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11 LABELING
LABELING REGULATIONS
Misbranding
False or Misleading Labeling
Adequate Directions for Use
Prescription Devices
Sterile Devices
DESIGN OF LABELING
Write to the Reader
Refer to Actual Device
Obvious Identification of Controls
Don't Distract Reader
Short and to the Point
Gobbledygook
Introduce Each Item
Accentuate Key Terms
Select Words Wisely
Test Labeling
Label Integrity
Approval Policy and Procedure
Design Transfer
Production Controls
Receipt and Inspection
Area Separation and Inspection
STORAGE
Label Check and Record
Control Numbers
Access Restriction
CHANGES
SHIPPING FOR PROCESSING
OVERLABELING
EXHIBITS
Drafting and Approval of Labeling
Approval Form for Labeling, Advertising,
Literature, etc.
Administration Set Label
Labeling Control Record
Device History Record: OB/GYN (Plate)
User/Reader Comments
Medical devices in commercial distribution in the U.S. shall be
properly labeled according to laws and regulations enforced by
the Food and Drug Administration (FDA). Specific labeling requirements
for medical devices are contained in:
Section 201(k) of the FD&C Act defines the term "label"
as "a display of written, printed, or graphic matter upon
the immediate container of any article . . . ." Under Section
201(l) of the FD and C Act, the term "immediate container"
does not include a package liner. Any word, statement, or other
information appearing on the immediate container should also appear
on the outside container or wrapper, if any, of the retail package
or be easily legible through the outside container or wrapper.
The label is not required to appear on the shipping carton.
Section 201(m) of the FD&C Act defines the term "labeling"
as all labels and other written, printed, or graphic matter: (1)
on the device or any of its containers or wrappers, or (2) accompanying
the device. The term applies any time while the article is in
interstate commerce, or being held for sale after shipment or
delivery in interstate commerce. The term "accompanied"
is interpreted liberally. It extends to posters, tags, pamphlets,
circulars, booklets, direction sheets, fillers, etc., that may
be displayed in proximity to the article or shipped to the user
before or after shipment of the device.
The distinction between labeling and advertising, while both draw
attention to the article to be sold, is often nebulous or superficial.
Both are forms of publicity and are used for an identical purpose.
An appellate court described the relationship between the two
as follows: "Most, if not all, labeling is advertising. The
term 'labeling' is defined in the Act [section 201(m)] as including
all printed matter accompanying any article. Congress did not,
and we cannot, exclude from this definition printed matter which
constitutes advertising."
Section 502(f)(1) and (2) of the FD&C Act requires that device
labeling bear adequate directions for use, operating and servicing
instructions, and either adequate warnings against uses dangerous
to health, or information necessary for the protection of users.
All devices require directions for use unless specifically exempted
by regulation. Conditions for exemption from this requirement
are in 21 CFR 801, Subpart D.
Misbranding
Section 502 of the FD&C Act contains the misbranding provisions
for drugs and devices. It states a device is misbranded under
a number of different circumstances, including:
The Medical Device Amendments expanded the authority of the FD&C
Act over misbranded medical devices. These amendments contain
further circumstances under which a device is misbranded:
False or Misleading Labeling
Section 502(a) states that a drug or device is misbranded if its labeling proves false or misleading in any particular. It is not a necessary condition that the labeling should be flatly and blatantly false for the FDA to take action. The word "misleading" in the FD&C Act means that labeling is deceptive if it creates or leads to a false impression in the mind of a reader. A "false impression" may result not only from a false or deceptive statement, but may be instilled in the mind of the purchaser by ambiguity and indirection. It might be caused by failure to inform the consumer of facts that are relevant to those statements actually made. In other words, the label that remains silent as to certain consequences may be as deceptive as the label that contains extravagant claims. Examples of misleading labeling include: ambiguity; half truths; trade puffery; expressions of opinion or subjective statements; and failure to reveal material facts, consequences that may result from use, or the existence of difference of opinion.
In the past, labeling found by the agency to be objectionable
has featured such practices as: deceptive pictorial matter; misleading
testimonials; misleading lists of parts or components; and brand
or trade names instead of "established names" (see Sections
201(h), 502(e)(2), and 508 of the FD&C Act). Examples of false
representations are:
Adequate Directions for Use
Title 21, CFR Part 801.5, defines "adequate directions for
use" as "directions under which the layman can use a
device safely and for the purpose for which it is intended."
See Part 801.4 for a definition of "intended use."
Among other reasons, directions for use may be inadequate because
there is partial or total omission or incorrect specification
of one or more of the following items:
Prescription Devices
Labeling exemptions for prescription devices are in 21 CFR Part
801.109. These are devices which because of a potential for harmful
effect, potential for misuse, or the collateral measures necessary
to use, are not safe except under the supervision of a practitioner
licensed by law. Hence "adequate directions for use"
cannot be prepared for these devices. They are exempt from Section
502(f)(1) of the FD&C Act provided that all conditions specified
in the labeling regulation are met.
These conditions state that the device shall be in the possession
of a person, or his or her agents, or employees regularly and
lawfully engaged in the manufacture, transportation, storage,
or wholesale distribution of prescription devices; or in the possession
of a practitioner such as a physician, dentist, or veterinarian
licensed by law to use or order the use of these devices. These
devices can be sold only to, on the prescription of, or by order
of such practitioner for use in the course of their professional
practice.
The label of the prescription device, other than surgical instruments,
is required to bear:
Labeling on or within the package from which the device is to
be dispensed shall also bear information for use under which practitioners
licensed by law to administer the device can use the device safely
and for the purposes for which it is advertised or represented.
This labeling information includes indications, effects, dosages,
routes, methods, frequency, and duration. Safety labeling includes
relevant information on hazards, contraindications, side effects,
and precautions.
When a device is capable of producing serious injury, even when
used by a person thoroughly familiar with its operation, the directions
for use shall provide detailed information. FDA has specific regulations
on the labeling of intrauterine contraceptive devices, 21 CFR
801.427, and for diagnostic xray devices, 21 CFR 1020.30(h).
In addition, FDA has issued general guidances for labeling certain
devices, i.e., transcutaneous electrical nerve stimulators and
electronic muscle simulators.
Where appropriate, directions for use should be supplemented with
adequate warnings against the use of the drug or device under
certain conditions. Any caution statement, similar to the directions
statement, may appear in the labeling of the product; it is not
necessary that it be printed on the label. In each instance, the
responsibility for the adequacy of the warning statement appearing
on the labeling rests with the manufacturer or distributor. For
some devices, there are national consensus standards that specify
that certain caution statements be on the device. There is no
list of prescription devices in the CFR.
Sterile Devices
Special attention should be given to the labeling of sterile devices.
For example, sterility may be needed only for a portion of certain
devices and this condition should clearly be identified in the
labeling. Devices that are not sterile in their entirety should
be labeled to properly inform users what is actually intended
to be "sterile" in the package. For example, a possible
limiting statement might be:
"Caution: Only the fluid path of this set is sterile
and nonpyrogenic. Do not use in a sterile or aseptic area without
proper precautions."
The label of multidevice kits or packages containing a combination
of sterile and nonsterile products will be considered to be false
or misleading if it implies that all contents are sterile.
Some devices are intended to be sterilized by the user before
use. In this situation, the labeling should provide adequate information
about a suitable method of sterilization and any precautions or
safeguards to be followed. For example, the labeling should describe
any:
In the case of singleuse sterile devices, many manufacturers
include labeling to advise against resterilization and reuse.
Some devices are not designed or constructed to be recleaned,
and may not be capable of withstanding the necessary recleaning
and resterilization procedures. Where reuse is common practice,
manufacturers are encouraged to provide the information described
in the above list.
The need for users to have instructions on how to open a sterile
device package to avoid contamination of the device also needs
to be evaluated. When necessary, such instructions should be included
in the labeling.
If a manufacturer modifies a device, the manufacturer should also
review the labeling to ensure that it reflects current revisions
and specifications. Thus, change control forms should contain
a check off box for labeling and packaging. Some manufacturers
identify labeling with a drawing number plus a revision code or
date as an aid in identifying current labeling. The package insert
or other labeling for in vitro diagnostic products is required
to contain the revision date [21 CFR 809.10(b)(15)].
Shelflife dating solely for package integrity and sterility
is not usually required for general medical devices. There may
be a need for expiration dating when a particular component of
a device, such as a battery or diagnostic reagent, has a finite
useful life. Labeling for in vitro diagnostic devices [809.10
(a) and (b)] requires an expiration date or some other means by
which users may be assured of quality at the time of use. This
requirement applies to both sterile and nonsterile in vitro diagnostic
devices.
Although not required by regulation, most manufacturers of complex
devices and sterile devices voluntarily use lot or serial numbers
for production control and, if the need arises, to expedite failure
investigations, repairs, modifications, or recalls. Lot, batch,
or other control numbers are required for:
Various sections of the Quality System (QS) regulation have an
impact on labeling including: section 820.30, Design controls;
section 820.80, Receiving, in-process, and finished device acceptance;
and section 820.70(f), Production and Process controls, which
requires buildings to be of suitable design and have sufficient
space for packaging and labeling operations. Section 820.120 deals
with specific requirements for device labeling. These sections
apply controls to the labeling content to meet the needs of the
user and patient, as well as to meet the labeling specifications
contained in the device master record. Applying the regulations
to the physical design applications of labeling assures legibility
under normal conditions of use over the expected life of the device.
It also helps assure the proper inspection, handling, storage,
and distribution of labeling. The requirements in 820.30(c), Design
input, address the intended use of the device, and the needs of
the user and patient.
Labeling includes equipment labels, control labels, package labels,
directions for use, maintenance manuals, etc. The displays on
CRTs and other electronic message panels are considered labeling
if instructions, prompts, cautions, or parameter identification
information are given.
Adequate labeling for a medical device requires proper design
and procurement of the labels and labeling. Design includes generating
the content of labels and labeling and making sure the content
meets FDA requirements as well as the needs of the customer. To
achieve these goals a number of concepts must be kept in mind
such as: writing to the reader, referring to the actual device
in labeling, obvious identification of the controls used, etc.
Design controls for label integrity are discussed later.
There are some basic guidances, rules, and practices that can
be used to immediately improve writing. The following paragraphs
will discuss them, with emphasis on how they can be used to make
labeling clear and comprehensible.
As an essential aid, writers are encouraged to obtain a copy of
40,000 Words published by Webster's New World Dictionary
or a similarly titled book by any of the referencebook publishing
companies. Most of these reference books have about four pages
of punctuation rules. Using these pages of rules can immediately
improve not only the style and clarity but also the accuracy of
your writing. Writers are also encouraged to obtain and use a
standard collegelevel text on technical writing.
Write to the Reader
The most serious problem is that writers tend to write to themselves.
Their material is clear to them so they mistakenly think it is
as clear to others. For example, the sensitivity control on an
instrument is called "gain" control on page one of the
instruction manual, "amplitude" control on page two,
and "level" control in the next section. Further, the
photograph in the introduction shows the same control with a callout
identification note labeled "Signal Adjust." No wonder
readers get confused! Yet the author of the example knew what
he was trying to write about and, most certainly, he was writing
to himself.
When writing labeling, especially for an over-the-counter (OTC)
device, the author must know the reading level of the target audience.
If data on reading levels is not available, this may necessitate
reader interviews to establish a reading level for the target
audience. If the device is designed for home use, a useful guide
is Write It Right available through DSMA.
Refer to Actual Device
One simple way to reduce control identity confusion as described
above, reduce other types of labeling errors, and increase clarity
is for authors to keep a labeled instrument, kit, or photograph(s)
nearby and refer to it as they write. It is easier to write the
truth when you know the truth. Make sure the terminology and descriptions
in the labeling match that on the actual device. It is best to
always use the same title for each given item or control throughout
the manual, insert, label, and advertisement. Likewise, the same
title should be used in charts, figures, or screen displays such
as cathoderay tubes, LCD panels, etc. Remember to write
to your intended readers, write with a labeled device or photographs
in sight, and use consistent titles.
Obvious Identification of Controls
Because the title of controls or other items in screen displays
and other labeling should be exactly the same as in the labels
on equipment, reagents, accessories, etc., authors may need to
develop and use an appropriate correlation technique for corresponding
titles in instruction manuals, package inserts, etc. One common
and simple technique is to use all capitals for the titles of
controls in labeling. For example:
The associated text, for example, might state:
Flip the POWER SWITCH to ON.
In about three seconds, the READY LAMP will illuminate.
Now press the HEAT button to switch the heater on.
With this correlation technique, the words "on" and
"off" are capitalized in the labeling only when they
actually appear on the instrument control panel. Note that "ON"
is capitalized in "POWER switch to ON" as the actual
switch has "POWER," "ON," and "OFF"
printed by it. In contrast, note that "on" is not capitalized
in the statement "to switch the heater on" as it is
not a label of a control on the device. Also, be careful to use
a simple correlation system that is readily apparent to the intended
audience.
Don't Distract Reader
Readers are very busy trying to learn how to use a new device.
They should not be annoyed by any unnecessary distractions such
as:
For a person trying to read in a hurry, a font such as script
can be a major distraction; therefore, it is best not to use script,
italics, or any other unusual or hardtoread typefaces.
Remember, you have decided to write for the benefit of the intended
audience. Forget about your personal preferences and use only
the most common fonts. Also, select a type size that is readable
at the intended distance. For example, labeling displayed on the
screen of a wallmounted heart monitor should be readable
from several feet away. Also, use a consistent format throughout
the document. Check the format and section titles against information
on the contents page. In some cases, such as for in vitro diagnostic
products, the arrangement of information in the labeling may be
dictated by a regulation. Page numbers should not be referenced
in instruction or service manuals. It is too easy for the actual
page numbers to be changed during the original writing or when
the manual is updated. It is much better to refer to paragraph
titles or numbers as these are less likely to change; and, if
changed, titles are more noticeable by writers and typists than
are page numbers. The use of correct figure numbers is easy
just check them.
Short and to the Point
It is important to use sentence structure that will convey the
intended message with a minimum of misinterpretation or need to
reread. Tests have been conducted to determine the ability of
readers to follow instructions in a sentence based on the number
of activities to be performed. The average person's ability to
follow instructions decreases rapidly when a sentence contains
more than two facts. (Keep in mind your own experiences in reading
instructions.) Therefore, sentences in labeling need to be short
and to the point. Avoid long strings of adjectives and be specific.
Try to be as specific as possible with your instructions. For
example, "ambient" or "room temperature" generally
should not be used. Instead specify the desired or necessary range
of operating conditions. In many cases a list of activities to
be performed is better than burying the facts in long sentences.
A numbered list is better if the user may have to repeat any part
of the procedure. If it takes lots of words to get to the point,
the reader will probably miss the point! Short, choppy sentences
are acceptable in instruction manuals and other labeling. You
are not trying to entertain readers with beautiful, flowing prose
rather, you want to catch their attention with key
facts so they correctly perform the specified instructions. Thus,
use short sentences, get to the point, be specific, and keep graphics
and pictures near the corresponding text.
Gobbledygook
Another way to be more specific and shorten sentences is to avoid
"gobbledygook." The following terms were collected from
actual instruction manuals:
| ORIGINAL | PREFERRED EQUIVALENT |
| Makes provisions for | * |
| Serves to | * |
| At the time of | When |
| In conjunction with | And |
| Carried out in | Perform |
| Comes up to | Reaches |
| Will also serve as a chance to | May |
| Will be sure that will | Ensure |
| Available through the use of | * |
| Care should be used so as not to | Be careful |
| Be provided for positive determination | * |
| Causes power to be applied to | Switches power to |
| Due to the fact that | Because |
| Take the form of | Be |
In most cases, the equivalent term in the list can replace the
original term. For the asterisked items, the equivalent is simply
a direct statement of what is intended. Of the terms listed, the
combination most often used is "makes provision for."
Simply eliminating "makes provision for" and "be
provided for" from labeling will result in an immediate improvement
for readers.
Introduce Each Item
Always introduce each control, indicator, device, or subject before
it is discussed in the text. The introductions should be brief
and may be very brief. Keep in mind the items will be described
in more detail later. Abbreviations and new or uncommon terms
should be defined. The introductions and definitions prevent readers
from going into mental shock, breaking their train of thought,
and asking: What is this? By then readers have probably forgotten
the last two or three facts read. Also, readers may wonder about
any "cliffhanging" item when they resume reading.
This disturbance may detract readers from fully assimilating the
next instructions being read. To avoid distractions and confusion,
a writer of labeling should always:
With respect to definitions, a writer should never give a new
meaning to an existing common term in the language. To avoid this
disservice, coin a special term or code number such as Class Q,
Code 1, or Level 2.
Accentuate Key Terms
Whenever it is stated in instructions that something shall be
done, then "shall" should be set in bold type, or otherwise
delineated. Likewise, caution and warning statements should be
emphasized by boxing, bold type, etc. Underlining should not be
used as it makes the descending part of a letter hard to read
and appears to be top lining on some printers. Refer to any regulations
or standards for a specific product and use the recommended or
required caution statements. When standard terminology exists
in a consensus standard, creating new caution statements is not
advisable. Confusion is less likely to occur when one stays with
the commonly understood terminology.
Select Words Wisely
When large print is needed for reading at a distance or to attract
attention to signs, caution labels, and screen prompts, words
generally should be short in order to fit the available space.
This rule also applies to the wording on control labels. This
situation places a burden on the writer to select terms that convey
the desired message. Consider the following wording from two actual
highway signs:
| PLANT TRAFFIC ENTERING HIGHWAY | NO FISHING
OFF BRIDGE |
Have you ever been run over by a pachysandra? If you can't fish
off the bridge, does that mean you are allowed to fish only on
or from the bridge? Better choices for the intended messages are:
"Traffic entering highway" and "No fishing from
bridge".
Test Labeling
Finally, always have someone not familiar with the product operate
it exactly according to the draft instructions, labels, screen
displays, etc. You should not do any coaching because coaching
destroys the validity of the trial. By coaching you transfer your
"memory" to the user. Therefore, no coaching
this is the "acid" test good luck! During
the trials, note any significant problems and make appropriate
corrections to the instructions, prompts, or other labeling.
Label Integrity
All labels shall be designed and applied to devices and containers
so that the labels will remain in place and legible during the
customary conditions of distribution, storage, and use [820.120(a)].
Likewise, other labeling such as user instructions should remain
legible during customary storage and use. For example, labeling
printed by machines onto plastic in vitro diagnostic media plates
is often smeared and thus is inadequate [FD&C 502(f)]. The
manufacturers of such devices should assure that the print is
legible and will remain legible until used.
Many magazines use "wet" ink which smears when touched
by sweaty or oily fingers. Obviously, this type of ink will not
meet the design requirements for package inserts, instruction
manuals, and the like.
Labels may be mounted by adhesives, screws, rivets, drive screws,
etc., or printed or etched onto panels and/or onto controls. The
labels should be located so that they will be seen but not be
abraded during use. (Many of us have seen the unbelievable cases
where safety labels on ladders and riding lawnmowers were placed
in the foot rest areas. Of course, they were worn off after a
few uses!)
Approval Policy and Procedure
The review of labeling from the design stage through to the finished
device should be documented like the review of other significant
components. This includes the labeling development, any changes,
and final approval. Documentation should be included in the design
history file of the procedures used, signature of the responsible
person, and date. Because several activities are performed and
controlled during the development and use of labeling, Table 11.1,
"Drafting and Approval of Labeling" and "Final
Approval of Labeling, Advertising, Etc." are presented as
guidances. This table contains a typical sequence of events required
to develop and control labeling. Other controls are discussed
below.
Before release for use, labeling should be reviewed and approved
by product development, service, marketing, quality assurance,
and other appropriate managers (820.30). Manufacturers need to
have a policy/procedure which covers the drafting, review, and
approval of labeling. Approval forms are generally used in conjunction
with such a policy/procedure. A sample approval form and procedure
are presented at the end of this chapter. Other procedures and
forms such as "Change Control" are referenced in this
procedure. Note that this procedure also covers other elements
such as a correct device master record, correct transfer of labels
into production, lot control, change control, etc. Samples of
various procedures appear at the end of chapters throughout this
manual.
Design Transfer
Specifications are required in the device master record for the content and physical design parameters
of labels. (see Chapter 8). Labeling specifications include the
engineering drawing and/or artwork for each label, appropriate
inspection or control procedures, and appropriate procedures for
attaching the labels. All procedures, drawings and artwork should
have the name of the preparer, an approval signature, and a date.
The approval signature, date, etc., may be on the back side of
artwork or on a label approval form. Further, artwork may contain
only an identification code or title if the "content"
of the artwork is duplicated on approved engineering drawings,
adequately identified, or crossreferenced with respect to
the label approval form. That is, a manufacturer should be able
to identify isolated artwork.
Hardcopy labels, package inserts, and similar labeling are also
specified and purchased as components (see Chapter 8). For correct
purchase and use of labeling, specifications are usually stated
on engineering drawings and/or purchase specifications. Thus,
artwork or "copy" alone will not fulfill the device
master record and purchasing control requirements for labeling
except for the most simplistic labeling such as brief errata sheets.
The engineering drawings or purchase specifications should specify, as appropriate, the label substrate, dimensions, ink, finish, mounting method, etc., so that the purchased label will remain attached and legible during the customary conditions of processing, storage, handling, distribution, and use.
| Table 11.1 TYPICAL SEQUENCE OF THE CONTROL OF LABELS | ||
| PHASE | SECTION | CONTROL ACTIVITY |
| 1. Design | 820.30, 820.120 & 820.130 | Meets needs of user and intended use.
Text review. Quality of mounting such as rivets, adhesives, etc. Quality of ink, anodize, etc. Content per 21 CFR 801 and 809 company claims and standards. |
| 2. Verification/Validation | 820.120, 820.75 & 820.30 | Simulated or actual processing such as sterilization, shipping tests, label affixing, etc. Saline, alcohol, and coffee spill tests? |
| 3. Changes | 820.30 & 820.75 | Establish and maintain approval procedures. |
| 4. Documentation | 820.30,
820.181 & 820.120(e) | Approve, date and change control label drawings. A key label shall contain the control number of the finished device either on or accompanying device. |
| 5. Procurement | 820.120(b) 820.180 | Proofread before release to inventory stock. Record signature of proofreader and date. |
| 6. Storage | 820.120(c) & (d) | Store labels to prevent mix-ups.
Restrict access to authorized persons. |
| 7. Separate operations | 820.120(d) | Separate multiple operations to prevent mix-ups. |
| 8. Area inspection | 820.120(d) | Before beginning labeling operations, designee to inspect area and remove extraneous devices and labels. |
| 9. Issuance | 820.120(b), 820.120(e) &
820.65 | Examine for identity and, where appropriate, expiration date and control number. Record date and person examining labels. |
| 10. File Sample | 820.184(e) | Copy of primary identification label shall be in the device history record. |
| 11. Inspection | 820.80(d), 820.86
& 820.80(e) | Inspect finished device per written procedure. Designee shall check all acceptance records and test results and see that requirements are met and records are present and complete. |
Front panels, other instrument panels, meters, fuses, pushbuttons,
and the like often are either labels or contain labels and thus
should, as appropriate, meet device master record and control
requirements. Component specifications, assembly drawings, and
test/inspection procedures are appropriate controls to prevent
mixup of meters, push buttons, and other labeled instrument controls.
Whether a manufacturer considers a software driven display to
be labeling or data makes little difference under the QS regulation
because, either way, the finished device labeling or data should
meet the device master record specifications. When manufacturers
develop and validate software, they should also review any electronic
displays to see that the "labeling" meets all applicable
requirements, such as adherence to specifications in the device
master record, correct parameter identification, agreement with
the instruction manual, and, of course, correct display of performance
data.
Production Controls
When reviewing or auditing labeling operations, it is wise to
keep in mind that the GMP requirements are flexible. The degree
of labeling control needed to satisfy the QS regulation varies
considerably for different devices and operations. In order to
avoid wasting money and increasing the cost of health care, manufacturers
need to give considerable and prudent thought to the appropriate
level of control needed for their operations as allowed by 820.5.
Information and guidances presented in this manual should aid
manufacturers in making these decisions. The level of control
needed should be reconsidered when products are changed. Likewise,
the controls needed, and the success of the existing control program,
should be reviewed during quality system audits (see Chapter 17).
Medical device manufacturers should incorporate in their quality
system several elements that relate to labeling in order to meet
the GMP requirements. The quality system should be adequate to
assure that labeling reflects user needs, meets the device master
record requirements with respect to legibility, adhesion, etc.,
and assure that labeling operations are controlled so that the
correct labeling is always issued and used.
Receipt and Inspection
Upon receipt, all packaging and labeling materials, including
preprinted containers, inserts, and preprinted packaging materials,
should be examined and, if deemed necessary by the company, tested
to assure conformance with specifications as discussed in Chapter
10, Purchasing and Acceptance Activities. Also, samples of labels,
including labeled panels, meters, etc., shall be proofread by
a designated individual(s). After being accepted by a responsible
individual, these components may be placed into inventory or into
production. These inspections shall be recorded in the device
history record as required by 820.80(e) and 820.120(b) to show
that inspection and proofreading were performed. The inspection
record for device labeling should be kept simple.
Area Separation and Inspection
All labeling and packaging operations should be separated to the
degree necessary [820.120(d)] to assure there are no mixups between
similar products or labels. Separation may be either a physical
or spatial separation or by performing the labeling and packaging
at different times for different devices. Separation is not required
when mixups are impossible, such as the case of labeled front
panels that only fit the intended family of devices.
The likelihood of a labeling mixup determines how stringent production
area controls should be. For example, label control need not be
stringent if only one product or dissimilar products and labeling
that are unlikely to create confusion are processed. Before beginning
any packaging and labeling operation in which mixups could occur,
the production area and equipment for the operation should be
thoroughly examined to ensure that any devices and labeling materials
remaining from previous operations have been removed. It is important
to make certain that the surrounding area, tables, packaging lines,
printing machines, and other equipment are cleared of labels and
other materials used in the previous operation.
Unused labeling that contains precoded serial numbers, manufacturing
dates, expiration dates, control numbers, etc., should be destroyed
and not returned to the label storage area. The GMP requirements
do not include reconciliation of the number of labels used with
the number issued, although, this control is recommended for some
devices, such as when different sizes of the same product are
being packaged or otherwise labeled.
Where feasible, labels for similar devices should be designed
with different shapes and colors to reduce the probability of
mixups. Thereafter, all printed packaging and labeling materials,
including preprinted containers, inserts, and preprinted packaging
materials shall be stored in an area and manner suitable to prevent
mixups [820.120(c)]. For example, if labels from one container
are accidentally dropped, they should be stored so they will not
fall into another container of similar labels. Labeling should
be identified and segregated to the degree necessary to prevent
mixing of similar labeling. Access to labeling should be limited
to authorized personnel.
Storage control should be appropriate for the number and kind
of devices. For example a manufacturer that has only one product
with one label does not need an elaborately controlled storage
area. Similarly, a manufacturer with only a few types of devices
having dissimilar labeling would not normally require stringent
control.
One case that requires dedicated attention to storage and control
is prelabeled "sterile" but notyetsterilized
devices. Manufacturers should make absolutely certain that mixups
cannot occur. Also, they should make certain that all samples
used for market promotion are sterile or labeled with a manifest
caution statement, because a packaged and labeled marketpromotion
sample might be used by the recipient. One approach is to sell
sterile samples at zero cost so that such samples are subjected
to all of the company product release and distribution controls.
Quality awareness training is required by section 820.25. Marketing
personnel should be informed of labeling control requirements
and the consequences of a violation.
Label Check and Record
In summary labeling should be carefully examined to assure that
the contents of the labeling comply with the labeling specifications
in the device master record. This examination should include any
control numbers or expiration dates used on the labels. A record
of this check, including the date and name of the person performing
the examination, should be made in the device history record.
If expiration dates are used, they should reflect the time limitations
within which the device is fit for its intended use when stored
and used per its labeling. The manufacturer should have stability
test data establishing how long the device will remain fit for
use to support expiration dates.
If label mixups cannot occur for example, a manufacturer
makes only one device or uses only one label and
there are no control numbers or expiration dates, the original
inspection when the labeling was placed into inventory is an adequate
check for compliance with the device master record specifications.
A second check need not be performed because it serves no purpose
(820.5). If, however, there is any possibility that incorrect
labeling can be used, a second check should be made when the labeling
is issued for application, packaging, or shipping.
Control Numbers
Devices intended for surgical implant, and devices intended to
support or sustain life and whose failure to perform properly
can be expected to result in significant injury, shall contain
a control number, serial number, letters, etc., for traceability
(820.65). Procedures for establishing and maintaining control
numbers shall be documented in the DHR. This means a control number
for the finished device, and not the label itself. Although this
control number may be on a label, most labeling also contains
another number, such as a drawing number, for control of labeling
configuration and procurement.
The control number for traceability need not be on every label
on the device; however, the control number should appear on the
primary label that goes to the ultimate user. The label on a shipping
carton does not meet this requirement because bulk items may go
to a central distribution point in the userfacility and
the shipping carton will most likely be disregarded.
Access Restriction
Access to labeling should be restricted to authorized personnel.
Labeling also should be stored in an adequately segregated area
to minimize the chance of mixups. Segregation is recommended because
it increases the control over the label storage area with no significant
increase in cost.
Labeling is a component of the device and part of the device design
output; therefore, all changes to labeling should be made under
a formal change control system. Design changes shall meet 820.30(i);
and other changes are made according to 820.40. Any changes to
labeling should be formally reviewed and authorized before implementation.
That is, follow the guidance in this chapter as if new labeling
is under development.
When making changes to primary aspects of a device and to primary
documentation, the review group should determine if any secondary
items such as labels or instructions are affected and also need
changing. There should be a checkoff block on changeorder
forms, or any other change control mechanism, for recording that
the effect of the primary change on labeling was considered and
appropriate action was taken. The failure of a change control
system to alert employees of basic requirements is considered
to be a serious deficiency in a quality system.
Devices that are prelabeled "sterile," but are not yet
sterilized, require be controlled at the manufacturer and during
shipment for further processing. Likewise, devices that have been
sterilized and shipped to the manufacturer's warehouse or other
controlled distribution point before final release should be properly
labeled. The pallets, or designated unit, should be marked to
indicate the status of the device, such as "nonsterile,"
"sterilized: awaiting test results," or an equivalent
statement (820.86). The company should be able to show that it
has control of the devices until final release and, could have
them destroyed or returned for reprocessing if necessary. Unless
so qualified, a distributor's warehouse or facility is
not considered a controlled distribution point.
The QS regulation states that each manufacturer shall establish
and maintain procedures to ensure that mixups, damage, deterioration,
contamination, or other adverse effects to product do not occur
during handling (820.140).
The storage regulation at 820.150 states, "(a) Each manufacturer
shall establish and maintain procedures for the control of storage
areas and stock rooms for product to prevent mixups, damage, deterioration,
contamination, or other adverse effects pending use or distribution
and to ensure that no obsolete, rejected, or deteriorated product
is used or distributed. When the quality of product deteriorates
over time, it shall be stored in a manner to facilitate proper
stock rotation, and its condition shall be assessed as appropriate.
(b) Each manufacturer shall establish and maintain procedures
that describe the methods for authorizing receipt from and dispatch
to storage areas and stock rooms."
Manufacturers of sterile devices commonly label devices as sterile
at one establishment and ship them to another facility or a contract
sterilizer for sterilization. Shipments of nonsterile devices
labeled as sterile are clearly misbranded and adulterated, and
if diverted into consumer channels, could create a potential health
hazard. FDA recognizes that this longstanding practice is an economic
necessity for many manufacturers. Therefore, to meet the needs
of these manufacturers in a way that will also assure the protection
of the public health, FDA added Part 801.150(e) to the Code of
Federal Regulations (CFR). It is reprinted below.
(e) As it is a common industry practice to manufacture and/or
assemble, package, and fully label a device as sterile at one
establishment and then ship such device in interstate commerce
to another establishment or to a contract sterilizer for sterilization,
the Food and Drug Administration will initiate no regulatory action
against the device as misbranded or adulterated when the nonsterile
device is labeled sterile, provided all the following conditions
are met:
(1) There is in effect a written agreement which:
(i) Contains the names and post office addresses of the firms
involved and is signed by the person authorizing such shipment
and the operator or person in charge of the establishment receiving
the devices for sterilization,
(ii) Provides instructions for maintaining proper records or otherwise
accounting for the number of units in each shipment to insure
that the number of units shipped is the same as the number received
and sterilized,
(iii) Acknowledges that the device is nonsterile and is being
shipped for further processing, and
(iv) States in detail the sterilization process, the gaseous mixture
or other media, the equipment, and the testing method or quality
controls to be used by the contract sterilizer to assure that
the device will be brought into full compliance with the Federal
Food, Drug and Cosmetic Act.
(2) Each pallet, carton, or other designated unit is conspicuously
marked to show its nonsterile nature when it is introduced into
and is moving in interstate commerce, and while it is being held
prior to sterilization. Following sterilization, and until such
time as it is established that the device is sterile and can be
released from quarantine, each pallet, carton, or other designated
unit is conspicuously marked to show that it has not been released
from quarantine, e.g., "sterilized -- awaiting test results"
or an equivalent designation.
Overlabeling by placing a new label over an old label is
discouraged by FDA but is acceptable as long as the new label
and its use meet GMP requirements [(820.30, 820.120, 820.90(b)(2)]
for user needs, attachment, legibility, reprocessing, and change
control. Overlabeling is also discouraged in some foreign
countries.
Exhibits that cover labeling design and labeling control are presented
on the following pages. These exhibits show how some GMP requirements
for label control may be met. These procedures and forms may need
to be modified to meet the needs of a specific operation.
Drafting and Approval of Labeling
This drafting and approval procedure is used to establish a uniform
system for controlling the content of labeling and for approving
labeling. This procedure is adaptable for use by any size manufacturer.
The approval form which follows may be used with this procedure.
Approval Form for Labeling, Advertising, Literature, etc.
This form is intended for use by a medium to large manufacturer,
however, the checklist style can be adapted even to a small manufacturer.
The areas of concern are listed under the group that is responsible
for that concern. Thus, every department has input into the acceptability
of the labeling.
Administration Set Label
This example of a label for an administration set begins with
a complete description of the device inside the package. The directions
for use section is arranged so that each point in the directions
for use is numbered and only one point is made for each step.
The various points in the directions are short and to the point.
Where emphasis is needed, as in the case of air bubbles, the information
is bolded for further emphasis.
Labeling Control Record
This blank copy of a labeling control record shows what a sample
form looks like. At the bottom of the form, there is space to
attach the actual labeling used so that a comparison of the actual
labeling used versus that required can be made during product
release review.
Device History Record: OB/GYN (Plate)
The history record exhibited here is limited to the filling operation
for a media product. The form has space to print the same label
as printed on the plates during the filling operation for label
control and release review. This technique eliminates human copying
errors.
User/Reader Comments
Feedback is an important element in any QA system. Whenever manuals
or instructions form part of the labeling for a product, it is
wise to solicit review from persons not familiar with the use
of the product. These people can be employees of the manufacturer
or, as in this exhibit, actual users of the product. The information
received will reflect the problems encountered by persons trying
to follow the instructions without any preconceived knowledge
of the actual operation of the product.
PAGE 1 OF 3
Procedure Policy Title: DRAFTING AND APPROVAL OF LABELING SOP#:_______
Prepared by:________________________________ App: ___________ Date: __________________
Prep. Date: ____________ Rev:_______________________ Date:___________________
ECN History: _______________________________________________________________________
___________________________________________________________________________________
1.0 PURPOSE
To establish a uniform procedure for controlling the content of
labels and labeling and obtaining approval within our company.
To assure compliance with GMP requirements and with company policy
directives.
2.0 SCOPE
Applies to all devices including those used for market research
or clinical investigations.
Advertising material is excluded from this SOP. It is covered
by our SOP #____, "Advertising Material Control and Approval."
3.0 REFERENCE DOCUMENTS
3.1 Food and Drug Administration LABELING, GMP, etc. requirements in 21 CFR Parts 800-1299.
3.2 SOP #_____, Advertising Material Control and Approval
3.3 SOP #_____, Change Control System
4.0 FORMS
4.1 Form SOP #_____, Labeling Development and Verification Checklist
4.2 Form SOP #_____, Labeling Approval Form
4.3 Form SOP #_____, Engineering Change Order Form
5.0 DEFINITIONS
5.1 Labeling is all labels and other written, printed or graphic
matter accompanying or attached to the device or its container.
6.0 PROCEDURE
6.1 Preparation and Approval
PAGE 2 OF 3
The Labeling Development and Verification Checklist should be
used as a guidance for all activities because the finished labeling
must be evaluated versus this checklist.
6.1.1 The need for a label or labeling is determined by an operating
department such as Engineering, Marketing, Manufacturing, or Quality
Assurance. Marketing, as appropriate, will conduct and document
literature searches and perform design input market research to
determine any special needs of the users. Design input, regulatory,
safety, and other appropriate information shall be used to create
a labeling specification.
6.1.2 The Engineering Department prepares a manuscript complete
with illustrations or prepares a drawing(s) of the label showing
the wording, label use, and/or location. The label may be on a
front panel drawing or other engineering drawing.
6.1.3 When final prototypes and/or pilot production models are
available, the labeling shall be verified and the results recorded
on the Labeling Development and Verification checklist. If needed,
appropriate corrective action shall be taken by the appropriate
department. The completed checklist shall be filed with the device
design verification records.
6.1.4 Before final approval, labeling will be discussed at appropriate
design review meetings. The minimum attendees are the originator,
Engineering, and QA.
6.1.5 The Engineering Services Department then prepares form SOP
#_____, Labeling Approval Form, and circulates it to the originating
department, Training and Education, Marketing, and Quality Assurance
for approval. (See the following sample approval form.)
6.1.6 Engineering Services will coordinate and file all labeling
verification checklists, notes, approvals and approval forms in
the design history file.
6.1.7 When approval is received from all parties, the label or
manuscript is assigned a drawing number and is released and added
to the product structure (DMR Index) following the Change Control
System (SOP #_____) procedure.
6.2 Implementation and Control
6.2.1 When labels or labeling are produced, Quality Control must
proofread the material and verify that it is correct by first
article inspection and so indicate by signing an appropriate document.
6.2.2 All labels and labeling will be reviewed by QA for lot control
requirements. Each original document will be marked by Engineering
Services to indicate the level of control required. At least one
label on each device intended for surgical implant into the body
or to support or sustain life must have a lot, serial, or other
control number. See 820.65, Traceability.
PAGE 3 OF 3
7.0 EXPERIMENTAL DEVICES
7.1 Labels and labeling for experimental or investigational devices
are required.
7.2 The documentation need not be as complete as for production
labels and labeling; but, it must be adequate to allow
procurement of the labels or labeling and adequate for the intended
use. If appropriate, such labeling must meet 21 CFR 812.5.
8.0 CHANGES
8.1 Any changes to released labels or labeling are accomplished
according to SOP #_____, "Change Control System".
9.0 SCHEDULES
(Design QA requirements are presented below. There are also related
production requirements.)
9.1 Drafts must be generated according to a schedule that
allows a normal approval procedure. While urgent copy approval
is occasionally necessary, it should not become standard operating
procedure.
9.2 All labels must be approved according to the routine
engineering schedule for components.
9.3 Labeling must be approved before or when the device
is released for full-scale production. HOWEVER, any pilot units
placed in commercial distribution must be labeled with approved
pilot or final labeling.
9.4 The design review for any pilot lots and the design review
of initial full-scale production lots shall include a design
review of labeling.
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Updated 1/1/1997
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