RFID in the Pharmaceutical Supply Chain: Regulations, Physical Limitations and a Real-Life Study

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2 RFID in the Pharmaceutical Supply Chain: Regulations, Physical Limitations and a Real-Life Study Ismail Uysal, Ph.D. Jean-Pierre Emond, Ph.D. College of Technology and Innovation

3 Today s agenda RFID lab at the University of South Florida Polytechnic and what we do Latest guidance and regulations concerning RFID and pharmaceuticals The big Q: is RFID safe for biologics? Hypothesis says yes! But how to test? And what are the final results?

4 Our lab: RFID in transportation

5 Our lab: RFID in sensory monitoring

6 Our lab: RFID in pharmaceuticals

7 What does RFID mean for pharmaceuticals? RFID is currently in use in many different industries and growing even faster since 2003 Many applications in tagging and tracking temperature sensitive products A major shift in pharmaceutical industry from simple barcodes to 2D data matrices and RFID tags Track-n-Trace (TnT) Serialization E-pedigree

8 What is the problem then? RFID cannot be used for biopharmaceutical supply chain Where it can provide the most benefits! Two main reasons: Non-thermal effects of RF radiation on biologics not well-documented A very comprehensive study on blood bags using MHz high frequency radiation by Clive Hohberger, Ph.D. and University of Wisconsin FDA will not allow it per CPG

9 FDA regulations and guidance on RFID Guidance vs. regulations Regulations are based on laws under which FDA operates and are considered and enforced as federal laws FDA guidance describes agency s current thinking on a regulatory issue and is not legally binding on the public or FDA until it is included in a regulation

10 Code of Federal Regulations CFR Title 21 Food and Drugs (1499 parts)

11 CFR Title 21 and RFID A text search of radiofrequency returns: A text search of RFID returns nothing.

12 How does FDA handle newer issues? When there is not enough direction/granularity in the CFR, two popular tools: Points-to-consider (or PTC) mainly for biological manufacturing guidance Compliance policy guides (or CPG) for various items, including new technologies such as RFID and other identification systems

13 Compliance Policy Guides Sec Describes how FDA intends to exercise their enforcement discretion on certain regulatory requirements applicable to RFID studies with drugs Many parameters related to an RFID study are defined in the policy guide such as; Number of tags that can be used (no limit) Type of tags Purpose of study Type of information that can be stored in tags Frequency bands that can be used Type of drugs

14 Compliance Policy Guides Sec Type of drugs? The drugs involved will be limited to prescription or over-the-counter finished products. (OK) The drugs involved will not include those approved under a BLA or protein drugs covered by NDA. (Not OK) The catch? Unless the RFID study is in compliance with all the parameters listed in the guidance FDA intends to exercise enforcement by initiating a regulatory action!

15 Latest guidance concerning RFID (and other technologies) CPG Pro-RFID Limits use on biopharmaceuticals FDA Guidance for Industry final guidance Standards for securing the drug supply chain standardized numerical identification for drug packages March 2010

16 Final guidance for industry Recommends a standardized numerical identifier (SNI) and how it s structured Unique serial numbers for each product package Combined with National Drug Code For products with no NDCs, such as blood products, human tissues, etc. use ISBT128 instead of NDC

17 Final guidance for industry Compatible with GTIN Both human and machine-readable forms Several candidate technologies (RFID, 2D barcode) are mentioned but none recommended!

18 Effects of RF on biologics Thermal effects Studied extensively One good example by H. Bassen of FDA: Liquid Pharmaceuticals and 915 MHz Radiofrequency Identification Systems, Worst Case Heating and Induced Electric Fields, RFID Journal W power instead of 1-4W typical RFID power Worst case scenario 1.7 C temperature rise in the position of maximum effect insignificant

19 Non-thermal effects of RF on biologics Extensive studies on blood bags at MHz Clive Hohberger, Ph.D., Design of a MHz segmented Helmholtz coil for RF exposure testing of biologics to simulated RFID readers, Int. J. RFID Tech. and App., 2009 Packed red blood cells at 4C and agitated whole blood derived derived platelet bags at 24C (controlled temperature) 24 hours at an extreme 5A / m magnetic field strength Result: no adverse effect on either product

20 What about other frequencies and biopharmaceuticals? Some risk assessment studies are done but no true experimental literature Who should be involved (companies)? What to test (types of drugs)? What to expect? (hypothesis) How to test (frequencies, protocol)?

21 Participants Ismail Uysal (University of South Florida Polytechnic) Jean-Pierre Emond (USFP) Price William Dehay (USF, now a medical student) Erdem Altunbas (Borda, an RFID technology company) R. Scott Rasmussen (Abbott) David Ulrich (Abbott) Stephanie Jones (Abbott) Benjamin Zatlin (Abbott)

22 Participating companies Abbott Pfizer EMD Serono Merck Sanofi Pasteur Amgen Pharmaceuticals Schering-Plough GlaxoSmithKline

23 What to test? Categorized biopharmaceuticals into 3 categories: Vaccines easily denatured Immunoglobulin complex structures Hormones potent compounds

24 What to expect? RF waves are part of a broad electromagnetic spectrum Naturally occurring RF energy is everywhere with visible light having magnitudes of energy higher per photon

25 Typical protein size: 50 Å What to expect?

26 Some science behind it Speed of light: 3x10 8 m/s Gamma radiation frequency: Hz Typical highest RFID frequency: 2.4 GHz

27 What to expect? From the protein s point of view the RF wave would not look like a wave at all! Expected => no non-heat effect

28 How to test? Important test criteria Test all commonly used RF frequencies MHz, 433 MHz, 868 MHz, 915 MHz, 2.4 GHz Test at a power level twice the limit regulated by FCC 8W at the antenna output compared to 4W FCC limit 24 hour exposure for a worst case scenario Drug package left in maximum exposure field of the antenna for 3 full work shifts

29 How to test? Dark anechoic test chamber No outside RF radiation Temperature controlled and validated Dark for light sensitive products to prevent photo stability issues High power RF generating hardware RF lucent adjustable fixture to house RF antennas and biopharmaceutical products How will the protein products be analyzed? Stability indicating assays like HPLC Each company might use different analysis technique

30 RF Hardware

31 Antenna side

32 Housing fixture Must be RF-lucent Height adjustable parallel planes to place antennas and products Bottom plane products Top plane antenna facing the products

33 Test chamber Temperature controlled cold room Temperature validated All surfaces covered High performance broadband anechoic material called ECCOSORB: RF-proof Completely dark with chamber door closed

34 Protocol For each product 7 samples are needed: 1 sample kept at the company as the ultimate control sample 1 sample kept at the university but not exposed to RF and sent back with the other samples 5 samples are exposed to RF, 1 per frequency

35 Protocol 5 exposed and 1 non-exposed samples are compared to ultimate control sample: Structure intact for all samples NO EFFECT Structure intact for the non-exposed sample but not intact for exposed sample RF EFFECT Structure non intact for non-exposed sample REPEAT EXPERIMENT

36 Protocol 1) Sample shipped by company to university with non- RF temperature loggers. 2) University checks temperature log data to confirm product stayed within required temperature range 3) Temperature controlled anechoic chamber validated 4) Sample is placed on the RF-lucent table (20cm from antenna after calculations) 5) Chamber is sealed, RF hardware turned on. 6) Signal generator output level is adjusted to appropriate power level. 7) Check spectrum analyzer for RF signal power.

37 Protocol 8) Run the test for a full 24 hour duration. 9) Ship products back to company with non-rf temperature loggers. 10) Company checks temperature log data to confirm product stayed within required temperature range 11) Company administers the protein purity test for the sample. 12) Results are sent back to university in a pass-fail format for each product.

38 Results The study was initiated in Tested more than 100 products. We received the last set of protein analysis data from our participating pharmaceutical companies at the end of 2010.

39 Results In theory RF energy is low Literature shows no significant heat gain Our results show no non-heat effect

40 Discussion It was most important to have a universally applicable testing protocol and, As many different protein types and products as possible! Results match theory RFID is safe for biopharmaceutical supply chain

41 RFID in pharmaceutical supply chain a real life study Goal: to improve efficiency of an RFID implementation on a pharmaceutical company s assembly lane Approach: a methodical and statistical approach to parametric analysis for improved efficiency Problems: cannot stop factory operation for system modification, too many performance modifiers

42 Today s RFID systems Too many system parameters with significant effects on performance Low level reader protocol (LLRP) Great control but too many choices RF link profiles, duty cycles, RF output power, antenna sequence, etc. Physical parameters Tag location on product Antenna placement, etc.

43 Solution: fully automated, RFID enabled closed loop conveyor State-of-the-art conveyor belt to mimic real life packaging lanes for pharmaceuticals

44 Important features Modular design Enables mounting of different readers, antennas, etc. Removable sides allow for realistic simulation of the actual conveyor in the plant Different material choices Other unique characteristics for each lane Metering station to mimic true product flow Completely automated with configurable test schedules

45 Important features Closed-loop system for highest statistical significance with no human interruption Tests can run for an unlimited time for reliable and comprehensive parametric testing Intelligent RFID software Systematic cycling and modification of all RFID system parameters Comprehensive results documentation for decision making Compatible with all RFID technologies and current protocols

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