Automated Dose Dispensing (ADD)
Guidelines:
Best Practice for the ADD Process,and Care and Safety of Patients
Deadline for comments: 24 February 2017
Comments should be sent to ADD@edqm.eu

The purpose of these guidelines is to harmonise the standards and approaches to automated dose
dispensing across Europe and to help ensure that this service is provided to a consistently high standard
which ensures the safe supply of medicines to patients.
• EDQM’s work on this topic began with the identification of a need for guidance by theCommittee of Experts on Quality and Safety Standards in Pharmaceutical Practices andPharmaceutical Care (CD-P-PH/PC) in 2012.
• The document was then drafted by a Working Party of Experts in Automated Dose Dispensing.
• A workshop with stakeholders, interested parties and authorities took place in September 2015.
• This DRAFT guideline document was finalised by CD-P-PH/PC in summer 2016 and released by
the Steering Committee, the European Committee on Pharmaceuticals and Pharmaceutical Care
(CD-P-PH) at its meeting in September 2016.

Version dated:
26 September 2016

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Automated Dose Dispensing (ADD) Guidelines:
Best Practice for the ADD Process,and Care and Safety of Patients

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TABLE OF CONTENTS

89SUMMARY
PREFACE
1. SCOPE
2. DEFINITIONS
3. SETTING AND LEGAL FRAMEWORK

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PART ONE: AUTOMATED DOSE DISPENSING: STANDARDS PERTAINING TO THE ADD SITE AND OPERATIONS
4. PERSONNEL AND TRAINING
5. PREMISES AND EQUIPMENT
6. PRESCRIPTIONS
7. MEDICINAL PRODUCTS: TRACEABILITY, SUITABILITY AND STABILITY
8. AUTOMATED DOSE DISPENSING PROCESS
9. DELIVERY (DISTRIBUTION) AND S UPPLY TO PATIENTS
10. WASTE MANAGEMENT
11. QUALITY ASSURANCE
12. DOCUMENTATION, POLICIES, PROCEDURES AND DOCUMENT RETENTION

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PART TWO: PATIENT CARE ACTIVITIES ASSOCIATED WITH THE AUTOMATED DOSE DISPENSING PROCESS
13. LEGAL BASIS
14. ADD PRESCRIPTION/ORDER AND RESPONSIBILITY FOR PATIENT CARE
15. PATIENT SUITABILITY
16. PATIENT CONSENT
17. REVIEW OF PATIENT’S MEDICATION THERAPY, PATIENT INFORMATION AND COUNSELLING
18. DOCUMENTATION AND RECORDS

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REFERENCES

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Summary
The purpose of these guidelines is to harmonise the standards and approaches to automated dose
dispensing across Europe, to help ensure that this service is provided to a consistently high standard which
ensures the safe supply of medicines to patients. These guidelines should be utilised by all pharmacies andmanufacturers involved in automated dose dispensing, as well as by national authorities in countries where
this service is provided.

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Automated dose dispensing (ADD) is the dispensing, performed by a method involving an automatedprocess, of one or more different medicinal products into an ADD container or pouch for a patient to takeat a particular date and time. This approach is used to address the increase of polypharmacy, common for
elderly patients. ADD is carried out in various settings across Europe, for example in licensed
manufacturers or companies and large and small scale hospital and community pharmacies. Regardlessof the scale of production, or the setting in which the ADD site operates, the quality management system
must ensure that the quality, safety and efficacy of the medication dispensed into an ADD container ismaintained.

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In Europe, the medicinal products legislation focuses on three main domains: manufacturers, distributors(wholesalers) and pharmacies. ADD does not fit entirely into the core activity of any of these domains but
elements of ADD overlap with each domain. There is no common set of criteria or standards available toguide regulators, providers and patients about how ADD should be carried out, and therefore there are
significant disparities in the way in which ADD is deployed and in how it is regulated in different countries.

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These guidelines address the issues to be considered when setting up an ADD site, the standards that should
be applied to the ADD process and the associated care of the patient. Part One details standards pertaining
to the ADD site and operations. This includes requirements for the premises and equipment, training of
personnel and the need to have a responsible pharmacist at the ADD site overseeing the management of allactivities relating to the pharmaceutical process. Part Two details standards for patient care activities
associated with the ADD process. This includes the need to carry out a suitability assessment for all patientsprior to supplying medicines via ADD, along with regular reassessments and reviews of their medication, toensure that it is adding value to the patient’s care. The advantages of ADD for an individual patient should
always outweigh any potential risks and be decided on a case-by-case basis.

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These guidelines should be read in conjunction with any national regulations, standards or guidance that
apply in the country where the ADD site is situated, for example regarding labelling and record keeping ofdispensed medicines, requirements for disposal of waste medicines and responsibility for patient care
activities. If an ADD site is a licensed manufacturer or distributor, Good Manufacturing Practice (GMP) andGood Distribution Practice (GDP), must also be adhered to.

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Disparities between national regulations and between statuses of ADD sites should lead national
authorities to consider establishing a legal framework for ADD, as well as standards or guidance. Thisshould facilitate compliance with relevant legislation based on the principles of GMP and GDP and theseguidelines. It is essential to assess whether, and how, to set standards for the deployment and operation of
ADD sites, so that these standards can be monitored and can drive quality improvement in a clear andconsistent way.

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The Automated Dose Dispensing Guidelines have been developed by a working group of experts fromindustry, academia, and government from across Europe and discussed, reviewed and approved by theCommittee on Quality and Safety Standards in Pharmaceutical Practices and Pharmaceutical Carecoordinated by the European Directorate for the Quality of Medicines and Healthcare (EDQM – Council ofEurope).

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PREFACE:86

Automated Dose Dispensing (ADD) was originally developed as a tool to enable unit dose provision,
especially in institutional settings, and as a technical aid to free up resources for patient care1. Bar codetechnology has extended the application and use of ADD systems. The use of ADD to supply the needs ofpatients in certain institutional settings is frequent across Northern Europe 2-4. ADD is also supplied topatients in ambulatory care. In the USA various forms of ADD have also been adapted to provide added
security in the supply of certain types of medicinal products/preparations and to manage stock more
efficiently in large healthcare establishments, within many different specialist units5-6. ADD has been
associated with reduced distribution costs, fewer errors and better medication adherence. A recent study
in the Netherlands 21 showed improved adherence in older patients receiving their medication via ADD.

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However, the widespread uptake of ADD has led to concerns about the maintenance of the integrity of the
preparations, errors during the processes, 1,7 as well as the impact of ADD on the behaviour and attitudes of
the carers and patients 8,9. Dispensing of original packages by automated methods poses few problems,
provided the packaging meets Good Manufacturing Practice (GMP) standards. However, the re-packaging
and re-labelling of individual units of medicinal products requires the opening of secondary packaging andthe removal of primary packaging, which poses risks for quality and integrity, and quality defects and errors
have been found 10-11. Little work has been published on the stability of medicinal products re-packed indifferent types of compliance aids, and criteria for the suitability of their use in ADD have not been
established and validated 12-13. Medication errors and discrepancies have been shown to be decreased
under some circumstances 9, 14 and increased in others 16-17. However, ADD may also lead to continuation of
supply of medicinal products that are no longer needed 17-18, may influence the frequency with whichchanges are made to prescriptions and to the regularity with which medication reviews are requested andconducted 19-20 and may reduce medication knowledge when compared to manually dispensed drugs21.

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Furthermore, the benefits claimed for the use of ADD have not been extensively investigated and theevidence that has been published is not complete and not substantial 22-23. Questions about technical,
managerial, regulatory and clinical issues have been addressed to some extent in guidelines and regulations
but not at a comprehensive level 24-29, and no overall framework of guidance for policy-making isavailable30.

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Therefore, the use of ADD should be carefully considered with respect to the types of medicinal products
involved, the type of patient and their clinical needs, and the care setting and type o f supportive carethat is available. Labelling is an integral element of a dispensed medicinal product, as advice on the use of a
medicinal product for patients and healthcare professionals is essential to ensure safety, quality andefficacy in use. The advantages of ADD for an individual patient should outweigh the disadvantages oflosing the original labelling. It is essential to assess whether, and how, to set standards for the
deployment and operation of ADD sites, so that these standards can be monitored and can drive quality
improvement in a clear and consistent way.

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To date, policies and operational procedures have been developed and evaluations of the technical andhealth service impact of ADD have been carried out in countries using ADD. The significant disparities in theway in which ADD is deployed and in how it is regulated means that there is no common set of criteria or

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standards available to guide regulators, providers and patients.

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1. SCOPE:

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The Council of Europe Committee of Experts on Quality and Safety Standards in Pharmaceutical Practices
and Pharmaceutical Care (CD-P-PH/PC), supervised by the superior body of the European Committee on
Pharmaceuticals and Pharmaceutical Care (CD-P-PH), decided to develop guidelines on automated dose
dispensing (ADD).

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The CD-P-PH/PC decided that the guidelines would address both the ADD process and the associated careof patients, but would not address manual dose dispensing. The guidelines focus on the areas of greatest
patient risk. Following on from a survey review of the different systems in place in different countries in
Europe, the guidelines aim to harmonise the standards for ADD. The guidelines address the issues thatshould be considered and the standards that should apply to the ADD process, and the associated care ofpatients. The topics to be addressed in the guidelines were decided by the CD-P-PH/PC. The guidelines
have been drafted by an ADD working party set up by the Committee of Experts CD-P-PH/PC, thensubmitted for approval of the scientific and technical contents by the Committee of Experts CD-P-PH/PC,
and finally submitted for adoption by the CD-P-PH, Steering Body.

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2. DEFINITIONS:

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Automated Dose Dispensing (ADD): Automated dose dispensing is the dispensing, performed by a method
involving an automated process, of one or more different medicinal products into an ADD container/pouch.
One container/pouch contains either one, some or all units of medicine an individual patient needs to takeat a particular date and time. The medicinal products may be removed from their (original) primarycontainers before they are dispensed via ADD; if the primary packaging container is a blister, this process iscalled “deblistering”. Alternatively, medicinal products may be dispensed into the ADD containers/pouches
in their primary packaging.

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Unit Dose Dispensing (excluded from the scope of this guideline): a method by which individual doses of
medicinal products are repackaged into individually labelled containers/pouches, e.g. in a hospital setting.
This method does not involve individual patient dispensing.

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Manual Dose Dispensing (excluded from the scope of this guideline): where the dispensing of medicinal
products into individualised patient medication doses occurs manually (without the use of automatedsystems).

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The World Health Organization1 defines the manufacturer, manufacture and production as follows:
Manufacturer: A company that carries out operations such as production, packaging, repackaging, labelling
and relabelling of pharmaceuticals.

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WHO good manufacturing practices for pharmaceutical products: main principles, Annex 2, WHO Technical Report
Series, 986, 2014,; www.who.int/medicines/areas/quality_safety/quality_assurance/TRS986annex2.pdf?ua=1.

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Manufacture: All operations of purchase of materials and products, production, quality control, release,storage and distribution of medicinal products, and the related controls.
Production: All operations involved in the preparation of a pharmaceutical product, from receipt ofmaterials, through processing, packaging and repackaging, labelling and relabelling, to completion of thefinished product.

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Good Manufacturing Practice (GMP): The principles of Good Manufacturing Practice are stated in Directive
2003/94/EC. Within the European Union, GMP is defined as:‘Good manufacturing practice’ means the part of quality assurance which ensures that products are
consistently produced and controlled in accordance with the quality standards appropriate to theirintended use’2.

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The WHO defines GMP as: ‘Good manufacturing practice (GMP) is a system for ensuring that products are
consistently produced and controlled according to quality standards. It is designed to minimise the risks
involved in any pharmaceutical production that cannot be eliminated through testing the final product. The
main risks are: unexpected contamination of products, causing damage to health or even death; incorrectlabels on containers, which could mean that patients receive the wrong medicine; insufficient or too much
active ingredient, resulting in ineffective treatment or adverse effects. GMP covers all aspects of production
from the starting materials, premises and equipment to the training and personal hygiene of staff. Detailed,written procedures are essential for each process that could affect the quality of the finished product.
There must be systems to provide documented proof that correct procedures are consistently followed ateach step in the manufacturing process - every time a product is made3’.

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Good Distribution Practice (GDP): The principles of Good Distribution Practice are stated in the EU
guideline 2013/C 343/01 implementing Directive 2001/83/EC. The European Medicines Agency describes
the concept of Good Distribution Practice as:‘Good distribution practice (GDP) ensures that the level of quality determined by GMP is maintained
throughout the distribution network, so that authorised medicinal products are distributed to retailpharmacists and others selling medicinal products to the general public without any alteration of theirproperties’4.

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3. SETTING AND LEGAL FRAMEWORK:

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A. Background: The medicinal products legislation in Europe focuses on three main domains:
manufacturers, distributors (wholesalers) and pharmacies. ADD does not fit entirely into the core activity of
any of these domains but elements of ADD overlap with each domain. Applying detailed patient information
to a medicinal product and breaking units from manufacturer’s original packaging traditionally occurs, inmany countries, within community and hospital pharmacy settings. In other countries, pharmacies are
required to supply original medicinal product packages to patients. The packaging/repackaging of

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Directive 2003/94/EC (Article 2, Definitions, no. 6).
www.who.int/medicines/areas/quality_safety/quality_assurance/gmp/en/
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www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000154.jsp
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medicinal products traditionally occurs in a pharmaceutical company, carried out by a pharmaceutical(licensed) manufacturer operating in accordance with GMP. GDP is also applicable where external supply
occurs for distribution of medicinal products.
B. Legal Framework: National authorities should consider establishing a legal framework for ADD, whichsets out the minimum standards that an ADD site must adhere to. It is recommended that national
authorities establish guidelines or standards to facilitate compliance with relevant legislation based on
the principles of GMP and GDP and these guidelines.

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C. Setting: In different countries in Europe, ADD practices occur in different settings and in some countries
these practices occur in more than one setting. These settings are:
1. Community or hospital pharmacies supplying medicinal products to their own patients. In thiscircumstance the entire process, i.e. review of patients’ medication, dispensing and supply of
medication and any associated counselling occur at the one site.
2. Community pharmacies supplying medicinal products to other pharmacies or healthcare
institutions. In this circumstance dispensing is carried out by the ADD pharmacy, and professional
control is usually the responsibility of the dispensing pharmacy or divided between the ADD siteand dispensing pharmacies.
3. Pharmaceutical manufacturers or other companies supplying medicinal products to pharmacies ordirectly to patients on behalf of the pharmacies. In this circumstance professional control is usually
the responsibility of the pharmacy.

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At present, depending on the legal framework of the country:• An ADD site may be licensed as a manufacturer (company) or a pharmacy (direct dispensing or
preparing and distributing);• The scale of the operation may be the deciding factor for whether an ADD site can operate as amanufacturer or pharmacy;• In some countries only pharmacies are permitted to prepare and supply ADD medicines and they
may or may not be permitted to supply medicines to other pharmacies.

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D. Licensing: The decision on the requirements for authorising/ licensing an ADD site should be taken at anational level and should take account of the licensing system and legislation in place in the relevant
country, and the content of these guidelines.

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ADD should only be carried out at a licensed site, i.e. a licensed manufacturer or pharmacy. Large scale ADD
should be carried out in a licensed manufacturer. An ADD site may receive an exemption from requiring a
manufacturing authorisation if it is a pharmacy. In general, to be classified as a pharmacy, a site should only
be supplying ADD medicines to patients of the pharmacy, and other pharmacy activities should occur at thesite i.e. the supply of medicines directly to patients/carers and associated patient care activities. The
distinction between a manufacturer and pharmacy should be decided on a national basis, depending on thescale, setting and other operations occurring at the ADD site.

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Due to the additional requirements for ADD, e.g. specific training requirements and labelling of the pouch/

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container with dosage instructions for individual patients, it is recommended that national authorities
provide a specific authorisation/licence for ADD activities that occur in manufacturers or pharmacies.
Authorities could suspend or withdraw the licence depending on compliance with its conditions. Inspection
prior to licensing, re-inspection at relevant intervals and the maintenance of a national register of ADD
sites is recommended.

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Where a site, e.g. a pharmacy, is commencing ADD activities and there is no requirement for an additional
licence, they should at a minimum be required to notify the relevant authorities of their intentions inadvance of commencing ADD activities and to provide regular updates or reports on their ADD activities.

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E. Standards: If an ADD site is a licensed manufacturer or distributor, GMP and, if applicable, GDP must be
adhered to. If the site is not a licensed manufacturer or distributor but is operating on an industrial scale orinvolved in external supply it is recommended that the site is licensed as a manufacturer, to ensure
adherence to GMP and GDP. If an ADD site is operating on a smaller scale and fulfils the relevant
requirements, it may operate as a pharmacy and these guidelines and the relevant principles of GMP and
GDP required to ensure that the quality, safety and efficacy of the ADD medication is maintained should beapplied.

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F. Product Liability and ADD Suitability Information from Manufacturers: A manufacturer’s productliability5 often does not extend to the use of their medicinal products in ADD unless relevant testing has
occurred and a product’s suitability for ADD is included in the product’s marketing authorisation data. It is
recommended that national authorities require marketing authorisation holders to include relevant stability
data, and data regarding the suitability of a medicinal product for use in ADD, in the product’s marketing
authorisation data. This data should indicate how long the medicinal product may be removed from its
original packaging and exposed to defined environmental conditions without quality impairment, and adviseof any supplementary measures required to protect the removed medicinal product from deterioration e.g.
for hygroscopic or light sensitive medicinal products. If applicable, additional testing should take place tocheck interactions with common packaging materials, other medicinal products which are dispensed
together and ADD equipment.

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Where sufficient information on the suitability of a medicinal product for ADD is not included in the
medicinal product’s marketing authorisation, the liability for its use in ADD (including storage for ADD) does
not sit with the manufacturer, unless the starting medicinal product is defective. The manufacturers’
original packaging has been approved as part of a medicinal product’s marketing authorisation and when amedicinal product is repacked into an ADD, it is being used outside of the product’s marketing
authorisation. In this context consideration should be given to the professional issues, including potential
legal liability issues that may arise in providing this service.

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At EU level, the Product Liability Directive applies to ADD if the starting medicinal product used in ADD is defective:
Council Directive 85/374/EEC of 25 July 1985 on the approximation of the laws, regulations and administrative
provisions of the Member States concerning liability for defective products (OJ L 210, 7.8.1985, p. 29–33).

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PART ONE: AUTOMATED DOSE DISPENSING: STANDARDS PERTAINING
TO THE ADD SITE AND OPERATIONS

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The packaging /repackaging of medicinal products traditionally occurs in a pharmaceutical (licensed)
manufacturer operating in accordance with GMP. GDP is also applicable where the external distributionof medicinal products occurs. In different countries in Europe, ADD practices currently occur in different
settings, including licensed manufacturers or companies and pharmacies in ambulatory and hospitalsettings.

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Regardless of the scale of production or the setting in which the ADD site operates, the ADD site mustensure that the quality, safety and efficacy of the medication dispensed into an ADD is maintained andmeets the standards that can be achieved by adhering to the principles of GMP, GDP and the content ofthese guidelines. If an ADD site is a licensed manufacturer or distributor, GMP and, if applicable, GDP must
be adhered to.

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4. PERSONNEL AND TRAINING:

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A. General: The responsible person at an ADD site must establish and maintain a system of quality
assurance and ensure t hat the ADD facility operates according to appropriate standards.
Successful operation of this system is dependent on qualified personnel carrying out the tasks forwhich the ADD site is responsible. An organisational chart for the ADD site should be in place and should
contain clear definitions of roles, duties, responsibilities and job descriptions. Responsibilities should beclearly understood by individual staff members and documented. All personnel should be aware of theprinciples of the ADD guidelines, relevant GMP and GDP, and receive initial and continuing training, a s
relevant to their individual role.

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The ADD site should have an appropriate number of staff with the necessary qualifications andpractical experience to ensure that ADD is carried out effectively. Appropriate responsibilities should beallocated to these staff members. Managing or supervisory staff should have specific ADD-related job
duties included in their job descriptions and have appropriate authority to carry out their responsibilities.
Their duties may be delegated to designated deputies of an appropriate qualification level. There should
be no gaps or unexplained overlaps in the responsibilities of those staff members involved in operation
processes, quality control and quality assurance.

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B. Responsible Pharmacist: Every ADD site should have a designated pharmacist who is responsible for the
management of all activities relating to the pharmaceutical process at the ADD site. The nominatedresponsible person must be a licensed/registered pharmacist in the country in which the ADD site is
located. They should have sufficient knowledge of ADD standards, be available at the ADD site during all
activities involved in dose dispensing and should supervise critical steps and take critical decisions
personally. The responsible pharmacist should be notified to the relevant authority. A deputy should bedesignated and available in the absence of the responsible pharmacist.

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The responsible pharmacist must ensure that medication is dose-dispensed in accordance with current
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ADD standards and the initial order and/or prescription. He/she can delegate certain tasks, such as
checking finished ADD doses to another pharmacist, however, critical decisions must be taken by the
responsible pharmacist personally.

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The responsible pharmacist approves and ensures the implementation of all processes, policies,
procedures and instructions that are part of the quality system, including:• Compliance with all relevant legislation and standards/guidelines, including medicines legislation, any
specific ADD medication legislation and other relevant legislation, e.g. data protection legislation;• The implementation of processes relating to the dispensing process;• The selection of medicinal products suitable for ADD;
• Monitoring and control of the dispensing environment;• Setting and monitoring of storage conditions and storage times for all stages of the process, i.e.
starting materials before deblistering, intermediate doses and dispensed ADD medication;• Hygiene and cleaning instructions;• Specifications and quality control procedures for all materials including packaging materials, medeicinal
products before dispensing, intermediate doses and dispensed ADD medication;• Master validation of ADD orders and prescriptions (for suitability to be dose-dispensed for an individual
patient) and of production and control equipment and related software;• Contracts with external parties, clearly setting out responsibilities of the different parties;• Authorisations to personnel, i.e. assignment of duties in line with expertise, qualifications and further
education/training.
The above mentioned tasks of the responsible pharmacist cannot be delegated.

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Furthermore, the responsible pharmacist is required to:• ensure the correct implementation of the ADD orders/prescriptions and, where this is done
automatically, approve the validation of the process;• ensure that medicinal products for the ADD prescription/order are received, deblistered, dose
dispensed, checked, controlled, released and supplied according to the appropriate standards anddocumentation;• ensure that ADD prescriptions are reviewed as appropriate for the patient and that the patient/carer
receives all necessary counselling on the use and storage of the ADD medication (may be delegated toa dispensing pharmacy if this is in accordance with local or national policy and/or is clearly stated incontracts);• ensure that all ADD medication is checked and compliance of the dispensed medication with theprescription/order is confirmed by an authorised person;• ensure that all necessary checks occur and records are signed by the responsible pharmacist or deputy
pharmacist before ADD medication is released;• ensure premises and equipment are adequately maintained;• ensure that the appropriate external and internal validations occur, including that all machines andsoftware systems are validated;• ensure a sufficient number of pharmacists and other appropriately qualified and trained
personnel are available for the type and volume of activity occurring at the ADD site;

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• ensure that the required initial and continuing training of personnel is carried out and adapted
according to need.

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Depending on the scale of operations, the responsible pharmacist may delegate certain tasks to otherauthorised personnel. However, only duties can be delegated – not responsibilities.

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C. Training: The ADD site should provide training for all personnel involved in storage, warehousing,deblistering, dispensing, control and supply and those accessing those areas (including technical,
maintenance and cleaning personnel), and for other personnel whose activities could affect the quality ofthe product. Training should be standardised for all ADD sites as far as possible, however the content andextent of training may vary depending on the scale and setting of the ADD site.

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Besides introductory training on the background, theory and practice of ADD and the pharmaceuticalquality assurance system, newly recruited personnel should receive training appropriate to the duties
assigned to them. All staff should be trained in the ADD site’s policies and procedures as relevant for
their role, and training content should be approved in accordance with internal procedures.

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The concepts of quality assurance, critical control points and all measures for their implementation should
be comprehensively addressed during the training sessions. Staff should be retrained at regular intervals,
e.g. when a process changes or new training needs are identified, and at a minimum annually. The
responsible pharmacist should also keep his/her knowledge of ADD up-to-date through regular training.

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Training programmes should be available and training should only be provided by persons with sufficientqualifications and knowledge in the relevant area. Personnel working in areas where contamination
should be avoided, e.g. clean areas or areas where medicinal products with strongly-acting, infectious or
sensitising substances are handled should receive specific training. Training for each individual assigned task
is necessary and staff should pass a qualification test and be provided with written authorisation prior tocommencing an activity. Dated training records should be maintained. The practical effectiveness of training
should be periodically assessed and staff should be encouraged to obtain additional relevant qualifications.

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Untrained personnel should not be permitted entry into the operational areas. If this is unavoidable, theyshould be given information in advance, particularly about personal hygiene and wearing appropriate
protective clothing.

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D. Elements of Introductory ADD Training for Different Staff:
Pharmacist(s): Specific training on quality systems, risk management, validation, stability, medicine
suitability, GMP, GDP, ADD standards and any other area the responsible pharmacist identifies as a gap inknowledge. Pharmacists should engage in continuing professional development in ADD appropriate totheir role. They should receive training in the ADD process and the patient care elements of ADD toensure their knowledge is maintained at the highest level.

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Pharmacy Technician(s): Specific training on critical control points, quarantine, corrective andpreventative actions, validation, documentation systems, and the “Plan Do Check Act (PDCA) principle”

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and any area in which they operate where a gap in their knowledge is identified.

413
414
415
416

Other staff: The purpose of medicinal products and ADD, hygiene, equipment, procedures, instructions,records, labelling, principles of one direction flow, critical square area (only one medicine or label in acertain space) and double checks.

417
418

5. PREMISES AND EQUIPMENT:

419

A. General: Premises and equipment must be located, designed, constructed, adapted and maintained tosuit the operations to be carried out. Their layout and design should minimise the risk of errors and permit
effective cleaning and maintenance, in order to avoid cross-contamination, build-up of dust or dirt, and ingeneral, any adverse effect on the quality of products. It should be designed in such a way as to prevent
adverse outside influences, especially contamination of premises, equipment, medicinal products or
packaging. Every site should establish a hygiene programme, which should be adapted to the activities tobe carried out in the facility and based on current best practice.

420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436

B. Premises: Premises should be situated in an environment which, when considered together withmeasures to protect the operations, presents minimal risk of causing contamination of materials or
products. All fixtures and fittings must be suitable for the intended purpose, of sound construction andcompliant with all health, safety and environmental requirements. The finish of all fixtures and fittingsmust be professional, complete and well maintained. All walls, floors, ceilings, plaster and paintwork mustbe safe, non-shedding, easily cleanable, and clean. All surfaces that come in contact with medicinal
products at any stage of the process, such as primary packaging materials, canisters, trays and interior
surfaces of machines and equipment should be smooth, free from cracks and open joints, should not shedparticulate matter and should permit easy and effective cleaning and, if necessary, disinfection.

437
438
439
440
441

Premises should be carefully maintained, ensuring that repair and maintenance operations do notpresent any hazard to the quality of products. They should be cleaned and, where applicable, disinfectedaccording to detailed written procedures. Premises should be designed and equipped so as to afford
maximum protection against the entry of pests, i.e. insects or other animals.

442
443
444
445
446
447
448
449

Light fittings, information technology cables, ventilation points and other services should be designed andsituated to avoid the creation of recesses which are difficult to clean. As far as possible, for maintenancepurposes, they should be accessible from outside the operating areas. In cases where dust is generated,
specific provisions should be in place to avoid cross-contamination and facilitate cleaning. Lighting,temperature, humidity and ventilation should be appropriate and such that they do not adversely affect,
directly or indirectly, the quality of the medicinal products during packaging and storage, or affect theaccurate functioning of equipment.

450
451
452
453
454

Layout of the premises should ensure the responsible pharmacist can adequately supervise all activities
at the ADD site. All steps of the ADD process should occur in areas connected in a logical order,
corresponding to the sequence of the operations, thereby facilitating one direction workflow from thestart to the end of the process.

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455
456
457
458
459
460
461
462
463

ADD should not be carried out in the same area as other activities. Designated rooms or segregated areas
should be provided for each stage of the ADD process, i.e. deblistering or any other removal of medicinal
products from their containers, operating the ADD machine (filling and dose dispensing), dose checking,and storage etc. Whether dedicated rooms or segregated areas are necessary should be decided basedon an assessment of the scale, type of medication, and operation of the ADD site. All areas used in the
ADD process should enable orderly and logical positioning of equipment and materials so as to reduce therisk of mix-ups between different medicinal products, unit doses or labels, avoid cross-contamination andreduce the risk of omission or incorrect application of any of the deblistering, dose dispensing or control
steps.

464
465
466
467
468
469
470
471
472
473
474
475
476
477

Unauthorised persons should not be permitted to access the ADD site. In particular, storage, deblistering,dose dispensing control and dispatch areas should not be accessed by personnel who do not work inthem. Every person entering the dose-dispensing areas should wear protective garments appropriate tothe operations being carried out, e.g. clothes, gloves, mouth masks, head covers.
C. Deblistering and Dispensing Area: Deblistering, dispensing and checking areas, should be
separated and effectively ventilated, with air control facilities (including ai r filtration) appropriate to the
products handled, the operations undertaken and the external environment. During the deblistering anddispensing process, i.e. the intermediate dispensing into storage containers, canisters and trays for
subsequent ADD, preventive measures should be applied to avoid cross-contamination (including throughthe dust of medicinal products) and to facilitate cleaning. Areas should be well lit, particularly where finalvisual checks are carried out. In-process controls may be carried out within the dispensing area e.g. on
sealing or printing, provided they do not increase the risk of errors in the ADD process.

478
479
480
481
482
483
484

D. Storage Areas: Storage areas should be of sufficient capacity to allow orderly and segregated storageof the various categories of materials and products: starting medicinal products, packaging materials, deblistered medicinal products, m e d i c i n e s i n quarantine, released, rejected, returned or ADD medication
recalled after supply. Storage areas should be clean and dry and maintained within acceptabletemperature limits. Medicinal products should not be stored on floors and shelving should be nonshedding.

485
486
487
488
489
490

Reception and dispatch areas should protect materials and products from the weather. Reception areas
should be designed and equipped to allow containers of incoming materials to be cleaned, where
necessary, before storage. Quarantine is usually ensured through physical quarantine. Any system replacing
the physical quarantine should provide equivalent security. Where quarantine status is ensured bylabelling or storage in separate areas, the status must be clearly marked.

491
492
493
494
495
496
497

E. Ancillary Areas: Rest and refreshment rooms should be separate from other areas. Facilities forchanging clothes and for washing and toilet purposes should be easily accessible and appropriate for thenumber of users. Toilets should not be directly accessible from production or storage areas. Maintenanceworkshops should, as far as possible, be separated from operating areas. Whenever parts and tools are
stored in the production area, they should be kept in rooms, lockers or other segregated areas reserved
for that use.

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498
499
500
501
502
503
504
505

F. Equipment: Appropriate equipment must be in place for the safe and efficient operation of the ADD
site, including deblistering apparatus, intermediate storage containers, medicine trays, opaque storage
containers, ADD machine, checking machines (depending on scale of operation), protective equipment,
cleaning equipment, information technology equipment and any other necessary equipment. Deblistering,
dispensing and control equipment should be designed, located, validated and maintained to suit its
intended purpose. Repair and maintenance operations should not present any hazard to the quality ofthe products.

506
507
508
509
510
511

Equipment should be designed so that it can be easily and thoroughly cleaned. This applies to all ADD
equipment and all contact surfaces, including deblistering equipment, ADD machines, cassettes, canisters,other containers and the repair station. Equipment should be cleaned according to written and validated
procedures, and stored only in a clean and dry condition. Washing and cleaning equipment should not bea source of contamination, either because of design or use.

512
513
514
515
516

Equipment should be installed in such a way as to prevent any risk of error or of contamination.
Equipment should not present any hazard to medicinal products. The parts of the production equipmentthat come in contact with medicinal products must not be reactive, additive or absorptive to such an
extent that it will affect the quality of the product and thus present any hazard.

517
518
519
520
521

Balances and measuring equipment of an appropriate range and precision should be available fordeblistering, dispensing and control operations. Measuring, weighing, dispensing, recording and control
equipment should be calibrated and checked at defined intervals by appropriate methods. Adequate
records of such tests should be maintained.

522
523
524

Defective equipment should, if possible, be removed from deblistering, dispensing and control areas, orat a minimum be clearly labelled as defective and put in quarantine.

525
526

6. PRESCRIPTIONS:

527

A prescription, or other valid authority, to supply medicinal products via ADD, written by an authenticateddoctor or healthcare professional with the authority to prescribe, must be available at the ADD site prior
to dispensing. In some countries, where two entities are involved, the prescription is transferred into a
medication order prior to dispensing and this order is transferred to the ADD site. In this instance a copyof the prescription should also be supplied.

528
529
530
531
532
533
534
535
536
537
538
539

Prescriptions and any ADD supply orders are required to meet the requirements of applicable legislation
and any pharmaceutical and clinical requirements. Particular attention should be paid to the period ofvalidity, any specific requirements relating to the medicinal products prescribed (e.g. controlled drugs)
and permissions related to generic substitution. Non-prescription medicinal products, vitamins and foodsupplements do not require a prescription, however if they are to be included in ADD, they should be
included in the prescription and order for the ADD medication. A prescription which is valid for repeat
dispensing should be returned to the patient/carer in line with the national legislation and practices.

540

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541
542
543
544

Double checking of the prescription details against computerised systems, orders, the medicinal products
and ADD patient labels should occur at relevant stages throughout the process, including at a minimum
when prescription details are entered into the ADD site’s computerised system and at the final dispensing
stage where medicines are released.

545
546
547
548
549

Electronic prescribing and order transmission is used for ADD in some countries. The security andprotection of personal data transferred using an electronic system must be maintained. Data scramblingand decoding of password protected details or another appropriate method may be used to ensure thesecurity and confidentiality of personal information.

550
551

7. MEDICINAL PRODUCTS: TRACEABILITY, SUITABILITY AND STABILITY:

552

A. Traceability of Medicinal Products: An ADD site must source its medicinal products from approved
suppliers in accordance with national regulations, i.e. authorised wholesalers or manufacturers. This isnecessary in order to ensure the security and integrity of the supply chain, and to ensure the quality,
safety and efficacy of the medicinal product sourced. Distributors should supply the ADD site withconsignment documents for the last step of the distribution chain.

553
554
555
556
557
558
559
560
561
562
563
564
565

Every ADD site should operate a comprehensive, auditable system for the sourcing, receipt and distributionof medicinal products. The authenticity of suppliers should be verified prior to their use and a list of theauthorised suppliers of the medicinal products should be maintained and routinely reviewed and verified
as part of the quality management procedures. Documentation should be available which permits clear
identification of the supplier of each consignment of medicinal products received by the ADD site and of
the medicinal products therein, e.g. supplier invoices. Such documentation should be retained. Records
should be adequately detailed and/or any additional necessary information should be available from the
suppliers.

566
567
568
569
570
571
572
573
574
575
576
577
578

All medicinal products should be delivered to the ADD site in accordance with GDP. They should bechecked for authenticity on receipt, in accordance with a written procedure. They must have amarketing authorisation issued by a competent authority. Under the Falsified Medicinal Products Directive(2011/62/EU) all medicinal products with a bar code safety feature will have to be decommissioned(checked for authenticity) at the ADD site. For non-EU Council of Europe (CoE) member states it isrecommended that the spirit of the directive is followed to avoid the infiltration of counterfeit/falsified
medicinal products in the course of ADD. Medicinal products should also be checked to ensure nodamage occurred during the delivery process. Appropriate follow up action should be taken in line with
the Directive (or its spirit for non-EU countries) if it is suspected that an ADD site has been offered or
received counterfeit, defective or inappropriately authorised medicinal products. This action should
include contacting the competent authority, segregating the product from legitimate stock and storing it
in a designated quarantine area.

579
580
581
582

Throughout the ADD process, primary and secondary packaging materials and patient information leaflets
should be handled and disposed of in a manner that prevents misuse, i.e. prevents access to materials
which could potentially be used for falsifying (counterfeiting) medicinal products.

583

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584
585
586
587
588
589
590
591
592

The ADD site should maintain adequate records to ensure the full traceability of every individual dosedispensed medicinal product, from receipt of the medicine through deblistering, intermediate storage,
ADD dispensing, to the distribution of the finished dose dispensed medication to the patient. Relevant
information, including the name and contact information for the patient, the product name, strength, batch
number, expiry date, product authorisation number etc. should be recorded for all medicinal products. It
is important that the batch number of the product is accurately recorded to facilitate the efficient recall ofa product. The record must be unalterable, easily searched and retrieved, in order to accurately identify
patients who have been supplied with a particular batch of a medicinal product where necessary.
Adequate records should also be maintained for packaging materials.

593
594
595
596
597
598
599
600
601
602
603

B. Suitability of Medicinal Products and Packaging Materials for ADD:
Medicinal Products: It is recommended that national authorities require the inclusion of relevant data
regarding the suitability of a medicinal product for use in ADD systems in a medicinal product’s marketing
authorisation data. A medicinal product which does not have information on its suitability for ADD included
in its marketing authorisation, should only be removed from the manufacturer’s original packaging (e.g.
deblistered) for use in ADD if sufficient, accurate data is available to make a suitability assessment
and if it has been approved for this purpose by the responsible pharmacist. In general, solid single-dose
oral dosage forms with good physical, chemical and pharmaceutical stability may be used in ADD,
provided that they are stable outside the original primary packaging at room temperature during aperiod covering deblistering, storage, dispensing, supply and use.

604
605
606
607
608
609

The release by the responsible pharmacist should be based on a documented and suitably verified risk
assessment of the medicine's suitability taking into consideration, if available:• Data provided by the marketing authorisation holder, either in the medicinal product’s Summary of
Product Characteristics (SmPC) or other available data;• Data or lists provided by a national or local competent authority.

610
611
612
613
614
615
616

If the above information is not available, the decision to include a medicinal product in ADD must be basedon a risk assessment performed by the ADD site. This risk assessment should assess the potential risks to
the quality, safety and efficacy of the medicinal products and take into consideration:• Data from recognised international sources, e.g. from competent authorities in another country;• Data from literature or reference books, e.g. Ph. Eur. (European Pharmacopoeia), BP (British
Pharmacopoeia), USP (US Pharmacopoeia) or other reputable sources.

617
618
619
620
621
622
623
624

A more extensive risk assessment is required prior to the inclusion of a medicine with little available
stability data and/or a new medicinal product in an ADD system. The crucial criteria for assessing thesuitability of a medicine for ADD include:• Physical, chemical and pharmaceutical stability of the medicine from deblistering, throughintermediate storage, dispensing/repackaging and distribution to the patient;• Toxicity of the medicine and potential for cross-contamination;• Potential for physical and chemical interaction with other medicinal products.

625
626

Each medicinal product should be assessed individually with regard to:

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627
628
629
630
631
632

•
•
•
•
•
•

Chemical and physical properties of the active ingredients and/or the excipients;
Manufacturing procedures;
Formulation/dosage form;
Containers and closures;
Proposed storage conditions;
Stability influenced by the use or absence of antioxidants or preservatives.

633
634
635

Medicinal products with little available stability data or medicinal products never previously used in ADD
should be assessed with particular care.

636
637
638
639
640
641
642
643
644
645
646
647
648
649
650

In addition, the following decisions should be taken and documented by the responsible pharmacist:• If medicinal products which have potential for misuse or abuse, e.g. controlled drugs or psychotropic
medicines, can be included. These medicinal products should only be included if adequate procedures toprevent their misuse/abuse are in place.
• If vitamins, minerals and other food supplements can be included in ADD. Where these products areavailable as authorised medicinal products these must be used in preference to any unauthorised
version. Caution should be exercised with unauthorised supplements.
• If split units of medicinal products can be dispensed. Only tablets scored for dividing, or tablets withappropriate information from the marketing authorisation holder on their suitability for splitting, shouldbe split for ADD. In principle split tablets should only be used if no authorised medicinal product or otheralternative is available.
• If a medicine is suitable for inclusion in a multidose container or should be packaged alone. Medicinesthat may be considered unsuitable include unauthorised products such as supplements and split tablets,
unstable medicines, controlled drugs and medicines that should not be handled.

651
652

If local or national regulations apply, these must be considered prior to making decisions.

653
654
655
656
657
658
659
660
661
662
663

Certain medicinal products should be excluded from ADD unless the potential risk connected with their use
can be overcome by special precautionary measures:• Physically unstable medicinal products: e.g. tablets that break or crumble easily, effervescent or
dispersible tablets, sublingual or buccal tablets, hygroscopic and thermo or light sensitive tablets. Large
tablets can’t be included in some systems.
• Medicinal products with a high risk for cross-contamination: highly active, highly toxic or highly
sensitising tablets, such as certain hormones, cytotoxic and/or embryotoxic medicinal products or
antibiotics, e.g. penicillins and cephalosporins.
• Medicinal products that are not suitable due to patient care issues, e.g. medicinal products dispensed forintake “as required” or according to an irregular schedule.

664
665
666
667
668
669

Precautionary measures which should be considered prior to dispensing a medicine via ADD:
• Retaining the medicinal product in its primary packaging (not deblistered): e.g.for tablets with highfriability; dispersible, effervescent, sublingual or buccal tablets;• Inserting a desiccant in the ADD container/canister for intermediate storage: hygroscopic medicinal
products;
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670
671
672
673
674

• Using dedicated equipment: highly active, highly toxic or highly sensitising tablets;• Inserting the medicinal products into the ADD machine using a manual tray;• Removing the primary packaging just before adding the medicine to the manual section of the ADD
machine: e.g. certain soft-gelatin capsules;• Tablets used in ADD should be coated where possible.

675
676
677
678
679

All suitability assessments, precautionary measures, special instructions and decisions should be written
in adequate detail, approved by the responsible pharmacist and made available to all relevant personnel
in a suitable form. Self-inspections or audits should be carried out and documented to ensure that thesuitability assessments, decisions and precautionary measures have the intended effect.

680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700

Packaging Materials: Consideration of the quality of packaging material is an integral aspect of theassessment of the appropriate duration for the storage for medicinal products. All packaging materials
used in ADD should be assessed for their suitability and released for use with specific ADD medication inaccordance with the site’s packaging materials specifications. This is particularly important for packaging
materials that come into direct contact with medicinal products. The assessment should, at a minimum,
consider and document the suitability of the material for packaging medicinal products, including thematerial’s certification for pharmaceutical use and whether it provides appropriate protection against theenvironment, humidity and oxygen, and where necessary, against light. The specifications for the
packaging material used, including all critical parameters such as moisture and oxygen permeability, thenumber, quality and thickness of layers of material and, where relevant, information on light protection,
should be available at the ADD site. The finished dispensed doses should be packed in packaging materials
which provide sufficient protection during storage and transport and allow easy removal and opening by
the patient or carer. For longer periods of storage, it is important that the quality of the packaging material
is similar to the original packaging of the registered medicinal product(s). The purchase, handling andcontrol of packaging materials must be carried out according to the ADD dispensing site’s
specifications. Roll-feed labels are normally preferable to cut labels to avoid mix-ups.
C. Stability of Medicinal Products: National authorities are advised to require marketing authorisation
holders to include information on a medicinal product’s stability after it is removed from its primary
packaging in the SmPC.

701
702
703
704
705
706
707

For each medicine, the ADD site’s responsible pharmacist defines the storage conditions and the
maximum storage time for the deblistered m e d i c i n e s and the ADD dispensed medicines according toa procedure. This procedure must assess the impact of removing the medicine from its primary packaging
on the quality, safety and efficacy of the medicinal product. Specifications for the storage conditions should
ensure the quality and stability of a medicinal product is not impaired after removal from the original
primary packaging.

708
709
710
711
712

Stability data included in a medicinal product’s SmPC and/or national standards on the stability of
medicinal products take precedence over stability information from other sources. If there is no stability
information in the SmPC, marketing authorisation holders should provide any available stability
information to ADD sites.

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713
714
715
716
717
718
719
720

In the absence of appropriate stability data, medicinal products should be removed from their primary
packaging for the shortest time possible. Particular care must be taken to ensure that these medicinal
products are stored under controlled conditions in accordance with the relevant specifications, e.g.
temperature, humidity, light protection. Other options, such as ADD of medicinal products in their primary
packaging should also be considered. Any stability information available on split tablets andsupplements should be considered prior to their inclusion in ADD. These products should also be removed
from their primary packaging for the shortest time possible.

721
722
723
724
725
726

ADD dispensing and supply to patients should occur regularly and doses should not be supplied to patients
more than one month prior to their date of use (the default expiry date of the medicine once removed
from its primary packaging). The frequency of supply should be agreed with the prescriber and reflect
patient need and the characteristics of the medicinal products involved. Weekly dispensing is
recommended.

727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751

The maximum storage time for deblistered and ADD dispensed medicinal products should be set basedon a documented quality risk assessment taking into account, at a minimum:• Local and national requirements;• Information in the medicinal product’s SmPC or other information from the manufacturer;• Other stability data from reputable sources, where available or required;• Characteristics of the medicinal product;• Packaging materials;• Storage conditions;• Potential for interactions with other medicinal products, supplements or packaging materials;• The time between dispensing and use of the medication by the patient.
Each medicine, including medicinal products stored after deblistering in containers for intermediatestorage, in canisters in ADD machines and finished ADD dispensed doses, must bear an expiry date foruse, based on a justified decrease of the expiry date of the original medicinal product. In the absence ofspecific national or local requirements, stability data from manufacturers, requirements in monographs orother reputable stability data, it should be assumed that the expiration of the ADD dispensed medication issignificantly reduced. Intermediate deblistered medicines stored under controlled conditions at the ADD
site should not be stored for longer than two months unless an appropriate assessment demonstrates
that stability is definitively maintained beyond this time. No medicine should be stored for longer thansix months from the date of removal from the primary packaging to the date of use, and the expiry dateassigned must not exceed the original expiry date. Whatever expiry date is assigned there should be
documented proof supporting the decision. Suitable measures must be taken to ensure that expired
medicinal products are not used in ADD. Medicinal products should not be used for ADD within the lastmonth of the expiry date of the product.

752
753
754
755

D. Use of Multidose ADD Pouches/Containers: National authorities may provide recommendations on the
medicinal products that should be packed individually and on the maximum number of medicinal

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756
757
758

products that should be packed in one container. They may also recommend that certain medicinal
products, e.g. highly active, highly toxic or highly sensitising medicinal products, controlled drugs andunstable tablets, should not be packed with other medicinal products.

759
760
761
762
763
764
765
766
767
768
769
770

The ADD site should consider the potential impact of packing a number of different medicinal products
together in one container/pouch on the stability of these medicinal products. The responsible pharmacistat the ADD site should define the maximum length of time medicinal products should be packed together
and what medicinal products should not be packed together. As a minimum, issues to be considered
include cross-contamination, chemical and physical interactions, whether compatibility testing is necessary
and if the medicinal products can be distinguished during the checking process (e.g. by colour, shape, size,
inscription, markings or weight). Other factors include the size of the medicinal products relative to thespace available and the amount of information that can be safely printed on the pouch/ container/ label.
An ADD site should maintain a list of which medications should be packed individually. Decision making
should be based on information from manufacturers, any relevant local or national regulations, standards
or requirements and information from other reputable sources.

771
772
773
774
775
776
777

E. Exchange of Stability Data: There should be national and international exchange of ADD suitability
assessments, stability data and compatibility studies between competent authorities, marketing
authorisation holders and ADD dispensing sites to ensure access to the most recent information. All
technical information and medicinal product relevant factors, which are important for comparability of thedata, should be exchanged, e.g. details of the type of ADD technology used and different specifications for a
medicinal product (excipients and form).

778
779

8. AUTOMATED DOSE DISPENSING PROCESS:

780

A. General: ADD must follow clearly defined procedures, which ensure that the medicinal products arepackaged in accordance with the relevant order/prescription. Special attention is required to prevent mixups, to maintain the storage conditions, to ensure the stability of the medicinal products and to avoid
microbial or cross-contamination.

781
782
783
784
785
786
787
788
789
790
791
792

Any problem which might adversely affect the quality of a medicinal product or material should be
investigated, recorded and reported to the responsible pharmacist. Incoming medicinal products andmaterials, deblistered medicinal products and ADD medication should be separated physically or by otherappropriate measures. All materials and medicinal products should be stored under the appropriate
conditions, in line with the marketing authorisation, and in an orderly fashion to permit batch segregationand stock rotation. Special precautions should be taken to prevent the generation and dissemination ofdust from the medicinal products. This applies particularly to the handling of high risk (highly active or
sensitising) medicinal products.

793
794
795
796
797
798

B. Prevention of Cross-Contamination: Contamination of a packaging material or medicinal product byanother material or product must be avoided. This risk of accidental cross-contamination mainly arises
from the uncontrolled release of dust from materials and other medicinal products in process, fromresidues on equipment, and from operators’ clothing. The importance of this risk is dependent on thecontaminant (e.g. certain hormonal, cytotoxic and other highly active medicinal products) and the

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799
800
801
802
803
804
805
806
807
808
809

medicinal product at risk of being contaminated. The use of coated medicinal products is recommended as
the risk of cross-contamination is lower than for uncoated medicinal products.
Cross-contamination can be avoided by appropriate technical and organisational measures, in cl u di n g:
• Having designated, segregated areas for deblistering and ADD;
• Excluding certain medicinal products from the process or handling them in their primary packaging;• Providing appropriate air extraction;• Reducing the risk of contamination caused by entry, re-circulation or re-entry of untreated or
insufficiently treated air;
• Using cleaning and decontamination procedures of known effectiveness.
Measures and procedures to prevent cross-contamination should be checked and evaluated at regularintervals for their effectiveness.

810
811
812
813
814
815

C. Deblistering: Removal of medicinal products from the original primary container (deblistering in the caseof a blister) can be required to prepare medicinal products for use in ADD. After deblistering, the units may
be stored before ADD in a container at the ADD site. Deblistering should be performed by designatedpersons according to written procedures and all of these activities should take place in an area segregatedfrom the dose-dispensing area.

816
817
818
819
820
821

Before starting the deblistering process and between the deblistering of different medicinal products anddifferent batches of the same medicinal product, line clearance (cleaning of the deblistering area andequipment) should be carried out and documented. Authorised personnel should approve line clearance
and the release of containers of deblistered medicinal products for the ADD process according tostandard procedures.

822
823
824
825
826
827
828
829
830
831

Deblistering requires that operators wear protective clothing to protect the product and themselves, e.g.
gloves, head cover and beard mask. Gloves should be of a material/fabric with non-adhesive properties.
Defective protective clothing should be replaced. Detailed written instructions must be followed byoperators. At the point of deblistering and filling, an appropriate air-flow circulation system or dust
extracting system should be in place and measures should be established to ensure temperature andhumidity is maintained within a specified range. Clean and properly labelled containers must be used for
deblistered medicinal products. Only one type of label identification is allowed in the deblistering or fillingarea at a time. In order to reduce errors throughout the deblistering process, additional precautionary
measures such as the use of colour coding may be helpful.

832
833
834
835
836
837
838

Prior to releasing a container with deblistered medicines for the ADD process, it should be double
checked, either by two people, by a person and a bar code check or by using another system which gives
the same assurance. Deblistered medicinal products should be checked against their original packaging,using the “four eyes’ principle”. Records of the deblistering process should include date and time of
deblistering, details of the medicinal product, operator, second operator, quantity deblistered, anddocumentation of cleaning and exceptional occurrences.

839
840
841

D. Storage of Deblistered Medicinal Products: A designated area should be provided for the storage ofdeblistered medicinal products. The maximum expiry date should be defined and easily identifiable for

26/09/2016

23

842
843
844
845
846
847
848
849
850

each product. The following information should be included on the product label or be traceable inanother manner:• Name, form and strength of the medicine;• Original manufacturer, product authorisation number and batch number;• Original expiry date;• Quantity;• ADD batch number;• Date of deblistering;• Newly assigned expiry date.

851
852
853
854
855
856
857
858
859
860

To avoid cross-contamination between medicinal products and batches, containers should be clean prior
to use and cleaned after use by validated cleaning methods. Only medicinal products with the same batch
number should be stored in the same container. Light and humidity protection measures during storage ofthe medicinal product should be established, e.g. use of an opaque container or desiccant. Temperaturein the storage area should be controlled, monitored and recorded. Humidity should be monitored andrecorded and if necessary controlled. The acceptable temperature and humidity range should be basedon requirements in the medicinal product’s SmPC. Where no specific requirements are stated theyshould be set by the responsible pharmacist taking into account the quality of the medicinal product aswell as aspects relevant to the ADD process. Records of these activities should be kept.

861
862
863
864
865

For a medicine that is not uniquely identifiable by shape, magnitude, inscription and colour, theaccompanying patient information leaflet could be placed, in a hygienic way in the intermediate container
and this could be used as part of the double check. Stock rotation should occur for deblistered stock andthe First Expired, First Out (“FEFO”) principle applied.

866
867
868
869
870
871
872
873
874
875
876

E: Dispensing Operations: Dispensing must be performed by designated persons according to written
procedures. Before any dispensing operation is started, measures should be taken to ensure that thework area and equipment are clean and free from any medicinal products, product residues or documents
not required for the current operation.
The written procedures should cover at least the following points:• Information on the ADD equipment;• Preparation of ADD equipment;• Detailed operating instructions;• Instructions regarding storage and labelling;• Any necessary precautionary measures.

877
878
879
880
881
882
883

For all canisters used in ADD machines a database/logbook with the following information should bemaintained:• Medicinal product name and strength;• Unique code;• Details of essential mechanical parts;• Calibration;

26/09/2016

24

884
885
886

• Start date of use;
• Details of repair or recalibration;• End date of use (canister).

887
888
889
890
891
892
893
894
895
896
897

For all medicinal products dispensed, including medicinal pro ducts included in the manual tray of
the ADD machine, double checking of the product’s identity and recording of the batch number isnecessary. In-process and environmental controls should be carried out and documented, e.g. monitoring
and control of the temperature within the ADD machine. Each dose-dispensed medication should betraceable from the name of the patient, pharmacy, distribution group (if applicable), machine, operator,
dispensed medicinal products, batch number and checks. The patient should be able to easily open thecontainer/ pouch containing the dose-dispensed medication. It is recommended that in-process checks be
made to confirm the easy removal and smooth opening of each dose. The relationship between the batch
number of the medicinal product(s), the batch number of the primary packaging material of the pouchand the batch number of the ADD medication should be traceable.

898
899
900
901
902
903

F. Checking Process: A combination of automated and visual checking of ADD medicine is recommended.
In particular, the use of automated checking equipment is recommended in large scale ADD sites. If
automated checking is not available, the ADD medication must be checked visually. Double checking should
always occur and can comprise of an automated/visual or visual/visual double check. Checking must be
carried out by authorised personnel in accordance with written procedures.

904
905
906
907
908
909

If automated checking equipment is used, it should be externally and internally validated prior to use
and at appropriate intervals afterwards. The checking equipment should be calibrated periodically andrecords of calibration maintained. The calibration software should be used on each medicinal product used
for ADD. Part of the authorisation of the personnel for visual checking should involve a test to
demonstrate appropriate eyesight and visual abilities.

910
911
912
913
914
915
916
917
918

The number and identity of the medicinal products, the integrity of the container and the labelling should
be checked. Medication should be checked against the original packaging and prescription/order. The dose
dispensed medication is either released for supply or rejected. The rejected medication must be removed
from the area and quarantined pending correction or disposal, e.g. if the quality of the medicinal products
is impaired or suspected to be impaired. It is recommended that a photograph is available for each dosedispensed medication unit that may be referred to in case of complaints. The number of ADD units(pouches) should be reconciled to ensure completeness of the packaging process against the number ofindividual medicinal products fed into the ADD system.

919
920
921
922
923
924
925
926

G. Correction of Errors: The ADD site should set in-house limits for errors and corrections. Rejected
medication should only be reintroduced back into the process after inspection, investigation and releasein accordance with procedures. All corrections should be carried out in line with written procedures. Errors
and corrective measures must be documented, analysed and regularly reviewed and preventive actions
should be taken to avoid similar errors in the future. The triggering event that caused the error should berecorded where known and should be included in the analysis. Preventive actions should include double
checking, reflection on training and other procedures, communication paths and other work routines. The

26/09/2016

25

927
928
929

following information should be recorded for each individual correction: date, time, operator or
pharmacy (if applicable), patient name, medicine, strength, number, type of mistake, person
undertaking the double check, expiry date etc.

930
931
932
933
934
935
936
937
938
939
940

H. Labelling and Information: In ambulatory/primary care settings, the following information should be
included on the final ADD medicines:• Name of the patient;• Dispensing pharmacy/ADD site;• Medicinal product name, strength and form;• Quantity of medicinal products;• Administration and dosing instructions;• Warnings and storage instuctions as applicable;• Date of dispensing/Expiry date of the medication/Date and time of medication use;
• Identification or batch number or electronic code to ensure full traceability.

941
942
943
944
945

Data may be printed on the final dispensed dose or, if adequate space isn’t available, on an associated bag,pouch or other container provided with the final dose. Information allowing for the identification of theindividual medicinal products dispensed should also be provided. The information on the label mustcomply with any applicable local or national regulations.

946
947
948
949
950
951
952
953
954
955
956

Relevant distribution information and identifying details should be printed on the outside of the containeror the associated packaging. This information should be sufficient to accurately identify the patient andshould include the patient’s name and address and if applicable or used as an identifier, their date of birth,
insurance number, distribution group and any associated pharmacy. Other information that can either be
printed on the labels or stored in the ADD site’s information system are the batch numbers of the individual
medicinal products, prescriber details, details of the dispensing pharmacy – if different to the ADD site –and additional patient or care centre details. Additional information on the ADD machine used, theoperator who prepared the ADD medicines, the checks performed and the pharmacist who carried out thechecks should be maintained in the information system of the dispensing organisation or in thecorresponding records.

957
958
959
960
961
962
963
964
965

I. Medication Release: To ensure the accuracy of dispensed ADD medication it is necessary for thepharmacist to check all critical elements of the process for each patient’s medication prior to approving
their medication for release and supply. Adequate checking and approval records should be maintained andshould clearly detail the critical parameters checked, the acceptance criteria for approval and the name of
the checking pharmacist. If an ADD site is a licensed manufacturer, ADD medication release must comply
with GMP and associated batch documentation and release requirements. The approval for supply ofdispensed ADD medication to patients can only be authorised by a pharmacist – either the responsible
pharmacist or a deputy pharmacist.

966
967
968
969

J. Validation: When new equipment, machines or information technology systems are introduced at the
ADD site, they should be validated regarding their suitability for use. T h i s i n c l ud e s equipment used forthe transfer of electronic prescriptions, information technology systems, deblistering equipment, ADD

26/09/2016

26

970
971
972
973
974

machines, control equipment and any other equipment which may have an impact on the consistentquality of ADD medication. The depth and extent of the validation should be determined on the basis ofquality risk management and should include DQ, IQ, OQ and PQ (Design Qualification, Installation
Qualification, Operation Qualification and Performance Qualification) as required. The process whenvalidated should produce a product which consistently meets the required quality.

975
976
977
978
979
980
981
982
983
984

Information technology systems or materials, which may affect ADD quality and/or the reproducibility ofthe process, should be validated after significant amendments t o the ADD process, including any change
in equipment. The labelling process should be validated; checks should occur at appropriate intervals toensure that electronic code readers, label counters and other similar devices are operating correctly.
Processes and procedures should undergo periodic critical re-validation t o ensure that they remain
capable of achieving the intended results. The results of validation studies should determine when thenext validation is required. If equipment does not perform as expected, it should be revalidated. Validated
cleaning methods should be used on critical surfaces of equipment, particularly in the deblistering anddispensing areas.

985
986
987
988
989

A master validation plan approved by the responsible pharmacist should be in place for the ADD site. The
validation criteria for all equipment and each process should be listed in the plan. Completion of the master
validation plan demonstrates that all machines used for production and quality control, and all IT systems,
cleaning methods and processes are validated.

990
991
992
993
994
995

K. Reconciliation Process: There should be records and/or inventory control in place to ensure that thequantities of different medicines handled at the ADD site are reconciled with deblistered medicinal
products, medicinal product quantities in stock, dispensed medication and waste medication. Any
deviations should be brought to the attention of the responsible personnel without delay, corrected andsuch corrections documented.

996
997
998
999

Reconciliation should be carried out after all important steps throughout the ADD process, i.e. deblistering;when medicinal products have been dispensed via ADD; after any changes t o ADD medication haveoccurred and at distribution. Records of these checks should be maintained.

1000
1001

9. DISTRIBUTION, SUPPLY TO PATIENTS AND RECALL:

1002

GDP should be applied to the distribution of ADD medication to pharmacies, patients or carers from ADD
sites. In some circumstances pharmacists may supply ADD medication directly to patients/carers; inthese circumstances the relevant elements of GDP required to maintain the quality of the medicinal
products supplied should be adhered to.

1003
1004
1005
1006
1007
1008
1009
1010
1011
1012

GDP should be implemented through a quality system operated by the ADD site, which ensures that:• the ADD medicines distributed are authorised in accordance with legislation;• storage conditions are observed at all times, including during transportation;• contamination from, or of other products, is avoided;• an adequate turnover of stored medicinal products takes place;• ADD medicines are stored in appropriately safe and secure areas.

26/09/2016

27

1013
1014
1015

In addition, the quality management system should ensure that the right products are delivered to the rightaddressee within a satisfactory time period.

1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031

The following minimum written information should be provided with ADD medication delivery dockets:• Date of delivery;• Quantity delivered;• Name and address of the ADD site;• Name and address of the patients;• Name and address of the pharmacy/institution (where applicable);• Duration of the ADD medication period;• Other identifying details as required.
There should be written policies, procedures and delivery agreements between the ADD site and addresseein place at the ADD site. These documents should clearly describe the distribution responsibilities of the
ADD site.Temperature monitoring and, if necessary, controlled delivery should be used. The assessment of
the level of temperature control required should depend on the medicinal products involved, the local
climate and the stability of the medicinal products. Temperature limits must be set and the temperatures
monitored and recorded.

1032
1033
1034
1035
1036
1037
1038
1039

ADD medications should be distributed promptly, safely and in a condition that is appropriate for use.
They must be packed, transported and distributed in such a way that their integrity, quality, safety andefficacy are preserved. The transport containers should be packed so that the packaged products are notdamaged during packaging or transportation. The distribution method must be secure and medicinal
products must be sealed in tamperproof containers. The containers used in transportation should becleaned as often as necessary. There should be a system (i.e. barcode or equivalent) in place to track thedelivery. Distribution processes should be checked and checks recorded.

1040
1041
1042
1043
1044
1045

The distribution method used should incorporate a verifiable audit trail for the ADD med ications fromthe point at which they leave the ADD site to the point at which they are received by the addressee. A
confirmation of the receipt of the ADD medication by the designated person(s) should be obtained, e.g.
a signature. This documentation should be retained for review at the ADD site. Records of distribut io nshould be kept.

1046
1047
1048
1049
1050

The distributer should inform the ADD site immediately if any delivery is missing, or o f any deviation
during the distribution which may affect the quality of the ADD medication. Records of issues identified
should be maintained and appropriate follow up actions/rectification of errors should occur. Misplaceddeliveries should be actively traced to their destination or returned to the ADD site.

1051
1052
1053

A procedure and tracing system should be in place which enables the identification of dispensing errors andthe recall of medication from patients to the ADD site.

1054
1055

26/09/2016

28

1056

10. WASTE MANAGEMENT:1057

Rejected starting materials and medicinal products should be clearly marked as such and put inquarantine in sealed or locked containers. They should be either returned to the supplier or destroyed as
appropriate.

1058
1059
1060
1061
1062
1063

To ensure that no rejected dose-dispensed medication is supplied, organisational measures, including
procedures and checking, should be implemented. The ADD site should accept the return of unused ADD
medication.

1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1074

Waste medication, e.g. expired, damaged or returned medication, must never be reused and should be
handled and stored separately from ADD medication stock. Waste medication should be clearly labelled
and stored in quarantine under the control of the responsible pharmacist. This will prevent unauthorised
access. Waste should be processed promptly into medicinal product waste bins, sealed when full anddestroyed, via controlled procedures in accordance with local/national regulations. Special attention shouldbe paid to confidential waste containing personal information such as information about individual
patients, prescriptions and used printing ribbon. Waste labelling, packaging materials and patient
information leaflets should also be stored securely and promptly destroyed in a controlled manner. All
necessary steps should be taken throughout the ADD process to reduce the risk of the reuse of waste
medicinal products and packaging.

1075
1076

11. QUALITY ASSURANCE:

1077

A. General: Quality Assurance is the sum total of the organised arrangements made with the objective ofensuring that medicinal products dispensed in ADD are of the quality required for their intended use.
Robust quality assurance is required throughout the entire process.

1078
1079
1080
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090

The ADD site must ensure that ADD medicines dispensed are suitable for use, comply withrequirements and do not pose risks t o patient safety and treatment efficacy. ADD sites must have anappropriate quality management system in place, based on the type of site, their licensing status and thescale of their operations. If an ADD site is a licensed manufacturer or distributor, GMP and, if applicable,
GDP must be adhered to. If an ADD site is operating on a smaller scale, the quality system should be basedon the principles of GMP and the content of these guidelines and, if distribution occurs, GDP. Irrespective of
the scale or setting, the quality management system must ensure that the quality, safety and efficacy of the
ADD medicines dispensed are maintained. Further decisions on what standards are needed to ensure thisshould be made on a national basis following an appropriate risk assessment and should take account of thecontent of these guidelines.

1091
1092
1093
1094
1095

There should be quality indicators and key performance indicators in place. Continual improvement isfacilitated through the implementation of quality improvements appropriate to the current level of process
and product knowledge. Regular risk assessments should be carried out at each stage of the process tofurther reduce the potential for errors.

1096
1097
1098

The responsible pharmacist should consider what principles are necessary to ensure the quality of the
ADD medication. The “one direction flow” principle (no crossing lines), the “critical square metre

26/09/2016

29

1099
1100

principle” (only one medicinal product or label in a certain area), double/triple checking for all criticalactions and other measures that reduce the risk of errors, should be applied.

1101
1102
1103
1104
1105

Procedures should be established for the prospective evaluation of planned changes and their approval
prior to implementation, taking into account regular notification and approval where necessary. After
implementation of any change, an evaluation should be undertaken t o confirm that the quality objectives
were achieved and that there was no unintended harmful impact on product quality.

1106
1107
1108
1109

Managerial responsibilities at different stages of the process should be clearly specified. The ultimate
responsibility for the approval, oversight, supervision and control of the quality system lies with the
responsible pharmacist.

1110
1111
1112
1113

B. Audit: Self-inspections should be conducted in order to monitor the implementation and compliancewith relevant GMP, these ADD guidelines, national standards and if applicable, with GDP, and to propose
necessary corrective measures.

1114
1115
1116
1117
1118

Personnel matters, premises, equipment, documentation, production, quality control, distribution of the
medicinal products, arrangements for dealing with complaints and recalls, and self-inspection, should be
examined at intervals following a pre-arranged programme in order to verify their conformity with theprinciples of quality assurance.

1119
1120
1121
1122
1123

Every deviation that may have an impact on the quality of the medicinal product should be investigated,assessed, documented and approved by the responsible pharmacist. With respect to the deviation
established, corrective and precautionary measures should be taken on the basis of quality risk
management.

1124
1125
1126
1127
1128
1129
1130
1131
1132
1133
1134
1135
1136

Self-inspections should be conducted in an independent and detailed way by designated qualified,competent personnel employed at the ADD site or by the ADD site owner. The frequency with which an
ADD site carries out self- inspections should be based on a risk assessment. Self-inspections should occur
at least on an annual basis, or more frequently in the case of ADD of medication carrying a higher risk, or
if there is a change in the process. Independent audits by licensed external experts are also
recommended. All self-inspections and external audits, and the corrective and precautionary measures
implemented, should be recorded.
C. Pharmacovigilance and Safety System and Data Collection: A specific pharmacovigilance and safetysystem for reporting ADD errors, incidents and adverse effects should be established. The system should becoordinated across Europe and encourage the sharing and analysis of data and comparison of the rate oferrors, incidents and adverse effects with traditional dispensing.

1137
1138
1139
1140
1141

Bar code technology and electronic patient medication records are often used in ADD and information
contained in these systems can include patient, medicine, prescriber, pharmacist and operator data.
Collection and sharing of this data (anonymised) is encouraged but must occur in accordance with dataprotection provisions.

26/09/2016

30

1142

12. DOCUMENTATION: POLICIES, PROCEDURES AND DATA COLLECTION

1143

A. General: Good documentation constitutes an essential part of the quality assurance system and is a
key element of compliance with GMP, GDP and these ADD Guidelines. The various types and formats of
documents should be defined in the quality management system. Paper-based, electronic orphotographic storage formats may be used. The main objective of a documentation system is to establish,
control, monitor and record all activities which directly or indirectly impact on the quality of ADD.

1144
1145
1146
1147
1148
1149
1150
1151

The quality management system should include sufficient instructional detail to facilitate understanding
and implementation of the requirements, in particular recording of the processes and situational
assessment.

1152
1153
1154
1155
1156
1157
1158
1159
1160
1161
1162

There are two primary types of documentation for managing and recording adherence to these ADD
guidelines and relevant GMP and GDP:
• Instructions (directions/requirements, procedures and specifications);• Records.
Good documentation practices should be applied. Suitable controls should be implemented t o ensure
the accuracy, integrity, availability and legibility of documents. Documents containing instructions should
be approved, signed and dated by the responsible pharmacist and be available to all relevant staff.
T h e y should have unambiguous contents, be uniquely identifiable, be laid out in an orderly fashion, beeasy to check, and the style and language of documents should be appropriate for their intended use. The
implementation and review date should be defined.

1163
1164
1165
1166

Standard operating procedures, work instructions and methods should be written in an imperative,
mandatory style. Documents within the quality management system should be regularly reviewed andkept up to date. Obsolete documents should be clearly marked and stored separately.

1167
1168
1169
1170
1171
1172
1173
1174
1175
1176
1177
1178
1179
1180
1181
1182
1183

B. ADD Documentation: There should be documents on policies, procedures, protocols, specifications,i n c i d e n t reports and follow-up actions, where appropriate, for the following processes:• Validation and qualification of processes including cleaning, equipment and systems;• Equipment assembly and calibration;• Maintenance and cleaning of equipment and facilities;• Personnel matters;• Training in ADD guidelines, relevant GMP and GDP and technical matters, as well as verification of theeffectiveness of training;• Protective clothing and hygiene;• Environmental monitoring;• Pest control;• Complaints;• Returns of ADD medication;• Change control and management;• Investigations of deviations and non-conformances.
• Patient care issues (consent, data protection, patient suitability assessments, medication therapy review

26/09/2016

31

1184
1185
1186
1187

•
•
•

1188
1189
1190
1191
1192

•
•
•
•

and counselling), as applicable;
Prescription/ADD order management and dispensing;
ADD medication checking and release;
Contracts with suppliers and consignees (pharmacies, residential care settings, patients etc.), as
applicable;
Data protection;
Distribution of ADD medication;
Waste management;Internal quality/GMP and ADD guideline compliance audits.

1193
1194
1195
1196

Clear operating procedures should be available for all critical aspects of the ADD process and formaintenance and cleaning of the premises and all equipment. An inventory of valid documents within thequality management system should be maintained.

1197
1198
1199
1200

C. Records and Retention of Documents: Records provide evidence of various actions in compliance with
instructions, e.g. activities, events, investigations, and a history of each ADD dispensed medication including
its distribution. Records include any raw data or photographs.

1201
1202
1203
1204
1205
1206
1207
1208
1209
1210
1211
1212
1213
1214
1215
1216
1217
1218
1219
1220

The ADD site should maintain the following records:• A copy of ADD prescriptions/orders (or the original if required by national legislation);• Training records, detailing the policies and procedures that staff are trained in;• Records relating to medicinal products and, as applicable, other materials and products, including delivery
documentation and medicinal product suitability assessments;• Records/logbooks for critical equipment and systems, including records of equipment/system set up,
any use of an area, equipment/method used, environmental conditions, validations, calibrations andmaintenance operations;• Process records including deblistering, storage and ADD;
• Checking and release records;• Records of every ADD medicine dispensed, based on an assigned batch number;• Cleaning records, including details of the particulars cleaned;• Records of procedural deviations, including the rationale for the deviation and the conclusions regarding
impact on the quality, safety or efficacy of the final product or patient safety;• Error records, including details of corrective and preventative actions;• Distribution records, including details of the distribution of each ADD patient’s medication;• Records of self-inspections and external audits, including all observations made and, whereapplicable, proposals for corrective measures. Statements on the corrective and preventative actions
subsequently taken should also be recorded.

1221
1222
1223

All records should be dated and include details of the personnel involved. Patient data should be handled
and maintained with special care to avoid any misuse of the data by unauthorised persons.

1224
1225

The ADD site, and if applicable the associated pharmacy (or similar), should maintain records of patient

26/09/2016

32

1226
1227
1228
1229

suitability assessments and patient consent. The ADD site, or if applicable the associated pharmacy(depending on the contracts in place), should maintain records of medication therapy reviews andcounselling. Records of contracts with relevant healthcare professionals, e.g. physicians or pharmacists,should be maintained.

1230

1237

Records must be retained in accordance with national regulations or standards. In the absence oflegislation, the following retention periods are recommended:• Instructions, including procedures, and specifications: at least five years after they have beensuperseded;• All records related to medicinal products used in the ADD processes: at least one year after expiry dateof the medicinal product/starting material used or the longest dated expiry date of the medicinal
product/starting material used in a dispensed dose;1238• All other records: at least five years.

1231
1232
1233
1234
1235
1236

26/09/2016

33

PART TWO: PATIENT CARE ACTIVITES ASSOCIATED WITH THE ADD
PROCESS

1239
1240
1241
1242
1243
1244
1245
1246
1247
1248
1249
1250

In addition to the ADD process meeting the best possible standards, the incorporation of ADD into thepatient care process must also be understood by all of those involved in the patient’s care. In many cases
the patient’s circumstances will require medicines provided both by conventional dispensing and by ADD.
The simultaneous use of both methods will be the responsibility of the pharmacist who provides caredirectly to the patient and, where they differ, will depend upon communication and collaboration with the
ADD responsible pharmacist. Communication and collaboration with the patient and other members of thehealthcare team is also essential. To ensure that patient safety is optimised in these instances, robust
multidisciplinary procedures to review and manage all of the patient’s medicines must be regularly andsystematically undertaken.

1251
1252

13. LEGAL BASIS:

1253

Patient care activities associated with dispensing medication via ADD must be carried out in accordancewith applicable national regulations and standards. If national regulations and standards are not in place,national authorities should consider establishing a legal framework se t t i n g o ut s t a n d a r d s for patientcare activities, in part icular patient care activities associated with ADD. National guidelines or standards
to facilitate compliance with relevant legislation are recommended.

1254
1255
1256
1257
1258
1259

14. ADD PRESCRIPTION/ORDER AND RESPONSIBILITY FOR PATIENT CARE:

1260

A. ADD Prescription/Order: ADD is carried out in various settings in Europe. ADD medication is preparedin manufacturers, companies and large and small scale hospital and community pharmacies and suppliedin ambulatory and in-patient short and long term care.6
An order/request for medication to be dispensed via ADD can be made by:• the treating physician (health professional with prescribing authority), or• the patient/carer, or• a care institution for a patient who has been prescribed the medication.

1261
1262
1263
1264
1265
1266
1267
1268
1269
1270
1271
1272
1273
1274
1275
1276

The treating physician can request that a patient’s prescribed medication be dispensed via ADD. This should
occur following a patient suitability assessment involving all members of the healthcare team and thepatient/carer. Alternatively, the medical prescription(s) may be transcribed into an ADD order, via a
medication plan upon the request of the patient or a care institution on the basis of a patient suitability
assessment. The medication plan forming the basis of an ADD order should be based on a valid prescription
by a physician or other authorised healthcare professional with access to patient medical records.
Additionally, pharmacists may decide ADD is the most suitable method of providing medication to certain
patients on the basis of a patient suitability assessment conducted in consultation with the treating
physician and the patient/carer.

1277

6

Refer to Section 3.C Setting.

26/09/2016

34

1278
1279
1280
1281
1282
1283
1284

Not all of these mechanisms of requesting ADD medicines are permitted in all European countries. It is
recommended that national authorities determine how prescriptions/ADD requests should bereceived/managed and, if applicable, how prescriptions/orders should be transcribed into a medication
plan prior to forwarding an order to the ADD site. The original prescription or an authorised copy of theprescription should be supplied to the ADD site where more than one entity is involved in the supply. Itshould detail the intention of the prescriber/healthcare team to have the patient’s medication dispensed
via ADD.

1285
1286
1287
1288

B. Responsibility for Patient Care: Responsibility must be assigned in accordance with national regulations
and standards. However, in many countries these responsibilities haven't been fully clarified; clarity
regarding where responsibility for patient care lies is necessary.

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To enable the ongoing review of an ADD patient’s medication therapy, assessment of the patient’s suitability
and the provision of the correct information and appropriate counselling, it is recommended that there isconsistency in the responsibility for patient care. Patients should always receive their medication from thesame pharmacy and should be managed by a healthcare team, which involves the same medical practitioner(or team of medical practitioners) and pharmacist (or pharmacy) for each dispensing, review andassessment.

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Because ADD occurs in various settings in different European countries13, the patient care aspects of the
ADD process may be carried out by pharmacists employed by the ADD site or by an associated dispensing
pharmacy or similar.

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One Entity: Where ADD and supply of medication to a patient/carer occurs in one entity, for example a
pharmacy:• The pharmacist, in particular the responsible pharmacist, at that entity is responsible for the ADD
process and the quality of the resulting medication, for example assessing the suitability of a
medicine for inclusion in ADD.
• The pharmacist is also responsible for patient care, including:o patient suitability assessments,o ensuring patient consent has been obtained,oothe review of medication therapy, andthe provision of patient information and counselling.

Two Entities: Where the ADD service and supply of medication to the patient and/or the patient careservices are provided by two entities, such as a company, manufacturer or pharmacy that supplies ADD
medicines to a pharmacy or directly to patients, pharmacists at the ADD site and at the associatedpharmacy (or similar) bear different responsibilities for patient care:• Pharmacists at the ADD site are responsible for the ADD process and medication;• Pharmacists at the ADD site and/or at the associated pharmacy may have responsibility for patientcare. This varies depending on the country of operation. In some countries the associatedcommunity or hospital pharmacy is responsible for most or all non-ADD site specific activities.

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Where the ADD service and supply of medication to the patient and/or patient care services are provided
by two entities, unless responsibilities have been decided by national legislation or standards,
responsibilities for the different elements of patient care are established and documented in a service
provision contract. It is important that the contract outlines the patient care responsibilities of each entity.

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C. Healthcare Team: An ADD healthcare team should be established to ensure the patient-centric care of
ADD patients. The team has responsibility for patient care and assessing the appropriateness of the use of
ADD for each patient. This team should include the prescriber, who has knowledge of the patient’s medical
and care status and access to the patient’s medical records, and the pharmacist, with their medicinal
product knowledge and responsibility for reviewing prescriptions for therapeutic appropriateness andcounselling. Other healthcare professionals, e.g. nurses where patients are in a care setting, and the patient
themselves, are also integral members of the team. Patients can provide valuable information on theirindividual circumstances and any barriers to their medication adherence. Information systems should
enable the sharing of all relevant information between the members of the healthcare team.

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Unless responsibilities of each member of the healthcare team have been decided by national legislation or
standards, responsibilities for the different elements of patient care and the roles of different members of
the healthcare team should be clearly established within each team.

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D. Education: Health professionals caring for ADD patients should ensure their ADD health literacy ismaintained and improved. Education about the ADD process and its place in the provision of medicines
to patients is required for prescribers, nurses and pharmacists so that health care teams may function
effectively and safely when providing care to patients receiving ADD medicines. It is recommended that
ADD education is included in relevant health professional’s undergraduate training and that healthprofessionals engage in continuing professional development and postgraduate education relevant totheir role in the ADD process and associated care of patients.

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15. PATIENT SUITABILITY:

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A. General: Dose dispensing systems do not provide benefits for all patients; therefore there should be a
documented assessment of a patient’s suitability to have medicinal products supplied via ADD.

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ADD dispensed medicines should only be supplied to patients on the basis of an assessment of an individual
patient’s suitability by the healthcare team, concluding that ADD is the best way to meet the patient’s
needs. The advantages of supplying medicinal products via ADD need to be balanced against thedisadvantages. Advantages can include increased adherence and disadvantages can include the reduced
involvement of patients in the management of their medication, and risks associated with the manipulationof medicines as part of the ADD process.

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These systems are suitable for use by patients who are willing to take their medication and who possess
the visual acuity, dexterity and cognitive skills required to use the system. They are also suitable for
confused patients who are managed by a carer. They are unsuitable for use by those whose medication
regimen is unstable and subject to frequent changes.

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Prior to the provision of a dose dispensed system to a patient, alternative adherence supports should beconsidered, including:• Simplification or tailoring of the medication regimen, e.g. removing unnecessary medication, altering
times of administration or using combination products;• Reminder charts;• Visual aids, e.g. large font information sheets, magnifying glasses, pictograms;• Memory aids, e.g. software applications, timed alarms or calls from a relative;• Involvement of a carer or relative to help administer medication.

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Medicine review may identify further barriers to adherence which may be overcome by interventions suchas a change in formulation or the use of non child-resistant closures on containers.

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B. Suitability Assessments: Prior to deciding to supply a patient’s medicine via ADD, a documented
assessment of a patient’s suitability should occur. This assessment should consider both patient-specificand medication-specific issues and should, as a minimum, address:• The ability of the patient to manage their medication and adhere to their medication regime;• The likelihood that alternative adherence supports will improve adherence and the likelihood that adose dispensing system will improve adherence;• Patients’ preference for a dose dispensing system or conventional dispensing;• Patients’ health status and circumstances, e.g. patients with literacy problems or memory problems;• The ability of the patient to use conventional dispensing systems and their ability to use ADD systems,
e.g. patients with physical disabilities;• The impact of the loss of independent decision making and decrease in patients’ involvement in the
management of their medical condition and therapy;• The impact of the loss of information and patient safety features e.g. information in braille andopening devices;• The setting in which the patient is located, e.g. dose-dispensed medicinal products are not usuallynecessary if a healthcare professional is administering the medication;• The possibility of confusion if not all of the patient’s medications are suitable for inclusion in a dose
dispensing system, e.g. injections, suppositories, effervescent tablets, ‘as required’ medication or
medication for acute conditions. Note: there are some ADD systems that can contain non-oral
formulations. The type of ADD system and its capabilities can also form part of the assessment.

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It should not be assumed that all patients in a particular setting, e.g. hospital or long-term institutional careare suitable for ADD. Assessment tools for determining suitability, e.g. a grading system for different typesof patients and/or an assessment of the personnel responsible for medication administration, could form
part of the patient suitability assessment. Decisions on hospital or institutional policy regarding patient
suitability assessments and the use of ADD should involve all members of the healthcare team and may, if
considered appropriate, also involve relevant managers.

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C. ADD Suitability: Dose-dispensing systems are not a suitable intervention:• Where other simple adherence supports (as outlined above) will achieve the same levels ofadherence;
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•

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•

For intentional non-adherence: if a patient doesn’t want to take their medication, discussing andaddressing the reason for non-adherence is the correct approach;For convenience purposes: the decision to supply medicinal products in an ADD system should
be based on patient need and appropriateness rather than the requirements of any
establishment or institution. All patients on similar medication or in the same care setting or
institution should not automatically receive their medicines via ADD.

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Dose dispensing systems are a suitable intervention:• Where, following a documented assessment, it has been decided that provision of medication via
ADD will bring benefits to the patient and it is likely that adherence will be achieved. In particular
this applies where other adherence supports have been tried and, despite the best intention of thepatient, failed;• For patients who are willing to take their medication and have the visual acuity, dexterity andcognitive skills required to use the system;• For patients on a lot of medication, who find it difficult to manage taking the right medicines at theright times;• For confused patients if they are managed by a carer. Many patients in institutions fall into thiscategory. Adequate training of carers providing medication to patients via ADD is essential.

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D. Suitability Reassessments and Risk of No Assessments: Periodic reassessment of the suitability of ADD
medicines for a patient is an important part of the process. Reassessment should occur at appropriate
intervals for the individual patient.
They should occur:• When the patient’s medication changes; when medication is added, stopped or the dose or
frequency changes;• When the patient’s health status or circumstances change; if a new condition is diagnosed, if there
is significant deterioration in a condition or if the patient has moved into residential care;• As a minimum, at yearly intervals, where there is no change that warrants earlier reassessment.

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Risks associated with a lack of patient suitability assessments are:
• Patients not taking their medication or only taking some of their medicationo due to intentional non-adherence, oro because of reduced involvement in their medication management;• The introduction of the inherent risks of manipulating medicines via ADD without a benefit: risk
ratio assessment.
ADD medicines should only be provided where the benefit: risk ratio is favourable and this has been
determined by a patient suitability assessment.

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Records of all initial assessments and re-assessments should be maintained by all members of theassessment team and a copy provided to the patient/carer.

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16. PATIENT CONSENT:

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Prior to supplying a patient’s medication via ADD, every patient (or person authorised to take decisions on
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the patient's behalf) should be asked if they would prefer to receive their medicinal products in aconventional manner or via ADD.

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Voluntary informed consent should be obtained. Adequate information on the benefits and risks ofreceiving medicines via ADD should be included on the consent form. I n f o r m e d c o n s e n t s h o u l d b e
documented for each patient receiving ADD medicines. Consent to any associated data transfer should
also be documented.

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17. REVIEW OF MEDICATION THERAPY, COUNSELLING, INFORMATION PROVISION AND
EDUCATION:
A. Review of a Patient’s Medication Therapy: The healthcare team should carry out regular reviews toassess the pharmaceutical and therapeutic appropriateness of patients’ medication therapy. A review
involves considering each medicinal product individually and collectively, including
screening for any potential therapy problems which may arise out of the use of the medicinal products.
Both general and ADD specific patient care elements are to be considered as part of the review.

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Important elements of a review include, but are not limited to:• The requirement and indication for each medication;• Therapeutic duplication;• Interactions with other medicinal products (including interactions with non-prescription medicinal
products, herbal products or foods);• Incorrect dosage or duration of treatment;• Allergies;• Previous adverse reactions;• Clinical abuse and/or misuse.
The review should also identify if patients are taking medicines that may not be suitable for inclusion in adose-dispensing system, e.g. effervescent tablets.

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Review of a patient’s medication by the relevant healthcare professional (prescriber or pharmacist) should
occur each time a medication is prescribed and dispensed.

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More detailed, structured medication reviews should occur at an appropriate frequency. These should
examine a patient’s medication with the objective of reaching an agreement about treatment between theprescriber, pharmacist and patient. Their aim is to optimise the impact of medicines and minimise thenumber of patient related problems. The patient’s healthcare team should participate in theinterdisciplinary review of each patient’s medication. The patient should also be involved to ensure they
are an active participant in their care, to identify any patient-specific issues, and to empower the patient.
Patients’ adherence to their medication regime should form part of the review. Records of participation inthese reviews should be retained.

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Risks associated with no regular structured medication reviews include:• The continuation of medication that is no longer needed or delay in including a new medicine in
the system;
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•

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•
•

Reduction of the frequency with which changes to medication are made: the patient's healthstatus may not be reassessed if a patient is categorised as a long term ADD medicine user andpatients may remain on unnecessary medication;
Inclusion of a new medicine without considering all necessary factors;
Lack of patient and carer feedback on whether the system is helping or hindering their adherence.

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In addition, regular communications/meetings as a forum to discuss patients’ care and treatment and any
issues which the pharmacist or medical practitioner, in their professional judgment, deems appropriate
are recommended. Individual multidisciplinary patient care plans and/or patient healthcare records canalso be beneficial. The primary aim should be to ensure patients receive an appropriate standard of care.

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B. Patient Information and Counselling: Patients should receive comprehensive instructions andcounselling. Patients should be adequately introduced to ADD, particularly patients switched fromconventionally dispensed medicine to ADD, and should be provided with information on why the system issuitable for them. The pharmacist should ensure at each supply that the patient has sufficient information
and advice for the proper use and storage of the ADD medication.
As with all medicinal products supplied, it is important that prescribers and pharmacists offer counsellingto the patient, or their carer, on any matters relating to ADD medicines and medicines supplied in analternative manner that they, in the exercise of their professional judgment, deem significant. This may
include but is not limited to:• The identification of medicinal products supplied via ADD. Pictures of medication should be provided toaid medication identification where more than one medicine is packed in a container;• Explanations of any changes since the last dispensing;• Storage instructions, e.g. protecting the ADD medication from light and the safe storage of the ADD
containers ‘out of the reach of children’;• The therapeutic benefit which may be expected from the use of medicinal products supplied via ADD
and in an alternative manner;• Any special directions and precautions;• Any severe side-effects, interactions or contraindications;• Any other matters which may be included or referred to in the Summary of Product Characteristics forthe medicinal product concerned.

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It is important to ensure that patients and their carers are provided with or have access to the current
patient information leaflets and any relevant information on the authorised packaging of the medicinal
products supplied. ADD sites should also ensure that the font and labelling on pouches is clear, legible andof an appropriate size for an individual patient’s circumstances.

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Information on additional adherence supports that may be used in conjunction with the ADD systemshould be provided if such aids are available, for example:• If a dose is missed some ADD devices provide signals or trigger a message to the patient/carer;• Medication applications may be used for tracking medication administration or providing patient
information leaflets.
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C. Patient Education: ADD should be accompanied by concomitant programmes for improving patients’
health literacy, education and empowerment through expert-patient programmes that develop selfefficacy and adherence. ADD service providers, other health professionals and patient organisations
should provide information to patients.

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18. DOCUMENTATION AND RECORDS:

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There should be documents (policies, procedures, specifications) and records in place for the following
patient care processes:• Obtaining informed patient consent;• Patient suitability assessments and reassessments;• Prescription/ADD order management;• Medication therapy review (individual and multidisciplinary);• The provision of patient information leaflets and information on medication changes;• Additional counselling;• Data protection;• Contracts and interactions/meetings with relevant healthcare professionals, e.g. physicians or otherpharmacists;• Pharmacovigilance.

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Records should be maintained at the site or sites responsible for a particular activity. Where two entities
are involved some records should be maintained at both entities, for example, prescriptions and contracts.
All records should be maintained for five years. Copies of relevant records including patient suitability
assessments, medication reviews and patient consents should be provided to patients.

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References:

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1.

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EJHP Practice 2006; 12: 50-51.
2. The Association of Finnish Pharmacies - Annual Review: Medicines in pre-packed doses; 2003.
http://www.apteekkariliitto.fi/media/pdf/annual_report_2003.pdf
3. Larsson A, Åkerlund M: ApoDos: the Swedish model of multi-dose. EJHP Pract 2007; 13:51.
4. Danish Health and Medicines Authority: Dose dispensing;https://laegemiddelstyrelsen.dk/en/pharmacies/pharmacies/dose-dispensing#
5. Schwarz HO, Brodowy BA. Implementation and evaluation of an automated dose dispensing system.
Am J Hosp Pharm. 1995; 52: 823-828.
6. Fanikos J, Erickson A, Munz KE, Sanborn MD, Ludwig BC, Van Hassel T. Observations on the use of
ready-to-use and point-of-care activated parenteral products in automated dispensing cabinets in US
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7. Barker KN. Ensuring safety in the use of automated medication dispensing systems. Am J Hosp
Pharm1995; 52: 2445-2447.
8. Herborg H, Haugbølle LS, Lee A. Automated dose dispensing in Danish primary health care - atechnology under construction. Pharm Pract 2008; 6(2): 103-112.
9. Wekre LJ, Bakken K, Garåsen H, Grimsmo A. GPs’ prescription routines and cooperation with other
healthcare personnel before and after implementation of multi-dose drug dispensing. Scand J Public
Health 2012; 40: 523–530.
10. Gilmartin JF, Hussainy SY, Marriott JL. Medicines in Australian nursing homes: a cross-sectional
observational study of the accuracy and suitability of re-packing medicines in pharmacy-supplied dose
administration aids. Res Social Adm Pharm 2013; 9(6): 876-883.
11. Bergkvist A, Midlöv P, Höglund P, Larsson L, Bondesson A, Eriksson T. Improved quality in the hospitaldischarge summary reduces medication errors - LIMM: Landskrona Integrated Medicines Management.
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14. Wekre LJ, Spigset O, Sletvold O, Sund JK, Grimsmo A. Multi-dose drug dispensing and discrepancies
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16. Balka E, Kahnamoui N, Nutland K: Who is in charge of patient safety? Work practice, work processes
and utopian views of automatic drug dispensing systems. Int J Med Inform 2007; 76: 48–57.
17. Johnell K, Fastbom J. Multi-dose drug dispensing and inappropriate drug use: a nationwide registerbased study of over 700,000 elderly. Scand J Prim Health Care 2008; 26: 86–91.
18. Sjöberg C, Edward C, Fastbom J et al. Association between multi-dose drug dispensing and quality ofdrug treatment: a register-based study. PLoS One 2011; 6: e26574.
19. Sjöberg C, Ohlsson H, Wallerstedt SM. Association between multi-dose drug dispensing and drug
treatment changes. Eur J Clin Pharmacol 2012; 68: 1095–1101.
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medication understanding, and medication stockpiles. Res Social Adm Pharm 2007; 3: 265–284.

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21. Kwint H-F, Slk G, Faber A, Gussekloo J, Bouvy ML. Medication adherence and knowledge of older
patients with and without multidose drug dispensing. Age and Ageing 2013; 42(5): 620-626.
22. Sinnemäki J, Sihvo S, Isojärvi J, Blom M, Airaksinen M, Mäntylä A. Automated dose dispensing service
for primary healthcare patients: a systematic review. Syst Rev 2013; 2: 1.
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people. Age and Ageing 2013; 42(5): 556-558.
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