Serialization’s a Comin’!
Serialization is to play a huge role in reducing the global proliferation of substandard, spurious, falsely-labeled, falsified, and counterfeit (SSFFC) drugs. SSFFC drugs can lack active ingredients, include incorrect ingredients, not have enough active ingredients, or even have too much of an active ingredient. Due to the clandestine and illegal nature of the manufacture and distribution of SSFFC drugs, the global breadth and scope the SSFFC problem is hard to quantify and harder still to contain and stop. What "IS" known is the public health risks of using SSFFC drugs. Here are a few:
• Illness or injury treatment failure
• Increased resistance to disease or virus infection
• Sickness and death
What is Serialization?
Typically, an individual drug carton has a label with the drug name, company’s name (or logo), lot number, and expiration date. In order to prevent SSFFC drugs from being manufactured, distributed, and used there must be a way to determine that a drug ‘unit’ (an example would be a small carton containing a bottle of eye drops) was made by the drug manufacturer listed on the label and that the contents match the label. Other than looking at the label (which could be a counterfeit), how can anyone really know that the drug is what the carton and label say it is? An electronic pedigree (e-pedigree) is one way to really know.
An e-pedigree is a verifiable file that tracks the ownership of a drug from initial manufacture through the supply and distribution chain all the way to a pharmacy, hospital, or doctor’s office. This e-pedigree also includes returns, recalls, and the proper disposal of drugs that have passed the expiration date. In order for the e-pedigree to be effective, it must track and trace the drug down to the smallest package or saleable unit/carton. In this manner regulating agencies can determine not only where a unit/carton originated, who had it and when, but can also identify if a counterfeit unit/carton was inserted in the supply and distribution chain.
What is the mechanism to differentiate each individual package or saleable unit/carton from each other? One mechanism is Radio Frequency Identification (RFID) tags. RFID tags can certainly provide the ability to track and trace an individual unit, and RFID information on unit/carton whereabouts can be added to an e-pedigree; however, an RFID solution requires special equipment to make and program the RFID tag, affix the RFID tag to the unit/carton, and read and track the RFID tag at points in the packaging line. The orientation of the tag placement - as well as the tag reader with respect to the tag placement as it traverses the line - is also critical. In order to make a determination of the validity of the unit/carton later in the distribution chain, an RFID tag reader would be required.
Serialization is the generation of a unique identification number that is added to the unit/carton, case, and pallet labels in the packaging line. The inspection stations keep track of the individual serial numbers on the unit/cartons and provide that information to the track and trace e-pedigree system. Although a serialization e-pedigree solution will be costly to implement, the cost impact is mitigated by the fact that packaging line printers and inspection stations already exist; labels are already being affixed to cartons, cases, and pallets.
How Does Serialization Work?
Numbers are generated at the enterprise level and provided to the serialization system. The serialization system can be integrated into the Packaging/Manufacturing Execution System (PES/MES) or can be a stand-alone system that works alongside the packaging line. The numbers generated must be unique and conform to standards such as GTIN (Global Trade Item Number) and the serialized National Drug Code (sNDC). Fortunately, the advent of 2-D coding (instead of the standard bar code) allows large numbers to be coded into a relatively small space.
Once the serialization system receives the unique identifying number it provides the number to the case labeler printer where it is added to the case label. Once printed and affixed to the case, the case label is inspected as it normally would be on a packaging line, however, now the unique identifying number is also verified, reported back to the serialization system as being used, and time-stamped in the e-pedigree database. This process is repeated as cases are loaded into cartons, and cartons onto pallets. As each number is used on case, carton, and pallet labels the numbers are verified used and reported back to the serialization system. These serialized cases, cartons, and pallets are then used in the specific electronic pedigree for each drug unit/carton. Used and unused numbers are passed back up to the enterprise level ‘Number Generation Module’ so that used numbers can be ‘retired’ and unused numbers can be used on a different production run.
Who’s Making E-Pedigree Law?
In the US, the state of California is first to arrive with the following legislation (www.pharmacy.ca.gov):
“California’s e-pedigree requirements for prescription drugs will take effect on a staggered basis from January 1, 2015 through July 1, 2017. Changes enacted by SB 1307 (Ridley-Thomas, Chapter 713, Statutes of 2008) instituted the following implementation compliance date schedule:
• 50% of a manufacturer’s products by 2015;
• The remaining 50% of the manufacturer’s products by 2016;
• Wholesalers and repackagers must accept and forward products with the e-pedigree by July 1, 2016; and
• Pharmacy and pharmacy warehouses must accept and pass e-pedigrees by July 1, 2017.”
The FDA is not far behind with specific legislation in the works; however, how federal legislation will impact – or supersede - California’s e-pedigree requirements remains unclear. Turkey and France both have enacted e-pedigree program laws. Germany and Brazil have them in the works, and other G20’s are following suit. In addition to patient safety, a contributing factor to the EU speed of e-pedigree adoption is the fact that medical reimbursements are submitted and processed through the respective country’s health care system(s). All e-pedigree and drug traceability processes should help to reduce medical reimbursement process fraud.
Are There Other Benefits to Serialization?
There are quite a few. The following are important ones:
• The ability to ‘see’ which drug went where, when, and to who would assist in creating transparency in the wholesale drug distribution network and would help sharpen the ability to forecast demand. It can provide feedback data for past marketing programs.
• If a non-serialized drug shipment is stolen, the company would have to recall the entire lot since the stolen drug could be adulterated in some way (such as taking a single unit dose and diluting it to increase the number of doses to sell) and then re-introduced into the supply chain. If the drug were serialized, it would be easy to determine which ones are the ‘good’ ones and which are not.
• In an actual recall scenario (where a company has legitimate recall reasons), finding the units for recall could be a simple database search.
• Many drugs have rebates or fees associated with them when purchased through government healthcare programs (i.e., Medicare). The ability to track and trace specific Units at the point of sale/use will allow companies to keep track of (and report) these rebates or fees.
Guidance for Industry Standards for Securing the Drug Supply Chain - Standardized Numerical Identification for Prescription Drug Packages – FDA, March 2010