Quality System Regulation Requirements for Labeling

In order to meet the Good Manufacturing Practice requirements of the Quality System regulation, medical device manufacturers must incorporate several elements related to labeling into their quality assurance program. The Quality Assurance Program must be able to guarantee that the labels on products meet Good Manufacturing Practice demands with legibility and adhesion. This will ensure that labeling operations are under control at all times and only correct labeling of cosmetics and drugs is used.

Labeling covers everything from equipment and control labels to package labels, directions for use, and maintenance manuals. Displays on CRTs and other electronic message boards that include instructions, prompts, cautions, or identification parameters are considered labels.

According to 21 CFR 820.30, the design history file (DHF) must list specific content and physical design parameters for labels. The requirements for each label are: an engineering drawing and/or artwork, appropriate inspection or control procedures, and attaching the labels. Artwork, drawings and all other associated documents must include the name of the artist, approval signature and date. The approval signature, date, and other information may be on the back side of artwork or on a label approval form. In addition, if the art contains an identification code or title that is present on drawings that are approved by engineering or it is cross-referenced with respect to the label approval form, then this will be acceptable.

Hard copy labels, package inserts, and similar labeling must be specified and purchased in advance. The correct way to purchase and use labels is by specifying it on engineering drawings and/or purchase specifications. In other words, simply having artwork or "copy" for labeling will not be enough to meet the device master record requirements, except in very rare circumstances such as when you have short errata sheets.

The engineering drawings or purchase specifications must include the label's substrate, dimensions, ink color and finish, mounting method etc., to ensure that the purchased label will remain firmly attached and legible under common conditions of processing, storage, handling distribution and use.

Front panels, instrument panels, meters, fuses, pushbuttons--all of which might have labels on them--must meet device master record and control requirements. To prevent mixups of meters, pushbuttons, and other labeled instrument controls, consider using component specifications, assembly drawings, or test/inspection procedures. There is generally no need for extra controls on front and other instrument panels to avoid mix-ups.

Requirements for Labeling of Cosmetics and Drugs

Being flexible with labeling requirements allows for a better quality assurance program. The required level of labeling control to comply with Quality System regulation differs based on the device and operation. To save money and prevent the rise of healthcare costs, manufacturers must think critically about how much control they need in their operations. This blog will present information and guidelines to assist manufacturers in making informed choices. The level of control should be reconsidered whenever products are added or changed. The controls needed for the success of the existing control program must be reviewed and analyzed during QA system audits.

Cosmetic Labeling

The United States federal government, through the FDA and FD&C Act, demands that all cosmetics within our borders adhere to stringent labeling requirements published by the FP&L Act. Labeling encompasses any written, printed, or graphic material that appears on the product itself or its accompanying packaging. The FDA mandates that label statements are displayed on both the inside and outside of any container or wrapper enclosing the product. As per the FP&L Act, it is mandatory to include ingredient labeling and a statement of net quantity on the principal display panel only when labelling an outer container. If cosmetic products fail to display the necessary information as outlined in 21 CFR 701 and 740, then they are considered misbranded and can face significant repercussions. It is absolutely essential to follow the labeling requirements for cosmetics precisely in order to guard your products from any legal repercussions.

The primary display panel of the label-- which is prominently viewed when a product is normally on sale (21 CFR 701.10)-- must include an accurate statement of the product's name, details describing its purpose or nature, and net contents expressed in terms such as weight, measure or numeric count. For optimal visibility, the declaration must be placed at the bottom of the container in a line that is close to its base. Additionally, all text should be sized according to regulatory guidelines depending on how large or small your packaging may be. According to the Food and Drug Administration, cosmetics that are solid, semi-solid or viscous must include a net quantity of contents measured in pounds and ounces. To ensure accuracy, all liquid measurements must be expressed in US gallons with corresponding quart, pint and fluid ounce labels included on the product packaging. Whenever the content amount is one pound or higher, and when it's a pint or greater, it must be expressed in ounces with an additional statement of the largest whole units (for example: pounds/ounces or quarts/pints/ounces) inside parentheses. You can also describe the net quantity of contents in terms of metric weights and measures.

As per the Federal Code of Regulation (21 CFR 701.12), it is mandatory for companies to make known their name and place of business on an information panel placed on the label associated with all products they market. To ensure that the package arrives at its intended destination, it is important to include all pertinent information such as street address, city, state and zip code. However, if a shop or company can be found in any current directory (such as City Directory or Telephone Book), then providing the street address isn't necessary. It is essential to note that when a distributor differs from the manufacturer or packer, this must be stated on the product's label with an appropriate phrase like "Manufactured for ......" or "Distributed by......."

Label Integrity

All labels must be designed and applied to devices and containers so that the labels will remain in their original place and be legible under typical conditions of distribution, storage, and use. Also, other labels, like user instructions, should be still readable during regular storage and use. For example, if machines print labels onto plastic in vitro diagnostic media plates, the label sometimes smears and becomes unreadable [FD&C 502(f)]. The manufacturers of such devices must ensure that the print is legible and will remain so until use.

Receipt and inspection

Once you receive the materials, unpack and examine them to make sure they match the specifications detailed in your order. This includes containers, inserts, and other packaging materials that may already have been printed. Every label sample must be gone over by one or more appointed people. Once a responsible individual accepts them, these components can go into either inventory or production. According to 21 CFR 820.80(e) and 21 CFR820.120, these activities done to check for acceptability must be written down in the device history record as evidence that inspection and proofreading occurred. Keep your device labeling acceptance record clean and simple.

Dividing and Inspecting

To avoid any confusion between similar products or labels, all labeling and packaging operations should be as separate from each other as possible. Separation can be achieved physically or spatially, or by performing the labeling and packaging at different times for different devices. When mixups are impossible, such as when labels match the family of panels or intended instruments (devices), separation is not required.

Strictness of production area controls should be based on the likelihood of a labeling mix-up. for example, less label control is needed if only dissimilar products are being processed. Before beginning any operation in which product mixup could occur, examine the production area and equipment thoroughly to ensure that devices and labeling materials from previous operations have been removed. It is important to clear the surrounding area of labels and other materials used in the previous operation, including tables, packaging lines, and printing machines.

All labels with pre-coded serial numbers, manufacturing date, expiration date, control number etc. that are not being used should be destroyed and not put back in the label storage area. Although the Quality System regulation does not require it, for some devices it is recommended to reconcile the number of labels used with the number issued--such as when different sizes of the same product are being packaged or labeled.

Storage

As required by 21 CFR 820.120, all mixups must be prevented when storing printed packaging and labeling materials, including preprinted containers and inserts. Labeling should be sorted and set apart to avoid mixing similar labeling. Only those with authorization should have access to the labeling.

The level of storage control your company needs is relative to the number and type of devices you have. For example, a business that manufactures one product with one label does not need a very controlled storage space. A company with only a few types of devices and dissimilar labeling would not usually require stringent control.

One case that deserves storage and control is pre-labeled "sterile" but "not-yet- sterilized" devices. To avoid mixups, firms should take care to ensure that all samples are properly labeled and sterile. If any samples will be used for marketing purposes, they must be clearly marked as such, and caution should be exercised to prevent them from being mistaken for actual products.

Label Check and Record

The moment a label is made for a device, it is critical to check that the contents of the label actually match what similar devices require. This verification step must be carried out on every different label interpretation against corresponding entries in the master records. Please examine the labels for any control numbers or expiration dates. The device history record shall include the date and name of the individual who carried out this inspection, as well as a copy of the completed check.

If expiration dates are used, they must show how long the device can be stored and still work properly for its intended use, if used according to labeling. To ensure that the device will work properly for an extended period of time, manufacturers should have stability test data.

If a company only makes 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.

Changes

According to the device master record, labeling is part of it; thus, any changes made to the label must be done under a formal change control system that is similar (if not identical) to the one required for specifications. No changes to labels can happen without a formal review and authorization from the proper channels.

While assessing changes to a device or its documentation, the review group must discern if any subsidiary components, like labels or instructions, are also impacted and need alteration. A check-off block for whether the primary change's effect on labeling was considered and appropriate action was taken should be included on change-order forms.

Relabeling and Over-labeling

Although over-labeling by placing a new label over an old one is discouraged by the FDA, it is acceptable as long as the new label and its use meet GMP requirements for attachment, legibility, reprocessing, and change control. (This practice is also looked down upon in some foreign countries.)

Control Number

Devices that are meant to be surgically implanted into the human body or devices that support or sustain life need a control number on each unit, lot, and batch of finished devices for traceability in order to avoid significant injury [21 CFR 820.65]. The finished device requires a control number, which is different from the label number. Usually, labeling has another number for configuration and procurement purposes, such as a drawing number.

Although the control number for traceability does not need to be on every label of the device, it must appear on the unit label that is given to the person who will use it. This shipping carton for bulk items does not meet the requirements because usually, central distribution points in user-facilities receive these kinds of items, and the shipping carton would likely get discarded. The control number must be on the label so that the nurse or other user can see it easily.

Sterile Device Labeling

Devices that need to be sterile over their entirety should have special attention given when being labeled . If a device only needs sterility in certain areas (For example: the lumen of certain devices,) then the label should inform users of what is actually intended to be "sterile" inside of the package. A possible statement limiting this might be:

"Do not use outside of aseptic areas without proper precautions, as only the fluid path of the set is sterile and nonpyrogenic."

Devices that require sterilization before use. In this case, the label should have enough information about at least one appropriate way to sterilize it and any safety measures to take. For instance, the label might mention:

• requires special cleaning methods.
• any changes to the physical device that may result from reprocessing, which could affect how safe, effective, or usable it is.
• the number of times a device can be cleaned and reused without compromising safety or function.

Some manufacturers label their single-use sterile devices with a warning against resterilization and reuse. Other devices cannot be recleaned because they are not durable enough to go through the process again or were not designed to support it. In areas where it is common practice to reuse materials, manufacturers are encouraged to provide the information described in the above list.

Multi-device kits or packages that contain both sterile and nonsterile products can not have a label stating or implying that all contents are sterile. We need to evaluate whether users need instructions on how to open a sterile device package so that the device doesn't become contaminated. If necessary, we should include these type of instructions in the product labeling.

A manufacturer must always review the device's labeling to ensure it reflects current revisions and specifications whenever a modification is made. Some manufacturers notate current labeling by adding a revision code or date to the identification drawing number. The revision date must be included on the package insert or other labeling for in vitro diagnostic products [21 CFR 809.10(b)(15)].

For most medical devices, FDA approval doesn't require shelf-life dating for packaging integrity and sterility. Expiration dating may be necessary when a particular device component, such as a battery or reagent, has limited usefulness. The FDA states that all in vitro diagnostic devices must have an expiration date or some other way to guarantee quality at the time of use. This requirement applies to all in vitro diagnostic devices, both sterile and nonsterile.

Many manufacturers of complex devices and sterile devices use lot or serial numbers for production control, failure investigations, repairs, modifications, or recalls--even though it's not always required by regulation. Lot, batch, or other control numbers are necessary for:

• The certain devices mentioned in 21 CFR 820.65
• Some products may be subject to radiological health standards
• in vitro diagnostic devices [21 CFR 809.10(a)(9)].

In order to adequately label a medical device, the labels and labeling must be designed and procured properly. Not only does effective design need to meet the requirements of the QS regulation, but it also needs to fulfill the customer's wants. There are a few key things to remember if you want to achieve these writing goals, such as: making sure your readers will understand what you're saying, using the right terms for specific devices or controls, and being clear in your labeling.

Contract Sterilization

Devices that are sterilized by a third-party contractor after being manufactured present a unique labeling challenge. A common industry practice is to send the device in its final packaging to the contractor for sterilization. The packaged product is labeled as sterile, even though the goods are unsterile when shipped from the manufacturer to the contractor. In this instance, specific restrictions apply and there must be a written agreement between both parties in effect [21 CFR 801.150(e)].

The 21 CFR 801.150 details the requirements for labeling in transit sterile goods that are being sent to a contract sterilizer, which falls under Other Labeling Exemptions. We must be careful in this situation to make sure that an unsterilized product is not mistaken for a sterilized one. "Visual indicator" labeling can be extremely beneficial for firms, as it allows them to easily see which products have been sterilized and which have not. For example, using indicators that turn color when exposed to steam or ethylene oxide, or stick-on dots that change color after radiation exposure. Keep in mind that while visual clues will let you know the product has been exposed to a sterilant, it cannot guarantee that the item is sterile.

A company should also think about obtaining dosimeters. Dosimeters are devices that change physically or chemically when exposed to a sterilant, usually in an irreversible way. Many contract sterilizers put labels on their clients' products which include a sterilization number that is printed onto the device container or outer shipping containers.

If you want to be sure that your devices have undergone sterilization, audit the facility in-person if possible. This way, you can confirm that sterilization lot numbers are applied after the device has gone through the process.

The regulations on device distribution are contained in 21 CFR 801, Subparts A and E; and Quality Systems Regulation 21 CFR 820.160. Devices that have been sterilized, held or shipped to the manufacturer's warehouse or other controlled distribution point before final release must be labeled correctly.

The pallets should be labeled to show the status of the device, like "Sterilized: Needs Test Results," or a similar sentence. The company must be able to show that it can control the devices until they are finally released and, if necessary, could have them destroyed or returned for reprocessing. Therefore, a distributor's warehouse or facility is not classified as a controlled distribution point. Learn about our FDA consulting services.