2015
DRAFT POSITION STATEMENT – V2
Safer design and use of vaccines
BACKGROUND
Immunization is widely recognized as one of the most effective public health intervention ever
introduced worldwide. According to the World Health Organization (WHO), immunization avoids
between 2 and 3 million deaths per year from vaccine preventable diseases(1). However, errors with
vaccines can result in an unintended and unrecognized source of vulnerability. While the immediate
impact of a vaccine-related error on a patient may not be serious, such errors may render the vaccine
ineffective or reduce its effectiveness, leaving patients unprotected against serious diseases.
The evidence of vaccination errors, specific medication errors related to the use of vaccines, is well
established by national reporting programmes such as: the US Vaccine Adverse Event Reporting
System (VAERS)(2-5), jointly administered by the Centers for Disease Control and Prevention (CDC) and
the US Food and Drug Administration (FDA); the ISMP National Vaccine Errors Reporting Program
(ISMP VERP)(6,7), in partnership with the California Department of Public Health; the Institute for Safe
Medication Practices Canada (ISMP Canada)(8); the UK Health Protection Agency (HPA)(9); the England
and Wales National Reporting and Learning System (NRLS)(10,11). Most of these incidents are reported
in developed countries, but the type of errors that occur can be expected to be similar to those around
the worlda.
If these various assessments were not sufficient to demonstrate the persistence of vaccine-related
errors, the deaths in September, 2014 of 15 Syrian children among 75 vaccinated from a measles
vaccine reconstituted with atracurium instead of the diluent remind us that vaccine diluent mix-ups can
be tragic and have a devastating effect on immunization and health efforts(12). The Institute for Safe
Medication Practices (ISMP) remembered several similar incidents of accidental reconstitution of
vaccine with neuromuscular blockers that have previously been reported: in the United States of
America (at least one death among several harmed patients); in Taiwan (a permanent injury and one
death among 7 infants developing respiratory distress); in Mexico (one death among 14 patients
presenting hypotonia, cyanosis, and dyspnea); in Kenya (6 infants exposed); in Lesotho (one death
among 5 neonates)(13). Similar mix-ups between vaccines or diluents and insulin have led to 21 children
deaths in 1997 and continue to occur (1,14).
During its annual meeting held in Singapore on 20-21 October 2014, the International Medication
Safety Network (IMSN) convened a workshop on vaccine errors, focusing on safer design of labelling
and packaging of vaccines.
Vaccine related errors may occur at all stages of the medication use process: prescribing, dispensing,
preparing, administering, follow-up and planning with a particular emphasis to scheduling and
documenting the patient held record (PHR):
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Wrong patient errors, especially sibling confusion
Wrong time errors: omissions, delay, extra dose
Wrong vaccine: incorrect vaccine administered
Wrong preparation / Wrong diluent
Wrong dose: incorrect dose (under dose, overdose), extra dose
Wrong dosage form
Wrong expiry: expired vaccine, deteriorated product
Wrong administration technique
Wrong route of administration
a
Eventually, update from WHO Vigibase for a picture at a global level (see David Cousins’ presentations or ask
a request to Shanti Pal or a password for VigiLyze) ?
DRAFT IMSN Position Statement – V2 | Safer design and use of vaccines
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Many causes of errors and contributing factors are expanding in a context of an increasing number of
vaccines, more complex vaccines (combinations of multiple components and valences), ever changing
vaccination recommendations and schedules, and vaccines shortages that disturb immunization plans:
 Confusion due to unclear brand names; similar names; unclear or similar abbreviations
 Confusion due to similar and ambiguous packaging: insufficient differentiation among
products from one manufacturer, lack of consistency of packaging levels
 Confusion due to similar and ambiguous labeling: illegible labels due to small font and
label sizes; on curved items such as vials or ampoules, full pieces of information cannot be
seen in one view; use of multi-language on packaging; Information placement; multidose
not stating the number of doses available nor the volume per dose
 Confusion between multi-dose and single dose vaccines
 Age-related contributing factors: age-dependent formulations of the same vaccine;
confusion between pediatric and adult formulations; unfamiliarity with dosing and timing
of vaccines based on the patient’s age; failure to verify the patient’s age prior to
administration
 Combined or multicomponent vaccines: lack of identification and use of the appropriate
diluent; misunderstanding of the reconstitution of a vial with a prefilled syringe; giving just
one component instead of the intended combination vaccine; use of an unintended diluent
instead of the specific diluent
 Complex vaccination schedules and frequently changing vaccination recommendations
 Vaccine shortages leading to the use of different combined vaccines then intended and
modification of the vaccination schedules
 Storage conditions: temperature lower or greater as recommended; products stored near
each other (not only vaccines, but also neuromuscular blocking agents, insulin, etc.); unclear
expression of expiry date; water damage (from freeze packs) degrading labels
 Overcrowded SPC: hidden information related to the validity of reconstituted vaccines
 Documentation error: incorrect notes and computer record (Patient Held Record: PHR);
failure to check the vaccine record prior to administration
 Attendance of several children in the same office for immunizations together: distraction
due to crying children, etc.
POSITION STATEMENT
The International Medication Safety Network recommends the following steps as part of a
comprehensive, worldwide solution to the problem of unsafe design and use of vaccines.
1.
2.
3.
4.
Labelling of vaccines should: use larger fonts for better readability; adopt the WHO VPPAG
expiration dates standard (MM-YYYY, meaning that the product expires at the end of the month);
provide peel-off labels; and clearly differentiate pediatric and adult formulations.
Packaging of vaccines should minimize the need to prepare individual doses: provide unit dose
according to the mode of administration (e.g., prefilled syringes for parenteral); if still used,
redesign the vaccines package in vials that accommodate larger labels.
A particular attention should be paid to the packaging and the labelling of vaccines and diluents
or 2 components vaccines:
a. Packaging that forces proper mixing of a diluent or two component vaccines (i.e. dual
chambered vial) should be preferred; if not feasible, the 2 vials of vaccines and diluents or
two-component vaccines should be packaged together.
b. All labels of vaccine products that require reconstitution prior to administration should provide
clear instructions for mixing vaccine components, including: directions for use and warnings
to administer the contents of both vials together on the front carton label and vials—
eventually on their caps; a bold statement on the diluent, if provided, indicating that it is
only a diluent, not the actual product; GTIN or national code numbers and barcodes on
each vaccine component and diluent.
Healthcare authorities and medicines regulators should promote safer labelling and packaging of
vaccines and make available recommendations to healthcare providers for safer vaccination
practices especially regarding healthcare professional’s competencies, vaccines selection, storage,
preparation and administration, and patient information and vaccination documentation.
DRAFT IMSN Position Statement – V2 | Safer design and use of vaccines
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Recommended Specific Actions
Immunization experts, pharmaceutical companies, technology vendors, professional organizations, and
regulatory/standard-setting organizations, can help improve vaccine safety and efficacy by taking
actions to vastly reduce the risk of vaccine-related errors.
Globally, several WHO recommendations already exist, addressing in particular:
 Reporting and learning from adverse events following immunizations (AEFI) under the
guidance of the WHO Global Advisory Committee on Vaccine Safety (GACVS): the AEFI
surveillance system encompasses reporting, investigation, causality assessment and
classification of cause-specific AEFI, including immunization error-related reactions defined
as AEFI that are caused by inappropriate vaccine handling, prescribing or administration
and thus, by its nature, are preventable (1,15);
 Presentation and packaging of new vaccines for use by public-sector programmes in
developing countries, recommendations for vaccine producers and developers generated
by the WHO Vaccine Presentation and Packaging Advisory Group (VPPAG)(16), especially
focusing on some safety concerns as shown by following quotations:
o “Provide vaccines, whenever possible, in “ready-to-use” presentations that do not
require the mixing of components”
o “Provide vaccines in formats to minimise the (1) number of steps and (2) potential
for error during preparation and administration”
o “Vaccines packaged in prefilled injection systems should have both space-saving and
auto-disabling features”
o “To ensure that all components are available together at the point of delivery, it is
possible to keep multiple components of a vaccine together throughout the product’s
entire distribution process or during segments of the distribution process (physical
bundling of multi-component vaccines)”
o “It is recommended that secondary carton materials, including printing and attached
labels, be resistant to long-term exposure to condensation”
o “Primary container labels:
Minimum requirements could include: Product name, manufacturer, expiry date,
batch/lot number, dose volume, and number of doses in the container. Storage
conditions and method of administration might also be considered.
Use of standard, generic names could create consistency and improve correct product
use. Brand names could also be included.
The format of the expiry date: an all numeric format MM-YYYY should be the
standard, meaning that the product expires at the end of the month.
A minimum font size and type should be required for label legibility.”
o “Include a label containing a heat-sensitive material that is placed on a primary
vaccine container to register cumulative heat exposure over time (VVM vaccine vial
monitors) on all vaccines, as recommended by the World Health Organization
(WHO) and the United Nations Children’s Fund (UNICEF)”
o “It is recommended that secondary and tertiary cartons be labelled on at least two
opposing faces, with a preference for three opposing faces, following the design
principles set out in Guidelines for the Labelling of Vaccines: Proposed Amendments
to the TRS 822 Document & Requirements for Pre-Qualified Products.”
o “Bar code data should include the Global Trade Item Number (GTIN), lot number,
and expiry date”
Taking in account these global recommendations, IMSN welcome some progress in vaccine safety but
wishes to go beyond in order to foster safer vaccination practices. IMSN prepared recommendations
on the basis of the work previously done by members, especially the ISMP(17,1). The following IMSN
recommendations were submitted for discussion and adopted during its meeting held in Cartagena on
30 September - 1 October 2015.
DRAFT IMSN Position Statement – V2 | Safer design and use of vaccines
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Recommendations for the pharmaceutical industry
Manufacturers of vaccine products are strongly encouraged to revise the packaging and labeling of
vaccine products as specified, with a particular attention on vaccines and diluents or two-component
vaccines. An international summit on vaccine safety should be held to discuss the feasibility of the
following IMSN recommendations:
a. Package vaccines in unit dose, prefilled syringes appropriate to the mode of administration (e.g.,
parenteral vs. oral) to minimize the need to prepare individual doses.
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Redesign the vaccines package in vials that accommodate larger labels to reduce label
crowding.
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Whenever feasible, consider packaging that forces proper mixing of a diluent or two
component vaccines (i.e. dual chambered vial or syringe).
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Whenever possible given storage requirements, the 2 vials of vaccines and diluents or
two-component vaccines should be packaged together in a way that facilitates selection of
both vials at the same time but allows separation if necessary to prepare the vaccine for
administration.
b. Improve the labeling of vaccines by:
c.
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displaying expiration dates in a standard, straight-forward way that can be understood
by all.
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clearly differentiating pediatric and adult formulations.
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using larger fonts to make labels more readable.
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making peel-off labels available to promote immediate labeling of prepared syringes
and accurate documentation of administration.
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providing clear instructions for mixing vaccine components on all labels of vaccine products
that require reconstitution prior to administration: directions for use and warnings to
administer the contents of both vials together on the front carton label and vials—
eventually on their caps.
The diluent, if provided, should include a bold statement indicating that it is only a diluent,
not the actual product.
Unique GTIN or national code numbers and barcodes should be provided on each vaccine
component and diluent.
Conduct usability testing with vaccine users to test labels, packages and preparation process for
safety, convenience, clarity and effectiveness.
Practice recommendations for the healthcare providers
Preventing vaccine-related errors in practice means to establish safety controls and procedures at
different stages of the vaccination process:
a. Healthcare professionals and assistants who immunize patients or handle vaccines (procurement,
inventory management, preparation for patients) to undergo periodic training and demonstrate
competencies related to the types of vaccines being administered and understanding of the
differences between two-component vaccines and vaccines packaged with specific diluents.
b. Safe selection of vaccines:
Purchase vaccine in the safest packaging (i.e. prefilled syringes, oral applicator, differing agespecific formulations of the same vaccine from different manufacturers to help distinguish them)
Use full names or standard abbreviations, keeping in mind that errors are still possible, even when
using standard vaccine abbreviations, given abbreviation similarities (e.g., DT, Td, DTaP, Tdap) or
difficulty recalling the correct abbreviations.
c.
Safe storage of vaccines:
Maintain cold storage and monitor the temperature of vaccine storage units and take immediate
action in response to temperature excursions.
DRAFT IMSN Position Statement – V2 | Safer design and use of vaccines
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Separate vaccines in all storage areas, and affix auxiliary labels to the vaccines and/or storage
containers, particularly pediatric and adult formulations of vaccines, vaccines with similar names or
abbreviations, or overlapping component(s), newborn vaccines (HepB) and mother’s medication
supplies. If more than one vaccine type must be administered, keep the vaccines separate (e.g.,
separate trays; separate sections of trays; separate vaccine administration stations) when feasible.
Distinguish the most critical information on vaccine containers by circling the information,
highlighting the information, or using auxiliary flag-type labels without obscuring existing label
information.
Keep vaccines with diluents (if required) by using a rubber band or placing them together in a
sealable plastic bag.
d. Safe information on vaccines and immunization:
Make immunization schedules available, including electronically for healthcare consumers, with
smart phone access.
Establish standard order sets or protocols for frequently administered vaccines including:
1) criteria for screening patients to determine the need for vaccination, indications,
contraindications, and precautions,
2) directions for administering the vaccine, including any special procedures required to enhance
safety (e.g., involving the patient/parent in the checking process),
3) information regarding any required follow-up doses,
4) details regarding where to document vaccine administration, and
5) an emergency protocol to follow if the patient develops an adverse reaction.
Provide patients or parents/caregivers with written information about vaccines before vaccination.
e. Safe vaccination process:
A standard process for vaccine handling and documentation is needed for the medical office, clinic
and pharmacy (where pharmacist are involved in the vaccination process).
If multiple children, adults, or an adult and child are being seen at the same time for vaccinations
in the same immediate vicinity, structure the appointment to vaccinate one patient at a time.
Moving siblings to separate treatment rooms when possible is one way to approach the problem. If
more than one patient remains together, bring only one patient’s vaccines into the treatment area
at a time, labeled with the vaccine name and intended patient’s name on each container.
Avoid drawing vaccines into syringes in advance of administration and, if any, label all vaccines
prepared in syringes.
Involve the patient or parent(s)/caregiver(s) in a vaccine verification process by:
1) verifying the patient’s age by asking the birth date (if the patient is available), the patient’s
current immunization status by checking the patient’s health record and vaccination
and documenting the vaccine name, formulation (pediatric or adult, if applicable), lot number,
NDC, and expiration date(of each vaccine component if necessary) on the patient’s vaccine record
prior to preparation/administration of the vaccine,
2) bringing the vial and syringe or the prefilled syringe along with the immunization record into the
exam room,
3) asking the patient or parent to simultaneously verify and sign on the immunization record while
a healthcare provider reads the information on the label aloud,
4) asking the patient or parent if the vaccine verified is what they expected to be administered
(based on an immunization schedule provided to the patient or parent previously), and verify the
intended patient’s identity using two unique identifiers (e.g., name and birth date),
5) preparing and administering the vaccine immediately after verification, and
6) documenting the vaccine on the patient’s medical record (providing an opportunity for a
double-check).
International Medication Safety Network
The International Medication Safety Network (IMSN) is an international network of safe medication
practice centers established with the aim of improving patient safety. This is achieved by operating
medication error reporting programmes and producing guidance to minimize preventable harms from
medicine use in practice. IMSN promotes safer medication practice to improve patient safety
internationally.
For more information
www.intmedsafe.net/contents/AboutIMSN.aspx
DRAFT IMSN Position Statement – V2 | Safer design and use of vaccines
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References
1.
World Health Organization "Global manual on surveillance of adverse events following immunization"
2014; 128 pages.
2.
Varricchio F "Medication errors reported to the vaccine adverse event reporting system (VAERS)" Vaccine
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3.
Varricchio F et Reed J "Follow-up study of medication errors reported to the vaccine adverse event reporting
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4.
Chang S et coll. "Preventable mix-ups of tuberculin and vaccines: reports to the US Vaccine and Drug Safety
Reporting Systems" Drug Saf 2008 ; 31 (11) : 1027-1033.
5.
Hibbs BF et coll. "Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS)
United States, 2000-2013" Vaccine 2015 ; 33 (28) : 3171-3178.
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Institute for Safe Medication Practices (ISMP) "First annual review of data submitted to the ISMP National
Vaccine Errors Reporting Program (VERP)" ISMP Medication Safety Alert! Acute Care 2013; 18 (24): 1-5.
7.
Institute for Safe Medication Practices (ISMP) "Confusion abounds! 2-year summary of the ISMP National
Vaccine Errors Reporting Program (Part I)" ISMP Medication Safety Alert! Acute Care 2014; 19 (24): 1-6.
8.
Institute for Safe Medication Practices Canada (ISMP Canada) "Administration of Product-Specific Diluent
without Medication" ISMP Canada Safety Bulletin 2010; 10 (7): 1-3.
9.
Craig L et coll. "Pragmatic management of programmatic vaccination errors--lessons learnt from incidents in
London" Vaccine 2010 ; 29 (1) : 65-69.
10. Rees P et coll. "Safety incidents in the primary care office setting" Pediatrics 2015; 135 (6) : 1027-1035.
11. Rees P et coll. "Pediatric immunization-related safety incidents in primary care: A mixed methods analysis of
a national database" Vaccine 2015; 33 (32) : 3873-3880.
12. Cousins S "Contaminated vaccine deaths a serious setback for Syria" Lancet 2014 ; 384 (9949) : 1172.
13. Institute for Safe Medication Practices (ISMP) "Tragic vaccine diluent mix-ups in Syria have also happened
here." ISMP Medication Safety Alert! Acute Care 2014; 19 (19): 1-3.
14. Institute for Safe Medication Practices (ISMP) "What else is stored in a refrigerator with influenza vaccine?"
ISMP Medication Safety Alert! Acute Care 2014; 19 (24): 1.
15. World Health Organization "Causality assessment of adverse event following immunization (AEFI): user
manual for the revised WHO classification." WHO/HIS/EMP/QSS. March 2013; 56 pages.
16. WHO Vaccine Presentation and Packaging Advisory Group (VPPAG) "Generic Preferred Product Profile for
Vaccines. Version 2.1 Recommendations" 31 March 2015; 31 pages.
17. Institute for Safe Medication Practices (ISMP) "Recommendations for practitioners and manufacturers to
address system-based causes of vaccine errors" ISMP Medication Safety Alert! Acute Care 2014; 19 (5): 1-5.
18. Institute for Safe Medication Practices (ISMP) "Recommendations for practitioners to prevent vaccine errors.
Part 2: Analysis of ISMP Vaccine Errors Reporting Program (VERP)" ISMP Medication Safety Alert! Acute Care
2015; 20 (6): 1-6.
DRAFT IMSN Position Statement – V2 | Safer design and use of vaccines
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