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U.S. Department of Health and Human Services

Drugs

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Counterfeit Drug Task Report February 2004 Update - TECHNOLOGY

A. Unit of Use Packaging

  1. What FDA sought comment on:
    Whether to package all finished dosage form drugs in unit of use packaging as appropriate for the particular product (e.g., tablet, multi-dose vial) at the point of manufacture
  2. What the comments said: Comments cited a large number of benefits, including eliminating the need for re-packaging and improved patient compliance, as well as a large number of costs, including those associated with shifting production from bulk packaging. The cost hurdle to counterfeiters, created by unit of use packaging, was said not to be high enough for it to be effective as a stand-alone anti-counterfeiting measure. A detailed discussion of the comments is in Appendix B.
  3. Discussion: Although single unit containers (e.g., blister packs) usually come to mind, unit of use packaging is any container closure system designed to hold a specific quantity of drug product for a specific use and dispensed to a patient without any modification except for the addition of appropriate labeling.
    Unit of use packaging does not create a sufficiently high level of security to justify its use as a stand-alone anti-counterfeiting measure. However, because of its many other benefits, which may vary on a product specific basis (e.g., tablets, liquid forms), manufacturer initiated cost-benefit analyses of particular products, starting with newly approved products and products that are likely to be counterfeited, are likely to show that unit of use packaging could be effective as one layer in a multi-layered anti-counterfeiting strategy.
  4. FDA Conclusions:
  5. Unit of use packaging can be beneficial in fighting counterfeit drugs.

    • It would be beneficial for all manufacturers and re-packagers to analyze the costs and benefits of using unit of use packaging for each product, starting with newly approved products and products that are likely to be counterfeited, and to consider implementing unit of use packaging for products where the benefits are equal to or outweigh the costs;
    • Unit of use packaging can be helpful, but only as one layer in a multi-layered anti-counterfeiting strategy;
    • FDA intends to encourage adoption of unit of use packaging by: inviting stakeholders and other interested individuals and organizations to submit research on the relative costs and benefits of unit of use packaging to assist FDA in developing future policy; and encouraging standard setting bodies to develop standards for unit of use packaging with the goal of reducing its costs (e.g., in areas such as size, shape, and pill organization).

B. Tamper Evident Packaging

  1. What FDA sought comment on:
    Whether to use tamper evident packaging from the point of manufacture, for all dosage forms, active pharmaceutical ingredients (APIs), and bulk chemicals?
  2. What the comments said:
    The comments on tamper evident packaging mirrored the comments on unit of use packaging.
  3. Discussion
    Decisions to employ tamper evident packaging on prescription drug containers as an anti-counterfeiting measure require a product specific cost-benefit analysis. As with unit of use packaging, FDA does not believe that tamper evident packaging presents a high enough hurdle for counterfeiters to make it effective as a stand-alone anti-counterfeiting measure.
  4. FDA Conclusions:
  5. Tamper evident packaging may be beneficial in fighting counterfeiting of prescription drugs.
    • It would be beneficial for manufacturers and re-packagers to consider using tamper evident packaging for prescription product containers, starting with products likely to be counterfeited or newly approved products, where the benefits are equal to or outweigh the costs;
    • Tamper evident packing can be helpful, but only as one layer in a multi-layered anti-counterfeiting strategy.

C. Authentication Technology

  1. What FDA sought comment on:
    • Whether to incorporate at least two types of anti-counterfeiting technologies into the packaging and labeling of all drugs, at the point of manufacture, with at least one of those technologies being covert (i.e., not made public, and requiring special equipment or knowledge for detection) starting with those products at high risk of being counterfeited and where the introduction of counterfeit product poses a serious health risk;
    • Whether to incorporate a taggant, chemical marker, or other unique characteristic(s) into the manufacturing process of all drugs that is only identifiable with the use of sophisticated analytic techniques starting with those products at high risk of being counterfeited and where the introduction of counterfeit product poses a serious health risk; and
    • Whether to issue FDA guidances concerning the appropriate use of anti-counterfeiting technologies and the application and review process for labeling and packaging changes or product changes such as incorporation of taggants, chemical markers, or other unique characteristic(s) into the product for the purpose of product authentication.
  2. What the comments said:

    The comments stressed that there was no "silver bullet" anti-counterfeiting technology because sophisticated, well-financed counterfeiters can defeat any anti-counterfeiting measure. Therefore, the best strategy is to use multiple, periodically changing, authentication measures on a product specific basis after doing a risk analysis that takes into account the risk that the product will be counterfeited and the public health risk if the product is counterfeited.

    Given the rapid developments in anti-counterfeiting technology and the dangers of aiding counterfeiters by locking in or requiring certain technologies, most comments stressed that the FDA should not mandate the use of specific anti-counterfeiting technologies.

    FDA issuance of guidance concerning the agency's application and notification policies and procedures related to incorporating anti-counterfeiting measures into products (e.g., taggants) or labeling and packaging (e.g., inks, holograms) was universally supported.

    A detailed discussion of the comments is in Appendix B.

  3. Discussion:

    FDA agrees that the danger of unwittingly assisting counterfeiters and stifling technologic development outweigh the benefits that would accrue if it were to mandate the use of a specific authentication technology at this time. Furthermore, the decision to deploy authentication technologies is best made by the manufacturer, based on a product specific risk-benefit analysis that, in the future, should take into account whether mass serialization and radio-frequency identification technology (see below) is being used for tracking and tracing the drug.

    However, due to the high costs and technical barriers that authentication technologies create for counterfeiters, their use is a critical component of any effective multi-layered anti-counterfeiting strategy, especially for products that are likely to be counterfeited. Therefore, FDA believes that an appropriate role for it is to facilitate the use of authentication technologies by reducing any regulatory hurdles that may exist relating to their use.

  4. FDA Conclusions:
  5. Existing authentication technologies have been sufficiently perfected they can now serve as a critical component of any strategy to protect products against counterfeiting.
    • The use by manufacturers and re-packagers of one or more authentication technologies on their products, particularly those likely to be counterfeited, would protect the public health and diminish counterfeiting;
    • To facilitate the use of authentication technologies on existing products, FDA plans to publish a draft guidance on notification procedures for making changes to products (e.g., addition of taggants), their packaging, or their labeling for the purpose of deterring and detecting counterfeit drugs;
    • FDA plans to continue to evaluate and disseminate information to stakeholders on developing forensic technologies (e.g., use of product fingerprinting, addition of markers) and other analytical methods that allow for rapid authentication of drug products.

D. Identification of Products likely to be counterfeited

  1. What FDA sought comment on:
    • Are all products at high risk for being counterfeited?
    • How can products at high risk for being counterfeited be identified?
    • What criteria should be used to determine if a product is at high risk for being counterfeited?
  2. What the comments said:
    Although a few comments suggested that all products were at high risk for being counterfeited, most of the comments FDA received supported the idea of developing criteria by which stakeholders could determine which products are likely to be counterfeited and/or developing a national list of products likely to be counterfeited based on these criteria. There was general agreement that the existence of state specific lists, each with its own regulatory requirements, could inhibit commerce and adversely affect the availability of drugs. FDA notes that the State of Florida has already published a list of "specified products" (i.e., a list of drugs most likely to be counterfeited) that is being used to implement state pedigree requirements. A detailed discussion of the comments is in Appendix B.
  3. Discussion:
    Due to the large number of drugs with the potential to be counterfeited, FDA does not believe it is possible to create a comprehensive list of all such drugs. However, FDA does believe that a national list of those drugs most likely to be counterfeited and/or a set of criteria to use for determining those drugs would be useful for stakeholders to use at their discretion. Uses could include:
    • Assisting manufacturers and re-packagers in making decisions whether to use authentication technologies and unit of use packaging;
    • Assisting wholesalers in developing purchasing policies and allocating resources for detecting counterfeits;
    • Assisting retailers in targeting certain drugs for authentication and patient education prior to dispensing;
    • Assisting states in implementing regulatory requirements;
    • Assisting stakeholders in developing migratory paths to adoption of mass serialization and electronic track and trace technology.
    • FDA strongly supports the development of such a set of criteria, or a list based on these criteria, that has the support and participation of all stakeholders. Regular input from interested parties as well as the ability to add or delete drugs from the list on short notice are important parts of the process.

      FDA believes that members of regulated industry are better positioned at this time than FDA to develop a process for creating, maintaining, and updating such a list (and/or set of criteria).

  4. FDA Conclusions:
  5. FDA has concluded that there would be great value in the creation of a national list of drugs most likely to be counterfeited based on factors that are likely to contribute to counterfeiting risk.

    • FDA intends to encourage stakeholders and standards setting organizations to work together to create a national list of drugs most likely to be counterfeited, based on an assessment of criteria for determining counterfeit risk;
    • The best result would be achieved if all stakeholders, including FDA, and other interested parties participate in developing a list, or criteria for determining, drugs most likely to be counterfeited;
    • Any such list, and/or criteria, would be most effective if made publicly available to all stakeholders.

FDA is aware of only one national list of drugs most likely to be counterfeited. The list was developed by the National Association of Boards of Pharmacy and is available at www.nabp.net.

E. Radio-frequency Identification (RFID) Technology 

  1. What FDA sought comment on:
    • Whether a pedigree for all drug products can be achieved by phasing in track and trace technology (i.e., electronic pedigree) starting at a case and pallet level for products likely to be counterfeited and progressively including all products at the case, pallet, and package level; and
    • Whether, as an interim measure, prior to widespread adoption of track and trace technology all drugs and biologics likely to be counterfeited should be tracked and traced either by limiting the number of transactions of the product or by using available track and trace technology, identifying the drug at the case and pallet level, and preferably at the product level, throughout the distribution system.
  2. What the comments said:
    There was universal support for the adoption of electronic track and trace technology. RFID was cited as being the technology with the strongest potential for securing the supply chain but that it was not ready for widespread commercial use with pharmaceutical products. Many costs, potential benefits, and unresolved issues related to RFID were cited. The potential benefits included the ability to control inventory and conduct rapid, efficient recalls, while costs that could hinder the adoption of RFID included purchase of tags and other hardware, integration into existing information systems, and compliance with regulatory requirements (e.g., labeling, electronic records). Important unresolved issues included the need to develop standards and business rules for RFID, the need to address database management issues, and the need to determine the effect of RFID on product quality.
    FDA was also informed that some companies are planning feasibility studies concerning business uses of RFID for early this year and that other activities related to creating standards, business rules, and migratory pathways for RFID are also ongoing. A detailed discussion of these activities and other comments concerning RFID is in Appendix B.
  3. Discussion
    Use of mass serialization to uniquely identify all drug products intended for use in the United States is the single most powerful tool available to secure the U. S. drug supply. Mass serialization involves assigning a unique number (the electronic product code or EPC) to each pallet, case, and package of drugs and then using that number to record information about all transactions involving the product, thus providing an electronic pedigree from the point of manufacture to the point of dispensing. This unique number would allow each drug purchaser to immediately determine a drug's authenticity, where it was intended for sale, and whether it was previously dispensed. Although there is general agreement that widespread use of mass serialization is inevitable, several important issues remain unresolved, including the migratory path(s) that participants in the drug distribution system will follow as they begin to serialize their products, and the most likely timeline for widespread commercial use.

    It currently appears that the technology most likely to bring mass serialization into widespread commercial use by the pharmaceutical industry is RFID, although two-dimensional bar codes may be used for some products. RFID technology includes not only the silicon tags containing the EPC, but also antennas, tag readers, and information systems that allow all users to identify each package of drugs and its associated data. This data can be used not only to authenticate drugs but also to manage inventory, conduct rapid, targeted recalls, prevent diversion, and ensure correct dispensing of prescriptions.

    Acquiring and integrating RFID technology into current manufacturing, distribution, and retailing processes will require considerable planning, experience, and investment of resources. Currently, some manufacturers, wholesalers, and retailers are developing business plans and testing mass serialization using RFID while others are taking a wait and see approach. Due to rapid technologic advancements, the lack of significant market place experience with it in the pharmaceutical supply chain, each participant is best situated to determine his optimal path(s) to adopting it. Therefore, FDA has identified near term actions, described below, for it to take in order to facilitate the performance of mass serialization feasibility studies using RFID, and to assist stakeholders as they migrate towards the use of RFID technology. 

    In the long term, after there is significant market place experience with RFID, FDA plans to propose or clarify, as necessary and appropriate, policies and regulatory requirements relating to the use of RFID. Labeling, electronic records, product quality, and Current Good Manufacturing Practices (cGMP) requirements are issues that have arisen in connection with RFID. However, regulatory or policy determinations regarding these, or other, issues should not be made until they can be informed by sufficient data and significant marketplace experience with RFID. FDA has also identified a series of actions, discussed below, that would help industry stakeholders and standard-setting organizations achieve this goal. Lastly, stakeholders will need to ensure that they comply with the patient privacy protections provided by the Health Insurance Portability and Accountability Act as they implement use of RFID technology.
  4. FDA Conclusions:

    The adoption and common use of RFID as the standard track and trace technology, which is feasible in 2007, would provide better protection.

    • Due to industry's current initiatives, mass serialization and RFID technology is likely to be adopted according to the following timeline:

      January - December 2004
    • Performance of mass serialization feasibility studies using RFID on pallets, cases, and packages of pharmaceuticals;

      January - December 2005
    • Mass serialization of some pallets and cases of pharmaceuticals likely to be counterfeited;
    • Mass serialization of some packages of pharmaceuticals likely to be counterfeited; and
    • Acquisition and use of RFID technology (i.e., ability to read and use the information contained in RFID tags and the associated database) by some manufacturers, large wholesalers, some large chain drug stores, and some hospitals.

      January - December 2006
    • Mass serialization of most pallets and cases of pharmaceuticals likely to be counterfeited and some pallets and cases of other pharmaceuticals;
    • Mass serialization of most packages of pharmaceuticals likely to be counterfeited; and
    • Acquisition and use of RFID technology (i.e., ability to read and use the information contained in RFID tags and the associated database) by most manufacturers, most wholesalers, most chain drug stores, most hospitals, and some small retailers.

      January - December 2007
    • Mass serialization of all pallets and cases of pharmaceuticals;
    • Mass serialization of most packages of pharmaceuticals; and
    • Acquisition and use of RFID technology (i.e., ability to read and use the information contained in RFID tags and the associated database) by all manufacturers, all wholesalers, all chain drug stores, all hospitals, and most small retailers.
    • FDA plans to assist, to the extent necessary and appropriate, in facilitating the rapid, widespread adoption of RFID in the drug distribution system by working with stakeholders in the following areas:
      • Addressing any regulatory and policy issues related to the performance of feasibility studies;
      • Addressing any regulatory and policy issues relating to the notification requirements associated with implementation of RFID;
      • Addressing any product quality concerns and data issues related to the performance of feasibility studies;
      • Reviewing protocols for feasibility studies;
      • Working with other governmental agencies to coordinate activities;
      • Encouraging stakeholders to convene meetings of supply chain participants to identify, discuss, and propose solutions to technical, business, and policy issues related to the use of RFID technology in the pharmaceutical distribution system; and
      • Exploring the need for any other processes and venues that might be needed to assist stakeholders as they migrate towards the use of RFID technology.
    • FDA intends to regularly review the pace at which RFID is being adopted in the U.S. drug distribution system;
    • FDA plans to publish or clarify, as appropriate, regulatory requirements, policy guidance, and product quality testing requirements related to the use of RFID after sufficient data and marketplace experience with RFID are available to adequately inform our decision-making; and
    • FDA intends to consider taking further steps to facilitate the adoption of mass serialization.


Business steps for industry

Each industry stakeholder interested in implementing RFID would benefit from the following steps:

    • Create an internal team focused on the adoption of mass serialization and use of RFID technology;
    • Perform internal feasibility studies to gain experience with mass serialization and RFID technology and to identify internal business issues requiring resolution;
    • Perform external pilot studies with stakeholders across the supply chain to gain experience using mass serialization and RFID and to identify opportunities, barriers and external business issues associated with them;
    • Develop policy and a business case for the use of mass serialization and RFID;
    • Cooperate and work with other stakeholders and government agencies to develop infrastructure and information systems to use with mass serialization of pallets, cases, and packages of drugs;
    • Participate on standard setting groups developing technical standards and business rules for use of mass serialization and RFID;
    • Work with government agencies and other members of the supply chain to identify and address regulatory and economic issues that could delay the adoption of mass serialization and RFID; and
    • Educate other members of the supply chain and government agencies about mass serialization and RFID.

To the extent possible, it would be most useful for interested firms to perform these actions concurrently. For example, standards development requires knowledge gained from feasibility studies in order to move forward, and vice versa.


Standards Setting Issues

Any effort to develop standards for mass serialization of pallets, cases, and packages would be most effective if it addressed the following issues:

    • Minimum Information Requirements for the serial number— in the case of RFID tags this means containing a mass serialization code that uniquely identifies the object to which it is attached (e.g., minimum of 96 bits of information);
    • Communication protocol standards— in the case of RFID this means standard protocols for interrogating and reading tags;
    • Reader Requirements—Readers of mass serialization codes should be interoperable (e. g., readers must use protocols that allow them to read multiple classes of tags or bar codes, as applicable) and should be able to automatically upgrade software over an information network;
    • Pedigree requirements—this means that databases containing transaction information should be compatible (e.g., format, mark-up language);
    • Information Network Requirements

      1. Database Structure (e.g., centralized vs. distributive)
      2. Data ownership
      3. Data access (to meet business, track and trace, and recall needs)
      4. Data Access controls to assure information security;
    • Software Requirements—all applications should be compatible and compliant to assure global interoperability; and
    • Best use of Frequencies—(e.g., 13.56 megahertz on packages and 915 megahertz on cases and pallets due to interference and read range issues).