DEPARTMENT OF HEALTH AND HUMAN SERVICES

Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

RE: RESPONSE OF AEGATE LTD.

**Docket No. FDA-2008-N-0120**

*Standards for Standardized Numerical Identifier, Validation, Track and
Trace, and*

*Authentication for Prescription Drugs; Request for Comments*

To Whom It May Concern:

I write on behalf of Aegate Ltd. We are pleased to have this opportunity
to respond to the Request for Comments included in Docket No.
FDA-2008-N-0120, which has been titled "Standards for Standardized
Numerical Identifier, Validation, Track and Trace, and Authentication
for Prescription Drugs; Request for Comments." We are encouraged by and
support expeditious informed action by the FDA in this vital
standards-setting endeavour.

Aegate Ltd. Response

**Introduction**

Aegate provides a unique patient safety network that opens a direct, IT
enabled communications channel between pharmacies and pharmaceutical
companies. The channel attacks counterfeits by allowing for the
verification of the authenticity of the package at the time it is
dispensed, and communicates other important real time information
(expiry, recalls safety) at the same time directly to the pharmacist.

Good real-time communication between the pharmaceutical company and the
pharmacist is becoming essential to ensure patient safety. Aegate
provides a patient safety communications service, which verifies the
identity and authenticity of each individual medicine whilst it is being
dispensed by the pharmacist, and passes on any pertinent safety or
regulatory information before the medicine is handed over to the
patient.

This prevents substandard medicines from being delivered to patients,
such as out-of-date, discontinued, recalled, counterfeit or stolen
medicines. The rapid speed of information delivered by Aegate
(significantly less than one second after scanning) improves existing
product recall methods and ensures that professional pharmacists
maintain their role at the centre of patient care. It also ensures that
the information transfer does not interfere with the pharmacist workflow
and as such does not slow down the pharmacy efficiency.

The Aegate services are currently in operation in Belgium, Greece and
Italy, with plans in place for further growth in the USA and across
Europe in 2008.

Aegate has been trading since 2003 and is backed by PA Consulting Group,
A major worldwide Technology and Consulting firm.

Aegate is pleased to submit the following specific comments to make in
response to the request for information on issues related to standards
for identification, validation, tracking and tracing, and authentication
for prescription drug products.

**A. Standard Numerical Identifier**

**1. Characteristics**

**a. Should the standardized numerical identifier contain recognizable
characteristics (e.g., National Drug Code number) or be random codes?**

Aegate believe that the standard numerical identifier should be a single
string of information constructed from two elements. The first element
should contain the existing National Drug Code (NDC) number, this will
help maintain drug dictionaries, supply chain ordering and replenishment
processes. The second element within the standard numerical identifier
should be a randomised mass serialised identification code. Overall this
will provide for a mechanism to uniquely identify each saleable unit.

Importantly the use of the NDC will ensure that companies do not
inadvertently generate the same unique identifier. The use of the NDC
will reduce the cost and complexity of implementation. This is the
practice in countries that have already legislated for unique numbering
of pharmaceutical packs.

Purely random codes would mean that a standard drug dictionary could not
be used.

**b. Should there be a common header for item/product segregation**

**based on product type: biologic, solid oral dosage form, etc.? If
so,**

**please elaborate.**

Aegate's view is this is not an essential requirement of the code, and
the National Drug Code prefix should be sufficient.

**c. How can parties in the supply chain ensure that the numbers are**

**unique and are not duplicated?**

As stated in point (a) above the number should be made up of two
elements, firstly a product identifier e.g. the National Drug Code and
secondly a randomised mass serialized identification code. Overall this
will provide for a unique number for every saleable unit. The
combination of product identifier (National Drug Code) and a random
number for each pack makes this possible. The use of the NDC will also
ensure that different manufacturers are unable of inadvertently
duplicating the numerical indentifier.

**d. How much value would there be in having the numerical identifier**

**in more than one place for the product (e.g., package and pallet**

**level)?**

The most important place for the unique identifier is on the saleable
unit that is dispensed to the patient, whether 100ml bottle or a pack of
30 tablets.

If required pallets and cases could have unique identifiers, but these
must be different. The use of the National Drug Code would ensure this,
as the code is different for a single pack and an outer.

**e. Should the numerical identifier be machine readable, human**

**readable, or both?**

Ideally both, so that in the event of a technology failure the numerical
identifier could be manually recorded and inserted into the appropriate
database.

**f. Should the numerical identifier include the lot number and/or**

**batch number?**

If printed, read and verified on line then there is an opportunity to
include these details within the numerical identifier. However, in
incorporating this information into the numerical identifier it
considerably increases the complexity of application on the packaging
line.

Where the numerical identifier is printed ahead of time (e.g. where
labels with these codes are specially and securely printed) and is then
applied to the individual dispensing units as they are packed. Then
there is no opportunity to include lot number and expiry date within the
code.

The process should be able to work either with the batch number and lot
identifier within the numerical identifier or where this is held
separately from the numerical identifier.

**2. Standards**

**a. Do standards currently exist for a standardized numerical**

**identifier of prescription drugs?**

Yes, already approved and agreed GS1 standards can be applied to
standardized numerical identifiers. Historically the lack of a common
European Coding Standard across Europe has led to a plethora of
different GS1 standards being used. Regulators in Italy, France, Greece,
Belgium, Spain and Portugal have stipulated different GS1 standards to
be used. The GS1 standard that would best match the requirement above is
a Serialized Global Trade Identification Number (SGTIN)

To solve this problem, the European Pharmaceutical Industry Association
(EFPIA¹) has developed an agreed European Standard to ensure that all
European countries are able to standardize and move to a single coding
position. (1. Reference EFPIA Coding Paper November 2006)

**1. If so, please describe and comment on their application and use.**

Belgium uses a single 1d bar code incorporating the product code and
unique identifier on all pharmaceutical products

In Greece and Italy products have a label with 2 codes (product
identifier and unique number), both are 1d codes

None of these contain lot number or expiry date as they are pre-printed
labels ordered in advance from government printers, (when lot and expiry
is not known) and applied by the manufacturer, or pre-wholesaler before
product enters the distribution chain.

Turkey having considered various coding options has opted to move toward
a mass serialization and authentication model, utilizing both linear and
2D barcodes as the data carrier. (The Turkish Government coding
requirement is in line with the EFPIA Standard quoted under point 2.a
above)

**2. To what extent do these standards reflect stakeholder consensus?**

Aegate are not able to comment on this as our organisation was not
directly involved with their introduction. However, Aegate believes that
in all instances stakeholders were involved in defining which of the GS1
standard should be used in each country and how the process would work.

**3. Comment on whether any of these standards should be the standard**

**adopted by FDA**.

The GS1 SGTIN printed code standard is one option. The EFPIA Coding
Standard is another. For ease of application and integration the SGTIN
would provide for an easier option for manufacturers.

**4. If yes, why? Compare this standard with other standards that**

**exist.**

If looking to incorporate lot number and expiry date then linear code
standards may be too long for some smaller packs.

In this instance other printed code standards such as 2d Datamatrix
should be considered. These are tried, tested and cost effective.

RFID standards also exist, but these have not been agreed upon for the
pharmaceutical industry and have quality, efficacy and privacy concerns.
Routine and widespread use of RFID is untested, costly, complex and
environmentally challenging.

In summary:-

RFID does not represent a "silver bullet" for the identification and
coding of pharmaceutical products, contrary to the assertions of many
tag manufacturers and interested parties it is not the solution to the
industry problems.

A RFID tag is fundamentally just a data carrier, in order to utilize a
data carrier effectively there needs to be agreement on how the data
carrier will be used. This will require the process and procedures
agreed in advance by all supply chain parties.

Currently there is a serious risk that people will believe the hype
around RFID and not stop to consider how a system would operate. This
can result in a very high cost implementation which ultimately is not
fit for purpose. This was one of the primary drivers around the decision
made by The European Federation of Pharmaceutical Industry Associations
(EFPIA) for the use of a cheap 2D coding system to be used in
pharmaceuticals. i.e. should all be driven by requirements and not
technology.

Cost

The cost of RFID tags are expensive in relation to other data carriers.
Depending on complexity of the tag prices range from \$0.30 upwards.
Implementation of equipment and systems to add an RFID tag to a
production line are also significant. RFID tag manufacturers say that
costs will come down as volumes increase (however, this has been said
for the last 5 years). As with any technology dependent product, the
rate of technological change will drive improvements but will also tend
to keep prices high. Any significant cost increase to the pack costs
will have a corresponding negative impact on margins.

Standards

Currently there exist no agreed standards with respect to the use of
RFID with pharmaceutical products. These are being developed by GS1.
Trials have been run with Low Frequency, High Frequency and Ultra High
Frequency tags. Each of these tag types require different reading units
and have very different characteristics. In addition tags can be active
or passive, and read only or read/write compatible. Until standards are
set and agreed in the US, Europe and rest of World there is inherent
risk in the selection of any one of these attributes.(See above)

Accuracy and Effectiveness

As detailed above the different operating frequencies provide for
different physical attributes. This results in different read ranges as
well as different responses to certain materials. It is known that
aluminum foil (blister packs) and liquids interfere with RFID tag
performance. In addition throughput and read rate are sensitive to
volume operation with limitations in collision space and also speed at
which tags can be read.

For the UK and USA pilots Aegate used Passive read only tags at 13.56MHz
with 100% read rate in Pharmacies.

Potential affects of RFID on medicines

Aegate commissioned PA Consulting to carry out a theoretical study on
the potential effects of RFID on medicines. The report was independently
reviewed and agreed by Philips. The conclusions from the study included:

-   A 13.56MHz solution based on the Philips Pagoda provides no
    significant increase in risk to the drugs with reference to the
    current level of background RF radiation from cellphones, microwave
    ovens and other industrial RF sources.

-   Any new RFID system based around UHF technology, built to US
    standards, could increase the field strengths to which the drugs are
    exposed, and could, under certain design circumstances, result in a
    slightly higher level of field than the current background. The
    design of any such UHF system should be reviewed accordingly.

-   No chemical damage to the drugs can be expected as a result of the
    incident RF radiation.

-   The heating of the drugs caused by the RF radiation is
    insignificant.

Aegate understands that the FDA and manufacturers are conducting longer
term stability studies with RFID especially on liquids and biologicals,
with different frequencies and field strengths. However the results of
these studies are not yet published.

Security

It has been proven that certain types of RFID tags can be susceptible to
viruses. This could lead to corruption of tag data and or reading
equipment.

Privacy & Data Protection

Personal privacy is a further concern with RFID tags, the shelf life of
many tags is up to ten years. Given this there is a concern that people
could actively "scan" and identify personal medications in the home
without the permission of the individual in question.

Application and Use

The need to assure patient safety is best achieved by checking that the
product going out the pharmaceutical supply chain is the same as the
product going in. This "good in" equals "good out" principle provides
the simplest, cheapest and most effective way to assure patent safety.
In this environment the drug is dispensed by a pharmacist who has direct
line of sight with the drug, given this there is no advantage to using a
technology solution that does not need line of sight to operate.

Green Credentials

The use of RFID does not promote a "green" approach, the materials and
resources for RFID tags are energy and raw material intensive to
produce.

In Europe RFID meets the definition of electrical and electronic
equipment provided for in the Directives 2002/96/EC on waste electrical
and electronic equipment (WEEE). However if RFID tags are put on the
packaging of the electrical and electronic equipment they are not
covered by the WEEE Directive. If they are put on the equipment, the
producer of the equipment is responsible for recycling.

RFID also has to comply with 2002/95/EC on the restriction of the use of
certain hazardous substances in electrical and electronic equipment \"IT
and telecommunication equipment".

To date there have been few studies comparing the 'carbon footprint' of
an RFID tag versus a printed bar code system implementation. These
analyses are complex in nature and must take into account ancillary
equipment such as readers, printers, IT infrastructure etc as well as
manufacture of consumables such as inks and paper.

**5. If not, is there some aspect that could be changed to make it**

**acceptable as the FDA standard?**

The specification for printed codes should be checked to ensure they
provide for readability at the end of the products shelf life, which
could be 5 years after initial printing.

**6. Has this standard been adopted by other countries?**

GS1 standards are in use world wide on a wide variety of applications
including pharmaceutical products. The EFPIA Coding Standard has been
adopted by Turkey.

**b. Are standards in development or planned for standardized**

**numerical identifiers of prescription drugs in the supply chain? If
so,**

**who is developing these standards and what is the timeline for**

**completion?**

The GS1 organisation is currently developing standards for numerical
identifiers to be used in the prescription drug supply chain.

**c. What are the elements, provisions, and particular considerations**

**that should be included in a standardized numerical identifier of**

**prescription drugs? Please be specific in your response and include**

**examples, where possible.**

As stated previously the numerical identifier should contain at least
two elements. The first a product identifier; which identifies the
licence holder, product name, strength, form and quantity in the pack /
volume. The second a mass serialized number to identify the individual
saleable unit. Both elements combine to provide a unique mass serialised
number for every saleable unit.

Lot number and expiry date information could be included but are not
essential (see earlier comments).

**d. Please comment on implementation of standardized numerical**

**identifiers of prescription drugs in the U.S. supply chain.**

Without the direction of a standardized numerical identifier, the supply
chain players are faced with potential multiple identifiers being
present in the market at one time. This increases complexity, makes
system integration more difficult and adds cost and delay to the
implementation.

In addition to this, the lack of specification of a data carrier means
that manufactures could choose a solution based upon their individual
circumstances. This could lead to further difficulty with the
wholesalers as they will be faced with needing to accept different data
carriers and technologies which may be sub-optimal for their
arrangements. This would have an adverse effect of pushing cost and
complexity down the supply chain to wholesalers and retail pharmacy.
This effect has already been seen in the Californian e.pedigree
legislation where a lack of standard definition resulted in a
proliferation of standards and different data carriers.

The main purpose for using standardised numerical identifiers is patient
safety. The supply chain can be secured by manufacturers applying and
reading these at the start of the supply chain then checking against
this record in a database when dispensed in a pharmacy.

Supply chain efficiency improvements and further increases in patient
safety with e-pedigree can be realised as scanning at other stages in
the supply chain are introduced including meeting e-pedigree
requirements.

Focussing on authentication at the point of dispensing enables a faster
implementation and roll out that will provide a significant step change
in securing patient safety in a cost effective manner.

In US pharmacies there is much more dispensing from 'bulk' whether a
large pack supplied from a manufacturer or the use of hoppers which are
filled from large bulk containers. Any implementation of standardized
numerical identifiers must consider this dispensing from bulk, as this
represents a weakness in the overall supply chain security and overall
patient safety. Most western markets are increasingly moving to original
pack dispensing which carries less risk of error and fraud than
dispensing from bulk.

**e. Please comment on any technical or information technology**

**concerns related to a standardized numerical identifier.**

None relating to the identifier itself. There are concerns relating to
the technology used to apply, carry and read the identifier (data
carrier). The choice of data carrier must be selected in such a way that
the technology must be proven, cost effective with a very high correct
read rate, easy and quick to scan and non destructive. The data carrier
should not to affect the medicine in any way and be able to be used in
all pharmacy and dispensing locations. In addition the technology should
not infringe any public privacy laws, nor should it adversely impact the
environment. Either from its use of scare raw materials, energy
consumption in manufacture or from its environmental impact upon
disposal.

**f. Comment on any \`\`lessons learned\'\' from foreign experience
with**

**standardized numerical identifiers**.

The Aegate experience is that patient safety can be improved using a
simple 1d linear bar code with combined elements of a product identifier
and a unique number. The Aegate solution is standard independent and can
work with any applied standard, this is important as different countries
will select and legislate for different standards. It is also critical
in the adoption of standards to give industry sufficient time for their
effective introduction.

**3. Economic Impact**

**a. What are the usual practices and associated costs that now exist**

**for applying bar codes and other technologies for standardized**

**numerical identifiers on packages and pallets?**

Costs for applying barcodes are widely known, it is recognised that
barcode technology represents the cheapest and most effective way of
identifying products for movement through the supply chain. Although in
other markets manufacturers have to buy the labels with the standardized
numerical identifiers pre-printed from the government in Italy. In
Greece and Belgium they are supplied by the government. Costs for other
data carrier technologies like RFID are also know and are considerably
more expensive than barcodes, both to install and apply. Consideration
needs to be given to the additional cost of goods that any data carrier
would create. In considering the pharmaceutical supply chain the role of
low-cost generic manufacturers needs to be understood.

**b. What are the associated costs for the application, use, and**

**maintenance of standardized numerical identifiers?**

Not known in detail, however membership of GS1is required to be able to
use their standards. This registration is important to ensure no
duplicate product codes or formats are used.

**c. What are the associated costs or processes for updating the**

**standards as needed?**

Not known by Aegate

**d. What are the benefits of using standardized numerical**

**identifiers?**

The same identifier reading technology can be used throughout the supply
chain for all products. These identifiers providing they are also unique
to each saleable unit can be used to improve patient safety and reduce
the risk of counterfeit goods from entering the legitimate supply chain.

**4. Harmonization With Other Countries**

**a. What standards or unique identification systems do other**

**countries have in place, currently under development, or planned for**

**the future? If they are under development, please include a timeline**

**for completion.**

Belgium uses a GS1 standard single 1d bar code incorporating the product
code and unique identifier on all pharmaceutical products

In Greece and Italy products have a label with each GS1, 2 codes
(product identifier and unique number), both are 1d codes

None of these contain lot number or expiry date as they are pre-printed
labels ordered in advance from government printers, (when lot and expiry
is not known) and applied by the manufacturer, or pre-wholesaler before
product enters the distribution chain.

Turkey having considered various coding options has opted to move toward
a mass serialization and authentication model, utilizing both liner and
2D barcodes as the data carrier.

The European Pharmaceutical Industry Association (EFPIA¹) has developed
an agreed European Standard to ensure that all European countries are
able to standardize and move to a single coding position. (1. Reference
EFPIA Coding Paper November 2006)

**b. Comment on any \`\`lessons learned\'\' from foreign experience
with**

**standardized numerical identifiers**.

They generally work well, having different standards, requirements and
legislation in each country is not an issue. Using printed codes it is
important to ensure that the standard of printing is maintained to
ensure the code can be read many months or years later. The GS1
standards used stipulate printing requirements including degree of
blackness and sharpness. With printed technologies one solution is to
monitor the quality and readability on each code printed. However, what
is important in the use of standardized numerical identifiers is the way
the identifier is used within the supply chain and the selection of the
numerical identifier should be fit for purpose.

**B. Standards for Validation**

Aegate has no comment to make on standards for validation of
prescription drugs

**1. Do standards currently exist for validation of prescription
drugs?**

**a. If so, please describe and comment on their application and use.**

**b. To what extent do these standards reflect stakeholder consensus?**

**c. Comment on whether any of these standards should be the standard**

**adopted by FDA.**

**d. If yes, why? Compare this standard with other standards that**

**exist.**

**e. If not, is there some aspect that could be changed to make it**

**acceptable as the FDA standard?**

**f. Has this standard been adopted by other countries?**

**2. Are standards in development or planned for validation of**

**prescription drugs in the supply chain?**

**If so, who is developing these standards and what is the timeline**

**for completion?**

**3. What are the elements, provisions, and particular considerations**

**that should be included in a validation standard for prescription**

**drugs? Please be specific in your response and include examples,
where**

**possible.**

**4. Please comment on implementation of validation of prescription
drugs**

**in the U.S. supply chain.**

**5. Please comment on any technical or information technology
concerns**

**related to validation.**

**6. Comment on any \`\`lessons learned\'\' from foreign experience
with**

**validation.**

**C. Standards for Track and Trace**

**1. Do standards currently exist for track and trace of products in
the**

**supply chain, generally?**

Aegate is not aware of any track and trace standards

**a. If so, please describe and comment on their application and use.**

N/A

**b. To what extent do these standards reflect stakeholder consensus?**

N/A

**c. Comment on whether any of these standards should be the standard**

**adopted by FDA.**

N/A

**d. If yes, why? Compare this standard with other standards that**

**exist.**

N/A

**e. If not, is there some aspect that could be changed to make it**

**acceptable as the FDA standard?**

N/A

**f. Has this standard been adopted by other countries?**

N/A

**g. If standards are under development or planned for the future,**

**please include a timeline for completion.**

N/A

**2. Do standards currently exist for track and trace of prescription**

**drug products in the supply chain?**

Aegate is not aware of any track and trace standards

**a. If so, please describe and comment on their application and use.**

N/A

**b. To what extent do these standards reflect stakeholders**

**consensus?**

N/A

**c. Comment on whether any of these standards should be the standard**

**adopted by FDA.**

N/A

**d. If yes, why? Compare this standard with other standards that**

**exist.**

N/A

**e. If not, is there some aspect that could be changed to make it**

**acceptable as the FDA standard?**

N/A

**f. Has this standard been adopted by other countries?**

N/A

**3. Are standards in development for track and trace of prescription**

**drugs in the supply chain?**

Aegate is not aware of any track and trace standards in development

**If so, who is developing these standards and what is the timeline**

**for completion?**

N/A

**4. What are the elements, provisions, and particular considerations**

**that should be included in a track and trace standard for
prescription**

**drugs? Please be specific in your response and include examples,
where**

**possible.**

There are three key considerations:

1\) Scope to cover from manufacturer to point of dispensing to patient
in a pharmacy.

Minimum standard: track and trace at manufacturer and pharmacy only. The
standard should allow for track and trace to grow as other parts in the
distribution chain read the codes and enter that information into track
and trace data base.

The standard should consider what can be achieved now to immediately
benefit patients and stakeholders as well as define the steps to a full
trace system. For example allow case level pedigree with pedigree
inference for individual packs.

2\) Standard should include aspects of data privacy, access and
management. Who can see the track and trace information and for what
purpose needs to be defined.

3\) Standard should make it easy for all stakeholders to participate,
with agreement from all

**5. Please comment on implementation of track and trace for
prescription**

**drugs in the U.S. supply chain, including, but not limited to,**

**feasibility, costs, timeline, interoperability, information
technology,**

**and data storage.**

Given the number of manufactures, wholesalers and distributors
implementation of a full track and trace system in one go is a big step
which has not been successfully implemented anywhere.

It is important to ensure that all parties fully understand the data
volume that will be required to be exchanged at each point. The table
below details the number of data transactions that are required to
support an e.pedigree solution in California alone. This figure should
be increased by a factor of 80 to cover the entire US market.

![](media/image1.wmf){width="6.000694444444444in"
height="1.5694444444444444in"}![](media/image2.wmf){width="5.997916666666667in"
height="1.3666666666666667in"}

It is critical to ensure the e.pedigree transfer can be achieved with no
delay or loss of operating efficiency through the supply chain. This is
especially critical for wholesalers who rely on rapid throughput, have
to deal with the complexity of selling a very high percentage of
individual saleable units and have very low operating margins. If the
wholesalers had to scan every saleable unit in and out to identify and
generate the e.pedigree this would add 103,000 days to the processing
time for all wholesalers over a year just for California alone (assuming
each scan takes 5 seconds).

Whilst track and trace requirements detail the data required to support
the pedigree, the only requirement to identify suspect drugs is through
the use of inspectors asking for pedigree records at spot checks
throughout the supply chain.

If an individual or organization wishes to bring illegal drugs into the
supply chain, they would also have the capability to provide a "false"
pedigree to support the shipment.

Given the points above regarding the lack of standardization, it would
be extremely difficult to identify "rogue" drugs. Unfortunately, the
most likely place where these drugs will be identified will be in the
market place when patients have had an adverse event.

In order to remove this risk, the system needs to be able to identify
whether a drug does come from a reputable manufacturer. In Europe, this
area is being addressed by the pharmaceutical industry association
(EFPIA) promoting the use of an authentication system to identify
suspect drugs at the point they are dispensed.

**6. Discuss how the data generated from track and trace should be
held,**

**where it should be held, concerns related to data security, and
means**

**for access to ensure interoperability for data sharing. What
elements**

**should be included in such a standard for data exchange, storage,
and**

**interoperability?**

Ownership of the data needs to be agreed, as do rights of access.
Currently there is money flow associated with sale of distribution chain
information. If this money flow is altered as a result of track and
trace then it will be difficult to implement. Implementation plans need
to recognise the need to maintain existing dataflow and charging
mechanisms.

**7. Comment on any \`\`lessons learned\'\' from foreign experience
with**

**track and trace.**

In Italy the Government introduced the Bollini system (January 2005) to
provide for a full track and trace system at each stage in the
pharmaceutical supply chain. Unfortunately this system has never been
fully operational due to the technical difficulties and an
underestimation of the data volume to be transferred at each stage.

**D. Standards for Authentication**

**1. Do standards currently exist for authentication of products in
the**

**supply chain, generally?**

The EFPIA coding standard was developed specifically to enable
pharmaceutical products to be authenticated at the point of dispense.

**a. If so, please describe and comment on the application and use.**

Standards exist and are applied for coding of pharmaceuticals. Other
standards can be applied for data security and transfer, software
development etc.

**b. To what extent do these standards reflect stakeholders**

**consensus?**

The EFPIA coding standard was agreed by the European Pharmaceutical
Industry and associated stakeholders.

**c. Comment on whether any of these standards should be the standard**

**adopted by FDA.**

The EFPIA Coding Standard would be suitable for use by the FDA.

**d. If yes, why? Compare this standard with other standards that**

**exist.**

The coding standard was developed specifically to meet the needs of the
pharmaceutical industry. However, it varies from a SGTIN in the fact
that it contains the lot and expiry information.

**e. If not, is there some aspect that could be changed to make it**

**acceptable as the FDA standard?**

If you were to remove the lot and expiry dating from the EFPIA code this
would make adoption easier from smaller pharmaceutical companies and
generic manufactures due to the reduced complexity.

**f. Has this standard been adopted by other countries?**

The EFPIA standard has been adopted by Turkey (8^th^ largest
pharmaceutical market in the World)

**2. Do standards currently exist for authentication of prescription
drug**

**products in the supply chain?**

Aegate is the only organisation currently active in the Authentication
of prescription drugs in the supply chain. As such Aegate could be
considered the standard.

**a. If so, please describe and comment on the application and use.**

The Aegate system holds in secure database information supplied by
pharmaceutical manufacturers relating to the unique identification of
every saleable unit. This database is accessed every time a pharmacist
dispenses a medicine. The Aegate system provides a patient safety
communications service which verifies the identity and authenticity of
each individual medicine whilst it is being dispensed by the pharmacist,
and passes on any pertinent safety or regulatory information before the
medicine is handed over to the patient.

**b. To what extent do these standards reflect stakeholders**

**consensus?**

The Aegate system is endorsed by local pharmacy associations and
pharmaceutical manufacturers.

**c. Comment on whether any of these standards should be the**

**numerical identifier standard adopted by FDA.**

Authentication at the point of dispense should be adopted by the FDA to
improve patient safety.

**d. If yes, why? Compare this standard with other standards that**

**exist.**

Authentication is far more effective at stopping suspect product
(counterfeit, stolen, short expired or recalled) than an e.pedigree or a
pure track and trace solution. This is because every saleable unit is
checked at the point of dispense. This action not only identifies
counterfeit medicines it will provide for other important patient safety
information to be carried at the same time.

**e. If not, is there some aspect that could be changed to make it**

**acceptable as the FDA standard?**

N/A

**f. Has this standard been adopted by other countries?**

Authentication has been adopted in Belgium, Greece, and Italy.

**3. Are standards in development for authentication of prescription**

**drugs in the supply chain?**

Aegate is not aware of any such general standard in development.

**If so, who is developing these standards and what is the timeline**

**for completion?**

N/A

**4. What are the elements, provisions, and particular considerations**

**that should be included in an authentication standard for
prescription**

**drugs? Please be as specific as possible and include examples, where**

**possible.**

**The Authentication Approach**

In the presentation made by Aegate to the California Board of Pharmacy
on December 5^th^, the proposal was considered to build on the
e.pedigree requirements by introducing an authentication system.

In working through this example, it was identified that the
authentication approach could also simplify the need to identify the
pedigree to saleable unit at each change in ownership, by running an
e.pedigree at case level.

This approach is made possible since the authentication process
identifies any suspect drug. The supplier could subsequently be
determined by investigation of the case pedigree.

Under this approach, the authentication process would be a supplementary
activity, if the pedigree was maintained at the saleable unit pedigree
level, but would be a required element if the decision was made to
create a case level e.pedigree only.

*The Authentication Solution*

Manufacturers add a agreed standard barcode or Radio Frequency
Identification (RFID) tag with a random unique serialized number which
identifies each and every individual pack of pharmaceutical drugs.

The pharmaceutical manufacturer sends the unique serialized codes, and
other safety or security information, to the authentication provider
when their pharmaceutical drugs are released into the supply chain.

The information is electronically stored and maintained by the
authentication provider(s) in a secure database located in the US.

In pharmacies, the barcode on the pack is scanned and electronically
authenticated against the information held in the secure database.

Results of authentication are passed back in less than a second to the
pharmacist.

Counterfeit, recalled, stolen, illegal or out-of-date drugs are
identified and appropriate safety warnings or notices (e.g. recent
announcement of adverse events) are provided to the pharmacist as part
of the authentication service.

![](media/image3.wmf){width="7.384027777777778in"
height="2.91875in"}Diagram of authentication process

**Authentication Benefits**

Authentication enables critical operations, such as the identification
of counterfeit and stolen medicines, out-of-date notification, drug
recalls and communication of safety messages, to be managed more
effectively and brings an additional safeguard to patients and
pharmacists.

Authentication creates a direct, two-way communications network between
the pharmaceutical manufacturer and multiple points of dispensing which
provides instant, real time authentication, and relevant drug safety
information about the individual pack dispensed.

Authentication takes place at the point of dispensing where the
pharmacist has line of sight of the drug. This increases patient safety
at the final point in the supply chain.

Authentication complements existing anti-counterfeiting and security
measures, e.g. tamper evidence, providing an extra layer of patient
protection.

This authentication technology is very similar to that used for credit
card authentication, but works at a much faster speed (typically 300
milliseconds).

*Flexibility of Operation*

An authentication system can work with printed barcodes (1- or
2-dimensional), as well as more sophisticated technologies such as Radio
Frequency Identification (RFID).

The authentication system is integrated with dispensing point (pharmacy)
software to minimize the impact on pharmacy workflow.

There are no constraints on the number of dispensing points.

*Regulatory Considerations*

The authentication database holds no patient or prescriber information.
Information relating to the unique serialized codes remains the property
of the pharmaceutical manufacturer and, similarly, the information
relating to the dispensed pharmaceutical drug remains the property of
the pharmacist.

The authentication provider complies with national and international
regulations relating to data storage, ownership and transfer across
country borders.

*Simpler Installation (as only the manufacturer and dispensing point are
required)*

The authentication solution works most effectively when it is fully
integrated into pharmacy software systems so that pharmacists gain
access through their existing software package.

Depending on the unique serialization technology used (e.g. linear
barcodes), the solution provider can make use of standard scanners in
the pharmacy. However, it is likely that scanners at the point of
dispensing would need to be upgraded to read either a 2D barcode or a
RFID tag.

The authentication solution has been developed around the pharmacist so
that authentication enhances the dispensing process, rather than hinders
it.

**Inference**

This report recommends that the principle of inference be used within
the supply chain to simplify workload and activity. However, this needs
to occur without compromise to the overall principles of the current
legislation, retaining the need for a pedigree.

The use of authentication to secure the supply chain is key to enabling
a decision to be made on the adoption and use of inference within the
supply chain.

Authentication secures each saleable unit at the point of dispense and,
by doing this, it will allow the level of control and detail in the rest
of the supply chain to be reduced.

The use of e.pedigree at a case level would significantly reduce the
number of e.pedigree's required and thus simplify reporting.

Inference is currently used within the pharmaceutical supply chain and,
as such, it will still enable the authorities to track back using the
case e.pedigree to establish criminal intent.

**A review of stakeholder requirements in the positioning and use of
Authentication within the supply chain.**

*Manufacturers*

Authentication is currently used where legislation requires the use of a
unique identification number to be applied to the sales pack. This
facilitates the implementation of an authentication system.

In completing this activity, the manufacturer can chose between RFID and
or barcode identifier. Since the authentication system can work with
either data carrier. However, if authentication at the point of dispense
is going to be used, then this activity can be more cheaply supported
with the application of a barcode label.

The adoption of the principle of inference will allow for the
manufacturer to generate the e.pedigree at a higher level, reducing the
both the level of detail of the e.pedigree and the number of e.pedigree
records required.

*Wholesalers*

The requirement for an e.pedigree down to each saleable unit will place
extreme pressure on wholesalers to both identify each saleable unit and
produce the e.pedigree. This task will be further complicated by the use
of different approaches by manufacturers in both the use of data carrier
and the coding standards used.

The adoption of an authentication process eases this since it would
allow the principle of inference to be used throughout the supply chain.
This would benefit the wholesaler since it would remove the need to
generate an e.pedigree at the saleable unit level. Therefore, the bulk
of shipments could be made to retail pharmacy without the need to
generate and send an e.pedigree. (Full case shipments would require an
e.pedigree)

*Pharmacists*

Pharmacists will also experience extreme pressure following the
requirement for an e.pedigree down to the saleable unit. Under the new
legislation, each pharmacy will be responsible to check that an
e.pedigree has been presented for all drugs delivered from a wholesaler.
These pedigrees will need to be made available as and when requested by
inspectors.

The adoption of an authentication system which would allow inference
would be of significant benefit to the pharmacy. Not only would the
pharmacist be able to use authentication as an instant check to verify
drugs before they are dispensed, but the receipt of the e.pedigree would
be simplified.

*Patients*

The use of authentication would have a significant advantage for patient
safety. The ability to authenticate prior to the dispensing process
would enable the pharmacist to check for counterfeit goods, as well as
for expired or recalled drugs. Therefore, with authentication, it would
be less likely that any suspect drugs would be dispensed.

*Government and Regulatory*

The use of authentication would have advantages for the government and
regulatory organizations as the supply chain would be secured and the
case level e.pedigree would be able to identify criminal intent. In
addition, the reduced complexity of the e.pedigree would have a positive
advantage to everyone in the supply chain. This would help to ensure
that drug prices did not escalate because of increased handling and
processing costs within the supply chain.

**5. Please comment on implementation of authentication for
prescription**

**drugs in the U.S. supply chain, including, but not limited to,**

**feasibility, costs, timeline, interoperability, information
technology,**

**and data storage.**

Aegate are intending to run an Authentication pilot in California to
identify and understand these points.

**6. Comment on any \`\`lessons learned\'\' from foreign experience
with**

**authentication.**

It works, can be integrated seamlessly into pharmacy operations with
zero impact on dispensary work flow.

Data ownership is key, needs to be 'owned' by pharmacist who scans the
product

Service is appreciated and valued by pharmacies. and offers a unique
patient safety messaging service

Offers pharmaceutical companies brand protection and patient safety
messaging opportunity

**E. Prioritization**

**Please comment on the priority for development and implementation of**

**identification, validation, authentication, and tracking and tracing**

**standards.**

**1. Should certain standards be developed and implemented before**

**others?**

Agreement on coding standards to use and inference is important.

Commitment to Authentication.

**2. Should certain standards be developed and implemented**

**concurrently?**

**III. Comments**

N/A

Thank you for your attention to these matters, and for your willingness
to hear our input. We look forward to continuing to work together to
secure the nation's drug supply. Please feel free to contact Aegate Ltd.
at any time if we can be of assistance.

The best route for contact is via:-

Graham Smith , Graham.Smith@aegate.com

VP Business Development

Yours truly,

Graham Smith,

VP Business Development

Aegate Ltd.

123 Buckingham Palace Road,

London, SW1W 9SR

United Kingdom.