Code compliance

Under 21 CFR Parts 201, 606 and 610, the FDA requires certain human drug and biological product labels to carry linear barcodes containing the NDC number. Sherwood Technology has adapted its DataLase technology to comply with the FDA ruling

The American Hospitals Association¹ cites the failure to insert appropriate labelling as a drug is prepared and repackaged into smaller units as one of the key causes of medication errors.

To reduce the number of medication errors in hospitals and healthcare settings (where the FDA has no jurisdiction), the FDA published the final version of the 21 CFR Parts 201,606 and 610 on 25 February, 2004.

The FDA was influenced to propose this rule because of the increasing number of deaths associated with medication errors - they account for one out of 131 outpatient deaths and one out of 854 inpatient deaths². FDA estimates that the rule will help prevent nearly 500,000 adverse events and transfusion errors while saving US$93bn to the US economy in health costs over 20 years.

The FDA also aims to influence hospitals to implement Medication Administrations Recording (MAR) Systems - patient drug regimen in a computerised database - that use barcode scanning. This will enable healthcare professionals to use scanning equipment to verify that the right drug, in the right dose and right route of administration, is being given to the right patient at the right time.

machine-readable labels

The rule proposes that all prescription drug products (except animal drugs) and prescription biological products (e.g. vaccines) be labelled with a barcode. Blood and blood products (excluding physician samples) must have machine-readable information on the container label. The code must have a National Drug Code (NDC) number, which can be contained in an International Article Number (EAN), a Universal Product Code Number (UPC) or comply with HIBCC standards (Health Industry Barcode standards).

The barcode must appear on the drug's immediate container label as well as the outer wrapper or container unless the barcode is easily legible and machine-readable through the external wrapping. The rule applies to manufacturers, repackagers, relabellers and private label distributors who are not exempt from the established registration and drug listing requirements of the laws behind the FDA.

Generally, compliance with the rule has to take place within 60 days after publication in the Federal Register. However, if a drug receives approval on or after the effective date, it must comply with the barcode requirement within 60 days of the drug's approval date. If the drug was approved prior to enactment of the rule, the drug must comply within two years of the final rule's effective date.

A few fears have arisen concerning the rule. For example, one comment cited in the official FDA document² described problems associated with installing new barcoding technology in old buildings. Another FDA comment addressed drugs that are supposed to remain sterile and are packaged in trays (thus they should remain in the packaged tray until use). By requiring a barcode on the immediate wrapper, there is a risk that the drug will become contaminated during the barcoding process.

Traditionally, barcoding methods are chosen according to the type of data to be included in the barcode, the amount of printing space available, and the required location of the barcode - if it is near an edge then there is a risk of misreads, meaning that it cannot be read by a scanner.

printing options

These methods tend to use laser, ink-jet, thermal or dot matrix printers. The FDA commented that although inkjet and thermal printers may be appropriate for production line barcode printing, they can cause difficulties in print speed, resolution and media compatibility. Water-based inkjet fluids have a tendency to streak and blur, while non-water soluble inkjet fluids produce a shine that reflects to the scanner and affects how the barcode is read. Desktop laser printers are subject to toner flaking, which makes them unreliable for long-term barcode printing.

More recently, laser marking systems have been deployed which use a high powered beam to ablate the barcode onto the label by 'burning' away a black ink patch to form the white spaces by exposing the underlying substrate material. Emission levels tend to be high as the ink layer has to be completely removed to produce the barcode image. With laser ablation, production line speeds may also create problems for barcode resolution levels.

Sherwood Technology, of Widnes in the UK, has come up with a novel solution to comply with the FDA's rule. The company has developed DataLase, a non-toxic and environmentally friendly ink, coating, or substrate additive that produces a positive image when marked by a low power CO2 laser. The ink, coating or additive undergoes a simple chemical colour change and creates an image - barcode - that is stable and has high contrast. Compared with more traditional coding and marking processes, it also has a higher fidelity.

permanent image

Imaging can also be formed through polypropylene and polyethylene films, allowing an indelible laser marked barcode to be permanently embedded or 'sandwiched' in laminates (unlike conventional surface printing that can be unintentionally removed or damaged). Such a system falls eminently in line with the rule that requires the barcode to remain intact under 'normal conditions' (rule sec 201.25 (c) (1) (i)).

This is of profound significance considering the potential for adverse processing and environmental influences on the code from its formation to the eventual patient drug administration. Although not explicitly required by the ruling, a further benefit of encapsulating the code by this method is that it bestows an additional feature of tamper resistance and tamper evidence.

The laser-responsive DataLase additive can be applied to the substrate by a variety of methods, although the most common in the pharmaceutical sector would be to use the existing label or packaging printing method to apply a registered patch of DataLase ink. The laser-responsive patch is subsequently activated (imaged) using a low power 'steered beam' CO₂ laser which forms the linear bar code even through an overlaminated film as detailed above. The DataLase patch changes colour from neutral to black where exposed to the laser beam, thereby producing an indelible, permanent mark that does not smear, peel or fade away.

The coding process uses very low power at high speed. This offers substantial advantages over other commercially available methods, including low emission, high throughput, increased productivity, compliance with environmental regulations, and improved quality.

The barcode contrast and image clarity benefit from the laser imaging process, as an extremely small, fine laser beam is used which gives an extremely precise code, with no 'spreading' of the line-width. This translates into a much higher success rate on scanning the codes in the field.

Indeed, a distinguishing feature of this technology is the ability to produce extremely high resolution images. This translates into much higher definition one-dimensional and two-dimensional barcodes, carrying a greater amount of data per unit area than is currently possible with conventional printing methods. For example 2-D codes as small as 2mm2 can be marked onto the laser-responsive patch, scanned and read without problem.

The FDA welcomes such initiatives, commenting in the ruling: 'We decline to exempt small vials or containers (including suppositories, prefilled syringes, and other small products for which comments sought exemptions). We agree that the risk of medication errors for these products cannot be ignored, and we also find the UCC's comments persuasive. If several pharmaceutical companies have already shown their ability to place a barcode on a 1mL vial, we cannot justify a blanket exemption for comparatively larger products, such as 5mL vials and prefilled syringes.'

DataLase provides a means of barcode printing without ablation, and without the use of transfer ribbons or fluids at the point of coding, but rather by causing a change of colour in the substrate on the application of laser energy on which the printing is to appear.

The chemistry is a viable alternative to traditional barcoding methods by abolishing the problems associated with the apparatus i.e. ribbons, fluids, solvents, maintenance, unreliability etc which are particularly undesirable where sensitive pharmaceutical products are packaged.

higher productivity

'DataLase is set to revolutionise the printing of codes and markings in areas where traditional techniques have remained stagnant and offer very limited future development opportunities,' says Steve Kelly, managing director of Sherwood Technology.

'The technology offers anticounterfeiting properties as well as the potential for producing very small and accurate barcodes. Pharmaceutical manufacturers, relabellers and repackagers will be able to achieve higher productivity levels, better control over the barcoding of pharmaceutical products and compliance with 21 CFR Parts 201, 606 and 610.'