Baxter Healthcare Corp., Pfizer, Inc., and Aventis
Behring) had decided to put bar codes on injectable pharmaceuticals,
intravenous solutions, and other drug products.
(Response) We decline to exempt small vials or containers
(including suppositories, prefilled syringes, and other small products
for which comments sought exemptions). We agree that the risk of
medication errors for these products cannot be ignored, and we also
find the UCC's comments persuasive. If several pharmaceutical companies
have already shown their ability to place a bar code on a 1 mL vial, we
cannot justify a blanket exemption for comparatively larger products,
such as 5 mL vials, and prefilled syringes.
Furthermore, we note that Sec. 201.25(c) requires the bar code to
appear on the drug's label. For some products described by the
comments, the drug's label appears on an overwrap or packaging.
Alternatively, it may be possible to modify the drug's immediate
container to accommodate a label bearing a bar code.
c. Comments seeking a general exemption provision. (Comment 28) In
the preamble to the March 2003 proposal, we explained our reasons for
not including a general exemption provision (see 68 FR 12500 at 12511
through 12512). We noted that industry-conducted pilot studies had
placed reduced space symbology (RSS) bar codes on small vials and that
those studies suggested that almost all products are capable of bearing
a bar code. We also pointed out practical problems with an exemption
provision, such as potential arguments as to whether it was
``feasible'' to affix a bar code and the resources that would be needed
to deal with exemption requests (id.). Nevertheless, the preamble to
the March 2003 proposal invited comment on whether we needed to create
a waiver provision and how we could create a provision that would
minimize the potential for misuse (see 68 FR 12500 at 12529 (question
8)).
Most comments opposed a general exemption or waiver provision. The
comments said we would find ourselves expending resources to deal with
exemption requests and that exemptions would cause more harm than good.
Some comments opposed creating an exemption mechanism because they
would prefer to have manufacturers repack their products or develop
packaging that would support a bar code. Other comments noted that, if
we exempt various products from the rule, hospitals will be forced to
bar code those products themselves, and this could result in labeling
errors and require hospitals to rely on two different data systems (one
for bar codes with NDC numbers and another for drugs that the hospital
has bar coded itself).
A few comments suggested that we create an exemption provision that
would consider requests on a case-by-case basis or would be
``limited.'' The comments did not suggest how we might prevent misuse
of an exemption provision. Another comment asked that we define an
exemption review process.
(Response) Given the number of comments we received requesting an
exemption for a specific product or class of products, the fact that
the final rule contains certain categorical exemptions requested by
some comments, and our inability to predict every future product or
class of products for which an exemption might be justified, we felt it
would be prudent to add a general exemption provision to the rule.
Consequently, we have added a new Sec. 201.25(d) which states that we
may, on our own initiative or in response to a written request from a
manufacturer, repacker, relabeler, or private label distributor, exempt
a drug from the bar code requirement. The exemption request, under
Sec. 201.25(d)(1)(i), must document why compliance with the bar code
requirement would adversely affect the drug's safety, effectiveness,
purity, or potency or not be technologically feasible. The request must
also explain why the problem cannot be reasonably remedied by measures
such as package redesign or use of overwraps. Alternatively, under
Sec. 201.25(d)(1)(ii), the request must document why an alternative
regulatory program or method of product use renders the bar code
unnecessary for patient safety. For example, as explained earlier in
our response to comment 24 of this document, we exempted
radiopharmaceuticals from the bar code requirement because existing NRC
regulations on the medical use of radiation byproducts render the bar
code unnecessary for patient safety.
Section 201.25(d)(2) provides the address to which exemption
requests should be sent. For human drug products, the request should be
sent to the Office of New Drugs (HFD-020), Center for Drug Evaluation
and Research, Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857. For biological products, the request should be
sent to the Office of Compliance and Biologics Quality (HFM-600),
Center for Biologics Evaluation and Research, Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852.
We reiterate that we have created this general exemption provision
to allow us to efficiently and justly address products or classes of
products that we have not already considered. We emphasize that almost
all drug products are capable of bearing, and should in fact bear, a
bar code. We will not consider written requests that are based on other
reasons (such as financial reasons, a claimed low rate of medication
errors, or a claim that the product is somehow unique such that
medication errors do not occur or rarely occur). Similarly, we will not
entertain written requests seeking an exemption for a particular drug,
class of drugs, or group of products when we have already refused to
grant an exemption for the same drug, class of drugs, or group of
products in this final rule. The general exemption provision is
intended to be used in rare cases.
If we refuse to grant an exemption in response to a written
request, our decision can be reviewed under our existing regulation at
21 CFR 10.75, ``Internal agency review of decisions.''
5. Should Medical Devices Be Excluded From the Rule?
The preamble to the March 2003 proposal explained that we did not
intend to issue any bar code requirement for medical devices at this
time (see 68 FR 12500 at 12506). The preamble to the March 2003
proposal stated that devices present different issues compared to human
drug and biological products and that we would continue to study
whether to develop a proposed rule to require bar codes on
[[Page 9132]]
medical devices to prevent or reduce medication errors (id.).
(Comment 29) Two comments said we should reject the device
industry's request for further study and require bar codes on devices.
The comments said that implantable devices are made to detailed
specifications and sometimes fail, so one could presume that a device
manufacturer would recall defective devices. The comments added that
bar codes on devices would help create patient records that could be
easily searched so that hospitals could determine an appropriate course
of action if a patient received an implantable device that was
recalled.
Other comments argued that we should examine the benefits of bar
code labeling on devices or that bar codes would be helpful on certain
devices. For example, one comment said that patient safety would be
further enhanced by applying bar codes to devices such as blood bags,
filters, and apheresis kits.
Conversely, one comment agreed with our decision to omit devices
from the rule. The comment said that devices present ``unique'' issues,
such as product diversity, evolving coding technology, and unique
product identification needs that are often negotiated between
customers and device manufacturers. The comment recommended that we
allow for voluntary use of Universal Product Numbers (UPNs) on devices
in either the European Article Number/Uniform Code Council (EAN/UCC) or
Health Industry Business Communications Council (HIBCC) standard. The
comment explained that the UPN system is established and provides
greater consistency with global identification trends compared to the
NDC number.
(Response) We decline to include devices in the final rule. Unlike
drugs, medical devices do not have a standardized, unique identifying
system comparable to the NDC number. (There is a National Health
Related Items Code (NHRIC) system for identifying and numbering
marketed medical device packages, but participation in the NHRIC system
is voluntary, and the database may contain out-of-date information due
to industry acquisitions and mergers.) The absence of a standard,
numerical identification system comparable to the NDC number is one of
several issues that complicate efforts to put bar codes on medical
devices for purposes of preventing or reducing medication errors.
We also note that permanently implantable devices are subject to
our device tracking requirements at part 821 (21 CFR part 821), and
those requirements can be quite detailed. For example, under Sec.
821.25(a)(2)(iii), a device manufacturer must have a method of tracking
each device that it distributes that enables the manufacturer to give
FDA, within 10 working days of a request from FDA, information
regarding the name, address, telephone number, and social security
number (if available) of the patient receiving the device.
As for voluntary use of UPNs on medical devices and the use of
EAN.UCC or HIBCC standards, we recognize that some devices already bear
a bar code for reasons relating to purchasing or inventory control, and
we have not objected to their use nor to the bar code standards used.
C. What Must the Bar Code Contain? (Sec. 201.25(c)(1))
1. Should We Require the Bar Code to Contain the NDC Number?
Proposed Sec. 201.25(c)(1) would require the bar code to contain,
at a minimum, the drug's NDC number. The NDC number identifies each
drug product that is listed under section 510 of the act or section 351
of the PHS Act.
(Comment 30) Two comments claimed that their products, allergenic
extracts, do not have NDC numbers. The comments stated, as part of a
request to have allergenic extracts excluded from the rule, that FDA
has allowed generic groupings for allergens under one NDC number. The
comments added that they market nearly 200 to 300 allergens in four
different package configurations each, so, if allergenic extracts had
to carry bar codes, the firms would need from 800 to 1,200 new NDC
numbers respectively, and this would have ``enormous'' implications for
the firms and FDA.
(Response) As we stated in our response to comment 15 in section
II.B.4.b of this document, we have excluded allergenic extracts from
the rule. As a result, issues regarding NDC numbers for allergenic
extracts are moot.
(Comment 31) Several comments focused on the NDC number itself. One
comment said that the NDC number contains the necessary information for
bar code purposes. However, several comments argued that OTC drug
products should be allowed to use the Universal Product Code (UPC)
number either instead of or in addition to the NDC number. Some
comments said that OTC drug manufacturers would incur thousands of
dollars of ``unnecessary extra `new item' costs'' because different NDC
numbers would be necessary for new, minor formulation changes to their
drugs and create logistical complications for retailers (because
retailers use the UPC codes). Two comments said that requiring OTC drug
bar codes to contain the NDC number would increase the demand on NDC
numbers, increase FDA's workload, or exhaust the number of available
NDC numbers. One comment said it should be feasible for a database to
handle both NDC and UPC numbers, whereas another comment said that
allowing OTC drug products to continue using UPC numbers would make
more NDC numbers available for other drug products and thus benefit the
NDC number system.
Another comment supported the use of the NDC number with four extra
digits. The comment said this 15-digit number, called ``NDC Plus
Four,'' would identify individual doses and vital information about the
drug, including, among other things, the drug's lot number, expiration
date, and recall status.
Another comment asked us to change the NDC number so that it
contained a drug's expiration date.
(Response) We decline to amend the rule as suggested by the
comments. The UPC code does not necessarily identify a unique drug
product. For example, if an OTC drug manufacturer made and sold a
particular drug product, that drug product would have a UPC code, and
it would also have a unique NDC number. If the OTC drug manufacturer
reformulated the product (such as changing an ingredient), the
manufacturer could use the same UPC code for the reformulated product,
but the reformulated drug would have a different, unique NDC number.
This could be significant to a patient's health if, for example, the
reformulated product contained an ingredient that caused allergic
reactions or drug interactions. Thus, requiring the use of NDC numbers,
rather than UPC numbers, will help ensure that the drug is identified
correctly.
Additionally, as we stated in the preamble to the March 2003
proposal (see 68 FR 12500 at 12507), we intend, through a separate
rulemaking, to change the NDC number so that it becomes a unique
identifying number for listed drugs. If we were to allow the use of
other coding systems, such as UPC numbers that did not contain the
drug's NDC number or an NDC number with additional digits, persons who
wanted to decipher a drug's bar code would need to consult multiple
information sources, and this would increase the likelihood that some
information and databases might not be updated as frequently as others,
that
[[Page 9133]]
some information might be unavailable, or that the information would be
presented in different or incompatible ways. Although we understand the
OTC drug industry's reservations about changing UPC codes to include
NDC numbers because of a possible cost impact, Sec. 201.25(b) only
requires bar codes on OTC drug products that are dispensed under an
order and are commonly used in hospitals. Furthermore, as we stated in
our response to comment 9 of this document, we will allow OTC drug
manufacturers to create bar coded and nonbar coded versions of the same
OTC drug product; the bar coded versions, which would be intended for
hospital sale and use, would carry the NDC number in the bar code. The
versions intended for retail sale could continue to use the UPC code.
We also decline to revise the NDC number to include expiration
dates or to add more digits to the NDC number. Revising the NDC number
is outside the scope of this rule. Furthermore, expiration dates vary
with each new batch or production run, so if we were to revise the NDC
number to include expiration dates, we would quickly exhaust the number
of available NDC numbers and be forced either to redefine the NDC
number or develop an alternative system relatively quickly, and other
databases that relied on the NDC number would also be forced to adapt
or develop new systems themselves. Restructuring the NDC number in this
manner would, therefore, be impractical and costly.
Similarly, adding more digits to the NDC number might be disruptive
for those databases that already use or rely upon the NDC number. Those
databases would either have to reconfigure themselves to handle 14-
digit numbers (assuming all preexisting NDC numbers were modified to
contain 14 digits) or reconfigure themselves to handle 10- and 14-digit
NDC numbers (assuming that preexisting NDC numbers remained the same,
but new drugs would receive a 14-digit number). Such reconfigurations
could be expensive for those who maintain the databases and those who
use them. A 14-digit number could also be either redundant or confusing
in comparison to the Global Trade Item Number (GTIN). As the preamble
to the March 2003 proposal mentioned, the GTIN is a 14-digit number
which, when used in a bar code on drug products, contains the NDC
number in conjunction with a code that identifies the product's packing
level (see 68 FR 12500 at 12506).
(Comment 32) Two comments asked us to ensure that different parties
use different NDC numbers. One comment said that the proposed rule
failed to explain how repackers will distinguish a repacked product
from the original manufacturer's package. The comment suggested that
manufacturers use certain digits to signal the presence of an original
manufacturer's package and that repackers use other digits to identify
repackaged products. The comment said we should require repackers to
have a manufacturer's identification number.
The other comment asked that we ensure that hospitals do not use
the manufacturer's NDC codes when repacking a drug.
(Response) As we stated in our response to comment 2 of this
document, if a repacker, relabeler, or private label distributor is
subject to the establishment registration requirement at section 510 of
the act, then that person is also subject to the bar code requirements
and must use its own NDC numbers on its products. In other words, a
manufacturer, repacker, relabeler, or private label distributor cannot
and should not use an NDC number that is not assigned to it. Use of
another establishment's NDC number in the bar code would cause the
product to be misbranded under section 502(a) of the act because the
drug's label would be misleading.
Hospitals, though, are exempt from the establishment registration
requirements. Consequently, hospitals themselves are not subject to the
bar code requirement, and we consider drug repacking and dispensing
operations inside hospitals to be within the practice of pharmacy.
(Comment 33) Several comments addressed possible changes to the NDC
number. The preamble to the proposed rule stated that we intended to
redefine the NDC number through a proposed rule on drug establishment
registration and listing (see 68 FR 12500 at 12506). Most comments
opposed any redefinition of the NDC number. One comment said that
redefining the NDC number would create confusion, possibly harm
patients (although the comment did not explain how such harm would
occur), and undermine the bar code rule. Other comments said that
redefining the NDC number would be costly and disruptive to various
databases that rely on or use NDC numbers. One comment said that we
should not make a final bar code rule effective until the drug industry
has had the opportunity to understand and comment on any changes to the
NDC number. A different comment said we should consult various
``stakeholders'' before we make changes to the NDC number. Another
comment said that we did not need to redefine the NDC number because
the GTIN would provide ``sufficient direction.''
(Response) As we stated in the preamble to the March 2003 proposal,
we intend to revise our drug establishment registration and listing
regulations to make the NDC number unique and more useful to
informational databases, whether those databases are created to prevent
medication errors, to obtain the latest information about a drug, or to
track drug use and distribution. We are still preparing the proposed
rule, and when we publish it in the Federal Register, we will invite
comment on our proposed NDC number changes. Until we revise our drug
establishment registration and listing regulations, the current
requirements at Sec. 207.35 continue to apply to the NDC number.
We also must point out that, even under a proposed drug
establishment registration and listing rule, assuming there is no
change in the product or packaging, we do not intend to replace
currently-used NDC numbers. For existing NDC numbers, we would consider
issuing a new number to an existing drug product only if there were two
drugs that had the same NDC number.
(Comment 34) One comment criticized the NDC number, stating that it
cannot tell whether the right dose is being administered because the
actual dose may be a partial dose or multiple doses of the drug
identified by the bar code. The comment said this reflected a
technological limitation with NDC numbers, so the comment suggested
that the computer systems used to document drug administration alert
users and require manual intervention by health care professionals to
verify doses.
(Response) The comment is correct that the NDC number may have
certain limitations when different dosages are administered from a
single package or when partial dosages are administered. For example,
assume that a drug's package contains 20 tablets. The drug's NDC number
will reflect the fact that the package contains 20 tablets. If the drug
administered to the patient consists only of one tablet, then scanning
the NDC number for the package alone will not show the correct dose
given to the patient. The NDC number's principal value, in this
scenario, is verifying that the correct drug in the correct dosage form
is being administered. As another example, some drug product labels do
not state pediatric dosages, so a physician might prescribe a partial
dose for a pediatric patient. In this scenario, the NDC
[[Page 9134]]
number's principal value is verifying that the correct drug, in the
correct dosage form, is being administered.
Regarding the comment's suggestions concerning computer systems, we
agree that it could be helpful if a computerized database alerted
health care professionals to check dosages given to patients. However,
we do not intend to create, maintain, or regulate the databases that
scanning equipment would consult to decode NDC numbers, so we advise
parties to consider this issue when they develop computer systems
associated with scanners to decode the NDC numbers.
2. Should the Bar Code Contain Lot Number and Expiration Date
Information?
The March 2003 proposal would not require the bar code to contain
the drug's lot number or expiration date. In the preamble to the March
2003 proposal, we explained that we were unable to show that the
benefits associated with encoding lot number and expiration date
information exceeded the costs, so we proposed to omit lot number and
expiration date information from the bar code (see 68 FR 12500 at
12507). However, we also said that we would not object if drug
manufacturers, repackers, relabelers, and private label distributors
decided to encode lot number and expiration date information
voluntarily (id. at 12508). We stated that industry representatives had
suggested that they might add such information if a demand existed for
it (id.), but we did not know whether hospitals and other health care
facilities would be willing to pay more for drugs that had lot number
and expiration date information encoded in the bar code. We invited
comment on the costs and benefits associated with putting lot number
and expiration date information in the bar code.
(Comment 35) Many comments urged us to require lot number and
expiration date information in the bar code, but did not provide
evidence to support their views. Instead, most comments declared that
lot number and expiration date information would make it easier to
identify recalled, contaminated, and expired drugs, would improve
entries into medical records, or would provide greater patient safety.
Other comments said we should phase-in a requirement to encode lot
number and expiration date information over an extended time period,
but did not discuss why a phased-in approach would alter the cost-
benefit problem that we identified in the preamble to the proposed
rule. Some comments would extend the rule's effective date to give
firms more time to encode such information. Another comment urged firms
to encode lot number and expiration date information, but only if the
costs were not passed on to hospitals.
Other comments advanced different arguments for requiring lot
number and expiration date information as part of a bar code. For
example, one comment stated that the American Society of Hospital
Pharmacists and others want lot number and expiration date information
encoded, and so we should defer to them. Several comments said
manufacturers should encode such information because they could do so
at less cost compared to hospitals.
Several comments advocating the inclusion of lot number and
expiration date information in a bar code argued that technology could
encode such information. For example, one comment claimed that the
information can be easily encoded using two-dimensional symbologies and
noted that some manufacturers plan to encode such information
voluntarily. Another comment noted that the GTIN, rather than the NDC
number alone, could be used to provide additional patient safety
information. Another comment declared that encoding lot number and
expiration date information could be inexpensive because, the comment
noted, firms already print the same information, in human-readable
form, on packages.
In contrast, other comments supported our decision to omit lot
number and expiration date information from the rule. Several comments
conceded that the information could help trace recalled drugs and help
with product inventory, but said that the information would not
significantly reduce medication errors and that the costs of encoding
the information would exceed the benefits. For example, one comment
estimated that encoding lot number and expiration date information
would cost $7,500 to $20,000 per manufacturer's line, excluding costs
to verify the information. Several comments expressed concerns about
the impact on production line speed. For example, one comment said that
the online printing equipment that would be needed for encoding lot
number and expiration date information is ``highly ineffective and
unreliable'' at production speeds above 120 units per minute and that
alternatives, such as preprinting labels, would present serious good
manufacturing practice (GMP) concerns in verifying that the right label
with the correct lot number and expiration date is used on the correct
product. Another comment said that online printing and verification
technology has not been demonstrated at production line speeds of 250
to 300 units per minute. A different comment listed various problems
associated with online printing of lot number and expiration date
information, such as adverse impacts on line speed and print quality,
the need to develop unique bar codes for each packaging run, and
limiting packaging options until printing and packaging technology
becomes capable of supporting online product speeds and adequate print
quality.
Another comment said we were correct to omit lot number and
expiration date information from the rule because it would make bar
coding more complex and perhaps discourage manufacturers from making
unit-dose packages. The comment, along with other comments opposed to
requiring lot numbers and expiration dates in a bar code, shared our
view that the market would determine whether manufacturers and others
encode lot number and expiration date information voluntarily.
One comment suggested that, if we decide to require lot number and
expiration date information to be encoded, the information should only
go on shipping cartons and not on individual packages because this
would reduce the manufacturer's costs.
The comments also disagreed on how to interpret our recall data.
The preamble to the proposed rule stated that we had examined the
number of recalled drugs from fiscal year 1997 through fiscal year 2002
and that, while there were 1,230 recalls during that time period, there
were few reports of adverse experiences associated with the
administration of a recalled drug (see 68 FR 12500 at 12507). One
comment said this data supported inclusion of lot number and expiration
date information in the bar code because Class I recalls represent a
reasonable probability that the use or exposure to the drug will cause
serious adverse health consequences or death, and 97 of the 1,230
recalls were Class I recalls. In contrast, a comment that opposed
inclusion of lot number and expiration date information in the bar code
said the data were not sufficient to show any public health problem
resulting from the administration of recalled or expired drugs.
(Response) The final rule does not require lot number or expiration
date information to be included in the bar code. As we stated in the
preamble to the March 2003 proposal, the data available to us do not
indicate the magnitude of the public health problem associated with
administering expired or recalled drugs, and we cannot
[[Page 9135]]
quantify the patient safety benefit associated with requiring lot
number and expiration date information in the bar code (see 68 FR 12500
at 12507). The potential burden of encoding lot number and expiration
date information appears to outweigh the potential benefit of encoding
such information.
We emphasize that we do not dispute whether encoded lot number and
expiration date information would be helpful in certain contexts that
are unrelated to medication errors. We also do not dispute that the
technology exists to encode such information or that certain firms have
expressed their intent to encode such information. Nevertheless, while
we recognize the strong desires expressed by some regarding lot number
and expiration date information, we must also recognize the potential
impact on manufacturers, repackers, relabelers, and private label
distributors if we required them to encode lot number and expiration
date information. The evidence before us indicates that the costs
associated with encoding lot number and expiration date information,
insofar as medication errors are concerned, exceed the benefits, so we
decline to require such information as part of the bar code.
We reiterate that we will not prevent or prohibit firms from
encoding lot number and expiration date information if they wish to do
so, and we note that some drug manufacturers are encoding or intend to
encode such information. We also remind hospitals and other potential
bar code users that lot number and expiration date information may be
encoded in two-dimensional or other technologies, so if they intend to
purchase drug products with lot number and expiration date information
encoded, they should consider carefully their scanning or reading
equipment purchases (see 68 FR 12500 at 12507).
(Comment 36) Several comments would require other information to be
encoded. For example, one comment said we should require the bar code
to contain information regarding the drug's concentration, amount, and
route of administration. The comment explained that information on the
drug's concentration and amount could prevent errors involving
concentration or overdose. It explained that information regarding the
drug's route of administration could be helpful because, the comment
claimed, some drugs are not to be administered intravenously or as
major nerve anesthetics. Another comment focused on clotting factor
products and wanted the bar code for these products to contain (among
other things) the drug's brand name and number of units in a vial. The
comment recognized that encoding the number of units in a vial might be
difficult, but said that persons with hemophilia and other bleeding
disorders often carry vials, but not package boxes that contained the
vials, with them. It added that the additional information would
provide better information about the product's efficacy, i.e., whether
the patient achieved the expected hemostatic response given the units
administered.
Several comments asked that we require the bar code to indicate the
drug's waste disposal status under the Resource Conservation and
Recovery Act (RCRA). The comments explained that medical personnel
might not know that a particular drug, when it becomes a waste product,
is regulated under RCRA. Some comments suggested that the drug's waste
disposal status could be identified by adding another digit to the NDC
number. One comment suggested that we coordinate with the Environmental
Protection Agency to capture a drug's hazardous waste disposal status.
(Response) We decline to revise the rule as suggested by the
comments. The NDC number, under a bar code system, is a link to
information held in a database. For example, assume that the bar code
contains the drug's NDC number. The scanner reading the bar code would
transmit the NDC number to a computerized database, and that database
could be designed to generate information regarding the drug's names,
dose, concentration, route of administration, waste disposal status,
etc. In other words, the information sought by the comments could be
built into a database and does not have to be encoded in the bar code
itself and does not require changes to the NDC number.
3. Can Information Be Omitted From the Label to Accommodate the Bar
Code?
(Comment 37) Several comments suggested that we allow firms to
exclude certain information from their labels so that they could affix
a bar code. Some comments sought relief from the labeling requirements
at Sec. 201.10(i) (21 CFR 201.10(i)); that provision requires drug
labels to contain the drug's proprietary name, established name (if one
exists), an identifying lot or control number, and the manufacturer's,
packer's, labeler's, or distributor's name. One comment suggested
amending Sec. 201.25(c), regarding the bar code's placement on a
label, to state that any drug complying with the bar code requirement
is exempt from Sec. 201.10(i)(1)(iii) and (i)(1)(iv) (provisions
regarding the identifying lot number or control number and
manufacturer's, packer's, labeler's, or distributor's name) if the
packaging size is such that the required information is not easily
readable.
One comment sought clarification regarding a label requirement
imposed by another Federal agency. The comment claimed that the
Consumer Product Safety Commission (CPSC) has a regulation that
requires drug products labeled for hospital use only to also bear a
statement regarding use in households without young children.
Several comments focused on small labels. One comment stated that
excluding ``some'' label information would help print high quality bar
codes; the comment identified the manufacturer's or distributor's name
and address as information that it would exclude from a label.
Similarly, another comment would remove the manufacturer's name from
the label because, the comment explained, the manufacturer's name is on
the outer package and is part of the NDC number. Another comment stated
that the only way to create room for a bar code on a small label would
be to reduce font size, but the resulting print would be difficult to
read.
(Response) We decline to amend the rule as suggested by the
comments. In most cases, the information that the comments would remove
from the label is required by Federal law, so we are unable to provide
the relief sought by the comments. For example, section 502(b)(1) of
the act considers a drug to be misbranded if it is in package form and
its label does not contain ``the name and place of business of the
manufacturer, packer, or distributor.'' Section 502(b) of the act does
not authorize any exemptions from this requirement, so we cannot delete
such information from the label simply to accommodate a bar code.
Similarly, section 502(e)(1)(A)(i) of the act considers a drug to be
misbranded if its label does not bear the drug's established name, so
we cannot allow firms to exclude the drug's established name from the
label. Additionally, section 351(a)(1)(B) of the PHS Act requires the
package of a biological product to be marked with the product's proper
name, the name, address, and applicable license number of the product's
manufacturer, and the product's expiration date.
Furthermore, because the rule does not require lot number and
expiration date information to be encoded, we decline to allow firms to
remove the human-readable lot number and expiration date information
from the label.
[[Page 9136]]
As for the comment seeking clarification of CPSC requirements, such
matters are outside the scope of this rule and outside FDA's
jurisdiction.
D. Does the Rule Require a Specific Type of Bar Code? (Sec.
201.25(c)(1))
1. Should the Rule Require Linear Bar Codes?
Proposed Sec. 201.25(c)(1) would require the bar code to be a
linear bar code that meets EAN/UCC standards. The preamble to the March
2003 proposal discussed, in some detail, how we decided to propose the
use of linear bar codes and described the tension between trying to
create a bar code requirement that would enable hospitals to buy
scanning equipment with the confidence that their purchased equipment
would not be rendered obsolete by new technology and trying to create a
bar code requirement that offered some room for technological
innovation (see 68 FR 12500 at 12508 through 12510). We also invited
comment on whether we should consider the use of another symbol,
standard, or technology, either with or in place of a linear bar code,
the acceptance of that other symbol, standard, or technology among
parties that would be subject to the rule, and the ability of hospitals
to read or use other symbols, standards, or technologies (id. at 12510
and 12529).
(Comment 38) Many comments addressed the subject of linear bar
codes. Several comments indicated the rule should require the use of
linear bar codes because of their widespread use and because hospitals
that are currently printing and scanning bar codes might be unable to
upgrade their technology to support nonlinear technologies. One comment
stated that our decision to require linear bar codes was ``brilliant''
and that our logic was ``impeccable.'' Another comment said that linear
bar codes could be used as an initial requirement and that technology
currently installed in most hospitals cannot be upgraded to support
nonlinear technologies. The comment added that if we required nonlinear
bar codes, hospitals could face significant costs, and those hospitals
that had already implemented linear bar code systems would be
penalized. Another comment said that many applications of currently-
used linear bar code systems are appropriate for suppliers and end
users. The comment, which was submitted by a supply company for two
large, not-for-profit hospital alliances, added that it shared our
concern that ``technologies/standards not be so advanced that hospitals
are then unable to read and scan the bar codes,'' and it urged us to
evaluate and promote new and emerging technologies ``only as they
become more readily available, and easily embraced by end users.''
Another comment said we should require the bar code to meet certain
``attributes;'' the comment explained that this would provide some
flexibility (although it did not explain what the attributes would be
or what that flexibility was) while still ensuring a minimum standard.
The comment added that the standard should be one that does not require
hospitals to spend significant amounts of money to replace scanning
equipment that would otherwise be acceptable for use. Two comments
submitted by drug manufacturers expressed a similar opinion, stating
that we should allow firms to use any linear bar code symbology so that
firms could pick the symbology that best fits their needs.
One comment agreed with our proposal to require linear bar codes,
but asked whether this included multidimensional codes. The comment
claimed that multidimensional codes are several thinly-stacked linear
codes. It added that, while older bar code scanners might not be able
to read multidimensional codes, we should not be concerned about older
scanners because most hospitals would not have scanners (and therefore
would not need upgrades) or that hospitals with older scanners could
upgrade those scanners.
Most comments, however, argued against the use of linear bar codes
or asked us to encompass other technologies or to eliminate any
reference to linear bar codes in the final rule. Many comments claimed
that the rule would discourage or inhibit technological innovation,
although they differed as to their preferred alternatives to a linear
bar code. For example, one comment said laws and regulations should
encourage technological innovation, but did not explain why our
particular rule had to do so. Comments opposed to a linear bar code
requirement generally advocated the following alternatives:
[sbull] Two-dimensional symbologies, on the grounds that such
symbologies can be used on small packages, require less space compared
to linear bar codes, can encode more data than a linear bar code
(although the comments usually did not explain why more data capacity
was needed), or can be placed on solid dosage forms themselves. Some
comments specifically mentioned DataMatrix as a recommended symbology,
whereas others referred to symbols or systems created or marketed by
the firm who submitted the comment or to symbols that would be marketed
in addition to the two-dimensional symbology. Other comments suggested
using two-dimensional symbologies in conjunction with linear bar codes,
with the two-dimensional symbology encoding lot number and expiration
date information.
[sbull] The EAN/UCC system generally, on the grounds that the EAN/
UCC system is widely used for drug products, has defined data
structures, is used internationally, and would be less expensive
compared to a regulatory approach that imposed no standard. However,
other comments opposed the EAN/UCC system, declaring it to be
``obsolete,'' or declaring that selecting the EAN/UCC would serve no
purpose, would violate unspecified Federal laws, or would create a
``monopoly'' for the UCC. (We discuss comments on the EAN/UCC standard
and HIBCC standards in more detail in comment 41 of this document.)
[sbull] Radio frequency identification chips. Some comments
advocated the use of these chips and claimed that such chips could be
an alternative to or used with the bar code and can be ``highly
effective'' at identifying individuals and animals in a cost-effective
manner. One comment noted that we had mentioned the comparatively high
costs associated with radio frequency identification chips, but said we
should not reject the chips on cost grounds alone. It said the
pharmaceutical industry and health care providers should have the
flexibility to choose identification techniques that are the most
suited to a product or clinical setting. The comment added that if we
required the use of a particular technology, we would create a conflict
with our GMP principles because our GMP regulations do not require use
of a particular piece of equipment, and we would be creating a
disincentive for industry to develop more cost-effective identification
systems.
[sbull] No standard or symbology at all. These comments advocated
the use of ``open'' or ``machine-readable'' requirements so that market
forces would decide which technologies would be used. One comment added
that the use of nonlinear codes would make linear bar codes
technologically obsolete by the time the final rule became effective.
Another comment said we should require ``automatic identification''
instead of bar codes. Another comment suggested that manufacturers,
repackers, and relabelers be allowed to customize symbols to meet
customer needs, although the comment did agree that the NDC n