World of Confusion
Challenges abound when distributing medical devices globally
by Les Schnoll
U.S. manufacturers of medical devices must comply not only with U.S. Food and Drug Administration (FDA) labeling requirements, but they also face the challenge of labeling in multiple languages if they want to sell their products in the global marketplace.
Section 201(k) of the Federal Food, Drug and Cosmetic Act (FFDCA) defines a label as any "display of written, printed or graphic matter upon the immediate container of any article," and labeling as "all labels and other written, printed or graphic matter upon any article or any of its containers or wrappers, or accompanying such article" at any time while a medical device is held for sale after shipment or delivery for shipment in interstate commerce.1
So far, this is not too difficult to decipher: If it’s on the device, it’s a label; everything else is labeling.
For medical devices distributed in the United States, clarification of the definitions and more specific requirements are identified in the FDA’s 21 CFR 801 and include:
- Name and place of business. The label of a device must contain the name and place of business of the manufacturer, packer or distributor, including the street address, city, state and ZIP code. The firm’s street address can be omitted if it is in the local telephone directory. If the firm listed on the label is not the manufacturer, the firm information must be qualified by an appropriate statement, such as "manufactured for" or "distributed by."
- Intended use. If a packer, distributor or seller intends a device for uses other than those intended by the person from whom it received the device, these parties must furnish adequate labeling in accordance with the new intended use. If a manufacturer knows or has information indicating the device is to be used for conditions or purposes other than what it intended, the manufacturer is required to provide adequate labeling in accordance with such other uses.
- Adequate directions. "Adequate directions for use" means directions that enable the layman to use a device safely and for the purposes intended. These include statements of all purposes for which and conditions under which the device can be used, the quantity of dose for each use and usual quantities for persons of different ages and physical conditions, frequency of administration, duration of application, time of administration in relation to other factors, the route or method of application, any preparation necessary for use and information on exemptions from adequate directions-for-use requirements.
- False or misleading statements. A device is misbranded if it makes a false or misleading statement with respect to another device or includes claims that cannot be substantiated.
- Prominence of statements. A word, statement or other required information may lack the required prominence and conspicuousness: if it fails to appear on the part or panel that is displayed under customary conditions of purchase; if the package contains sufficient space, and the required information fails to appear on two or more panels, each of which is designed to render it to be displayed under customary conditions of purchase; if required labeling fails to extend over package space provided; if there isn’t sufficient label space for required labeling due to placement of nonrequired labeling on the package; or if smallness or style of type, in sufficient contrast between labeling and package background or designs that obscure or overcrowd labeling render it unreadable.
- Exemptions. Exemptions may be granted when device
labeling lacks sufficient space for required labeling, provided that existing
label space is not taken up by including nonrequired information or by giving
prominence to a portion of the required labeling, and existing label space is
not used for any representations in a foreign language. All labeling must be in
English with the exception of products distributed solely within Puerto Rico or
a U.S. territory where the predominant language is not English. In these
instances, the predominant language may be substituted for English. If any
representation on the device label or labeling appears in a foreign language,
then all required labeling must also appear in that foreign language.
Speak their language(s)
If a medical device manufacturer wants to distribute its products globally, it must overcome other sets of labeling hurdles. One of the main challenges today is multilanguage labeling.
Before the enactment of the European Union Medical Device Directives (MDD), there were no requirements to include multiple languages on medical device labels. The impetus to offer more than one language was driven by individual countries and customers. Manufacturers would compete for market share in another country and label their products in that country’s language. Most manufacturers labeled their products in English, and an international version of their product would be labeled in two to three other languages.
In 1993, when the European Union MDD (93/42/EEC) stipulated that medical device packaging include instructions for use in the packaging for every device in the languages of the countries in which it would be placed on the market, the simplicity and comfort of English-only labeling became history.
There was a five-year transition period to implement the MDD, but most companies either had no clue about the requirements or waited until the last minute to become compliant.
As additional member countries join the European Union (EU) and other regions around the world implement their own labeling requirements, the roles of packaging engineers and regulatory professionals are not to be envied. Requirements mandated by the MDD for labeling include:
- Device name.
- Name and address of manufacturer.
- Name and address of authorized representative.
- Statement indicating in vitro use (when appropriate).
- "Use before" date.
- Batch code preceded by lot or serial number.
- The words "for performance evaluation only" (when appropriate).
- The word "sterile" and method of sterilization (when appropriate).
- The words "self-testing" (when appropriate).
- Intended purpose (if not obvious to user).
- Special storage, handling or operating instructions.
Today, there are 27 member states in the EU and at least another three candidate countries. These countries and their official 24 language requirements can be found in Table 1. As other countries become part of the EU, there will be additional language requirements.
Other European language requirements include countries in the European Free Trade Association (EFTA). Liechtenstein requires translation into German, and Switzerland has requirements for translations into its official languages: German, French and Italian. Multiply those requirements for Asia, and it becomes clear a company will need a package that is at least four feet long to include everything that is required if it wants to sell its device around the world.
Aside from the space limitations of most medical device packaging, manufacturers face several other challenges. It now takes much longer to implement a labeling change because everything must be translated and certified. Those translations are not cheap, and translation expenses become a large item in a company’s annual budget. It might take a year or longer to get a minor labeling change out to customers.
One way to address this problem is through the use of symbols, thus reducing translation time and costs while saving valuable packaging real estate. Symbols visually enhance the label and allow for the addition of languages without major redesign to the printing software or the actual label itself.
With the FDA’s decision to allow symbols only, there is some relief from the onerous requirements and sheer volume of text that had once been necessary. Some of the most commonly recognized and accepted symbols defined in the harmonized section of EN 980 ("Symbols for Use in the Labeling of Medical Devices") are shown in Table 2.
Practices make perfect
Recommended best practices include understanding the requirements, developing a global labeling strategy, developing a long-term language strategy, designing appropriate labels, translating intelligently and carefully, and ensuring appropriate tools and support.
Understanding the requirements. Successful device manufacturers emphasize satisfying the regulatory and the derived requirements. Even though a country may not stipulate the translation of labeling, end users may require it.
Understand your market entry strategy, and consider market opportunities. This includes understanding how many markets are under consideration, what labeling requirements exist or are likely to be enacted and what your competitors are doing.
Developing a global labeling strategy. The best strategy is to use symbols whenever possible. This has become a lot easier since FDA recognized the use of symbols without text. Coupled with the use of symbols, determine the best approach for your company, which could include:
- Using the same label for all markets. This may not, however, be possible because of limited print space.
- Using single-language labels for each country. This will often solve the space problem but will have tremendous cost, manufacturing and inventory implications.
- Keeping inventory unlabeled until an order is received, and then labeling it according to the requirements for the order. But this is time-consuming and expensive, and it has the potential to create inventory discrepancies and could result in misbranding of the medical device.
- Using a combined approach by printing three languages on the label and leaving space for a fourth language that can be applied as a separate label at the time of order. This is called "overlabeling."
There isn’t one correct strategy. You need to determine what is best for your company. Regardless of the approach that you select, however, don’t forget about additional future languages.
Developing a long-term language strategy. Consider country-by-country sales for each product, along with market entry plans and competitive pressures.
Designing appropriate labels. Design effective labels that are easy to use, beginning with standard templates that can be used across products, configurations and markets. This will result in a consistent look and feel on labels and will assist the customer with product selection.
Use icons and symbols, preferably harmonized symbols, whenever possible. Text that alternates between languages is confusing and irritating to users. So, when possible, text for one language should be grouped and appear in the same place from package to package. Use fourth-grade vocabulary and simple declarative sentences. Minimize the use of medical terminology. Keep things simple, but don’t overlook branding implications.
Translating intelligently and carefully. Consider developing a labeling database. Don’t guess at the spelling or word use of text you don’t know. Remember that each language behaves differently in different contexts. You don’t want your labeling to contain typos or look as if a machine translated the text.
When submitting labels for translation, batch them whenever possible to minimize charges. Translate labels with package inserts or instructions for use to ensure consistency of the translated text and to minimize the potential for introduction of linguistic inconsistencies.
Provide the translators with PDF files or other proofs of the formatted label to make it easier to understand what you want the label to say. Looking at only a few words pulled from the label makes it difficult for the translator.
Ensuring appropriate tools and support. Be certain databases, websites and e-mail systems can handle non-English characters. Communication among marketing, regulatory affairs, translation subcontractors and printers need to be frequent, clear and consistent.
Japan’s new PAL
Following the implementation of the new Pharmaceutical Affairs Law (PAL) in Japan, companies registering and marketing their products there face new regulations, including the requirement to appoint a marketing authorization holder (MAH) and changes in the labeling of medical devices.
Under PAL, the Ministry of Health, Labor and Welfare (MHLW) requires the following new information be listed on the product insert for all medical devices:
- The classification of the medical device.
- The address of the MAH.
- The contact information, which must be the location where the marketing of the product is handled.
- The location of the manufacturing site for all devices manufactured overseas.
Complying with international labeling requirements is laborious but not impossible. Good communications, appropriate planning and common sense will significantly reduce the burden and will keep your products from potentially being misbranded.
- Food and Drug Administration, "Federal Food,
Drug and Cosmetic Act," www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct
Les Schnoll has 30 years of experience in industries regulated by the U.S. Food and Drug Administration and is vice president of quality and regulatory affairs for ThermoGenesis Corp. in Rancho Cordoba, CA. He is a senior member of ASQ and is an ASQ-certified quality engineer, auditor and manager. A member of the U.S. technical advisory group to ISO technical committee 176, Schnoll wrote The Regulatory Compliance Almanac (Paton Press, 2001, 2008).