Prescription medicines in Japan

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In many countries and regions, coding rules have been extended in recent years to include variable data introduced by means of machine- readable codes. Machine-readable codes are barcodes and matrix codes. In retail, the EAN barcode (or barcode) with a fixed coded article number is ever-present. For medicinal products, labelling with a Data Matrix Code has been mandatory in Europe since 2019 per Delegated Regulation 2016/161. The Data Matrix Code contains a fixed article number, which is supplemented with variable data (including a serial number). In the USA, the DQSA Act [in Part 2 DSCSA - Drug Supply Chain Security Act, SEC 582, 9(A) (i) and (ii)] made coding with a Data Matrix Code mandatory in 2013. In Russia, a crypto code was introduced in 2018 by Regulation 1556, which was then amended in 2019 by Regulation 1118 and in 2020 by Regulation 311. This is also a Data Matrix Code that includes an article number, serial number and, as a special feature, a crypto code and crypto key.

In Japan, a document on the implementation of "new" barcodes on medicinal products was published in 2006 by the MHWL (the Japanese Ministry of Health, Labour and Welfare), the department responsible for drug and food safety, in the form of Food Safety No. 09 1500 1. The initiative was prompted by the desire to increase patient safety by avoiding mix-ups, as well as to improve the possibilities for traceability. The specifications define the types of medicinal products and the packaging levels concerned.

In some sections, original Japanese texts have been inserted as a reference (https://www.pmda.go.jp/files/000214756.pdf).

The types of medicines are listed as follows:

1. 特定生物由来製品
These are, for example, blood products, blood clotting factors, serum albumin or the like.

2. 生物由来製品(特定生物由来 製品を除く
These are products made from biological starting materials of human or animal origin. Excluded are the products mentioned under 1.

3. 内用薬(生物由来製品を除く
These are medicinal products taken in liquid or solid form.

4. 注射薬
These are medicinal products that are administered by injection.

5. 外用薬
These are topical medicinal products and therefore anything that is applied externally in ointment or liquid form. Nasal sprays and eye drops etc. also fall into this category.

The labelling requirement differs depending on the packaging level.

The first level is 調剤包装単位. These are e.g. blisters, ampoules or similar, i.e. primary packaging.

The second level is the sales packaging (販売包装単位). This contains one or more products from the first level (secondary packaging).

The third level is a single-variety shipping or bundle package consisting of level 2 products (元梱包装単位) (tertiary packaging).

Narcotics do not have to be labelled. Sample packaging is also exempt. Products for clinical trials must be labelled on level 1 (ampoule, blister), but not on the sales packaging. Radiological products must be labelled on the outer packaging (e.g. on the outside of a lead container), but not on the product itself. Gases and extremely deep-frozen products are also exempt.

In all examples and explanations, the batch designation or serial number is always mentioned. There is no requirement that both must be coded. When the batch designation and when the serial number must be used is not clear from the Japanese texts.

The author's assumption: The respective manufacturer defines this with the authorities during approval for the Japanese market.

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Labelling is defined as follows (since 2016):

(1) Blisters, ampoules and similar packaging (primary packaging)

Type of medicinal product

Article number

Expiry date

Serial number or
batch identifier

Product category 1 (biological origin

a

a

a

Product category 2 of biological origin other than those in
category 1

a

b

b

Medicinal products to be taken orally

a

b

b

Medicinal products which are injected (except those in
categories 1 and 2)

a

b

b

Medicinal products for external use

a

b

b

(2) Sales packaging (secondary packaging)

Type of medicinal product

 Article number

Expiry date

Serial number or
batch identifier

Product category 1 (biological origin)

a

a

a

Product category 2 of biological origin other than those in
category 1

a

a

a

Medicinal products to be taken orally

a

c

c

Medicinal products which are injected (except those in
categories 1 and 2)

a

c

c

Medicinal products for external use

a

c

c

(3) Bundles and shipping packages (single-variety) (tertiary packaging)

Type of medicinal product

Article number

Expiry date

Serial number or
batch identifier

Product category 1 (biological origin)

a

a

a

Product category 2 of biological origin other than those in
category 1

a

a

a

Medicinal products to be taken orally

a

c

c

Medicinal products which are injected (except those in
categories 1 and 2)

a

c

c

Medicinal products for external use

a

c

c

Legend:
a: Data that must be provided on a mandatory basis.
b: Data that are not mandatory but may be added voluntarily.
c: Data that are mandatory. In the original version of 2006, this was still optional.

Coding

The following code types (symbologies) are prescribed:

GS1 Databar limited (ISO/IEC 24724)

 

GS1 Databar stacked (ISO/IEC 24724)

 

The GS1 Databar limited and the GS1 Databar stacked can only encode the article number (in this case they must encode a GTIN [see below for an explanation of terms]).

GS1 Databar limited Composite CC-A (ISO/IEC 24724+ ISO/IEC 24723)

 

GS1 Databar stacked Composite CC-A (ISO/IEC 24724 + ISO/IEC 24723)

 

GS1-128 (ISO/IEC 15417)

 

For size comparison: GS1 DataMatrix with the data of the GS1 Databar limited Composite.

Data encodation in the GS1 Databar Composite Code shall use a defined data structure. Each data like article number, bactch or serial number etc. ist consisting of two parts in the code. The first part is called Application Identifier. The Application Identifier is 2, 3 or 4 digits longs (numeric only) and defines the meaning of the following data field (second part). The following text explains this more in detail.

The use of the Application Identifiers (AI) 01, 17 (alternatively 7003), 21, 10 and 30 is prescribed for coding the article number, expiry date, serial number, batch designation and quantity. If AI 7003 is used for the expiry date, the hour and minute for the expiry of the product must be added.

The Application Identifiers give the following data field a fixed meaning and format. This specification enforces the use of the Isssuing Agency GS1 (registered according to ISO/IEC 15459-2). The JAN number is required as the article number. This is the GTIN (Global Trade Item Number), which is created according to the rules of GS1 (to ensure worldwide uniqueness). The JAN number is only a GTIN that is in the number range of GS1 Japan. Technically, therefore, any GTIN can be used. The detailed specification of GS1 (GS1 has the status of a private company and not that of a governmental organisation or anything comparable) can be found at www.gs1.org under the title GS1 General Specifications. The Application Identifiers are described in the GS1 General Specifications in Chapter 3. The description of the code types (abbreviated, based on the ISO standard) and the requirements for print quality can be found in Chapter 5 of the GS1 General Specifications.

In 2015, the "Safety Information for Medicinal Products and Medical Devices No. 323" announced that labelling with the JAN and ITF codes would be phased out. With the JAN code, the EAN/UPC symbology defined in the ISO/IEC 15420 standard is meant in this context (the EAN/UPC code type is referred to as the JAN code if the coded GTIN is in the GS1 Japan number range1). ITF refers to the Interleaved 2 of 5 symbology defined in the ISO/IEC 16390 standard. The code type Interleaved 2 of 5 is referred to as ITF if the GTIN is encoded as the article number in the code and the specifications from Chapter 5 of the GS1 General Specifications are complied with.

 

EAN or JAN code (replaced by GS1 Databar in the variants shown).

Note: the composite part of the code is sometimes referred to as a 2D code. This is only partly true. In fact, it is a stacked code and not a true 2D matrix code. Stacked codes are actually barcodes that, in simple terms, are "cut apart" and printed in lines stacked on top of each other. This made limited sense until around 2010. In the meantime, the availability of highly efficient camera-based scanners has made this disadvantageous for reasons of space and reading efficiency. Therefore, in all other comparable applications, a Data Matrix Code or another true 2D matrix code is used.

Application identifier Meaning Format

01

Article number (GTIN) 14-digit numeric

10

Batch or production lot 1 to 20 digits alphanumeric

17

Expiry date 6-digit numeric, YYMMDD

21

Serial number 1 to 20 digits alphanumeric

30

Quantity 1 to 8 digits, numeric

7003

Expiry date with time 10-digit, numeric, YYMMDDHHMM

Note: The designation of the article number (GTIN) is often equated or used synonymously with the designation of the code type EAN/UPC. This equation is misleading. The code type for which the data encoded in it is synonymous is the EAN/UPC code specified in the ISO/IEC 15420 standard. The article number, in this case the GTIN, can be transported and encoded in different ways and is therefore to be distinguished from the code type.

Code type ITF (replaced by GS1-128)

In the coding of the article number, the packaging level2 is also indicated. The article number is a GTIN. This always comprises 13 digits (numeric, including check digit at the end of the code). The new codes always define a data field with 14 numeric digits (fixed length) for the GTIN. The first digit in this data field is used differently depending on the country and application. The designation for this digit is "Indicator Digit". In the application for medicines in Japan, the Indicator Digit is used as follows:

Medicinal product administered (blister, ampoule, etc.) 0498711111118

Sales packaging 1498711111118

Bundle or variety-pure shipping package 2498711111118

This classification is different from the usual practice. Normally, sales packaging is coded with a leading "0".

 

In principle, this classification applies (according to the latest version of ISO/IEC 15416 from 2016):

ISO class in 1/10 steps ANSI class Meaning
3,5; 3,6; 3,7; 3,8; 3,9; 4,0

A

Very Good
2,5; 2,6, 2,7, 2,8; 2,9; 3,0; 3,1; 3,2; 3,3; 3,4

B

Good
1,5; 1,6, 1,7, 1,8; 1,9; 2,0; 2,1; 2,2; 2,3; 2,4

C

Satisfactory
0,5; 0,6, 0,7, 0,8; 0,9; 1,0; 1,1; 1,2; 1,3; 1,4

D

Sufficient
0,0; 0,1; 0,2; 0,3; 0,4

F

Failed

(Note: The current version of ISO/IEC 15415 only knows the classes 4, 3, 2, 1 and 0. The standard will be revised (year 2021) to introduce the 1/10 evaluation steps).

The range of 0.17mm to 0.41mm is specified as the code size (module size, X-dimension). Recommended is 0.25mm.

Note: Printing these codes with the module size in the range of 0.17mm to 0.25mm with the typical HP-based inkjet printers often integrated in the packaging machines in the pharmaceutical industry is challenging and hardly process-safe at 0.17mm.

 

Print quality and code size

The most commonly used code types (symbologies) are specified by ISO/IEC standards (see above). In the case described here, the application is based on the specifications of the issuing organisation GS1. The GS1 specification use as a basis, among others, the ISO/IEC standards mentioned above. Chapter 5 of the GS1 General Specifications describes the code types as well as the quality requirements.

In 2012, there was a meeting of the associations and the manufacturers on the topic of implementing the coding for Japan. With the invitation from the FPMAJ association, a document was distributed showing the drug categories, various examples of packaging types and coding (https://pdf4pro.com/amp/cdn/24-7-10-5ad6da.pdf).

In addition to the product categories described above, the packaging levels and the labelling requirement, the print quality requirement for the codes was also defined. The requirement is to achieve grade C (satisfactory) according to ISO/IEC 15416. For the composite code, the ISO/IEC 15415 standard is also required. This is not mentioned in the document, but since the composite standard normatively refers to ISO/IEC 15415, it applies as well.

No direct size is mentioned for the GS1-128 in the document. However, it is mentioned that the code should be split into two codes if the width exceeds 100mm. In the example above, this is the case with a module size of 0.29mm (only printable with 600dpi). It can therefore be assumed that nominally the range of 0.17mm to 0.41mm also applies to the GS1-128.
In the document it is pointed out that e.g. with a resolution of 300 dpi the code size cannot be scaled freely.

Only the following is possible:

Size mm
DPI

0,17

0,19

0,21

0,25

0,29

0,32

0,34

0,38

0,42

200 dpi

X

X

300 dpi

X

X

X

X

400 dpi

X

X

X

X

600 dpi

X

X

X

X

X

X

Other resolutions enforce other values.

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Introduction of the "new" coding rules

Press release 337 indicates on page 16 that the introduction will take place from April 2021. According to another piece of information (unfortunately without a source), it seems that in certain cases the implementation will not be required until 2023. In Japan, the topic is being pushed further in order to make product information available to patients and doctors in electronic form, among other things (see https://www.mhlw.go.jp/content/11121000/000682481.pdf).

Conclusion

With the introduction of this coding, similar regulations apply in Japan as in Europe and the USA. While the coding of a serial number (Unique Identifier) for prescription medicines is mandatory in Europe and the USA, in Japan either the batch name or the serial number is mandatory. One challenge is the choice of the GS1 Data- Bar Composite code type. This type of code is more difficult to print in good quality than the Data Matrix code. Furthermore, the space requirement of this code type is significantly higher than that of the Data Matrix Code.

 

The author of this text has found the "Pharmaceutical and Medical Devices Safety Information No. 337" from October 2016 as the latest state of the art. Section 2 refers to the coding regulations (https://www.mhlw.go.jp/file/06-Seisakujouhou-11120000-Iyakushokuhinkyoku/0000185548.pdf and EN: https://www.pmda.go.jp/files/000214756.pdf).

 

About the Author
Wilfried Weigelt (Dipl. Ing. FH)
... has been working as division manager "REA Verifier" at the company REA Elektronik GmbH since 1996.
He has worked on the rules for the coding of medicinal products requiring verification in the German market to protect against counterfeit medicines (securPharm).

Source:
1 GTIN Prefixes: https://www.gs1.org/standards/id-keys/company-prefix
2 Note 298 from the year 2013 - https://www.mhlw.go.jp/www1/kinkyu/iyaku_j/iyaku_j/anzenseijyouhou/298-1.pdf

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