Vaccine Packaging at the Clinical Interface of Vaccine, Healthcare Worker, and Patient

Vaccines are one of the greatest achievements in public health. A recent economic analysis indicated that vaccination of each US birth cohort with the current childhood immunization schedule prevents approximately 42,000 deaths and 20 million cases of disease, with net savings of nearly $14 billion in direct costs and $69 billion in total societal costs (1).

Brian Lynch

The success of vaccination, particularly in developed nations, has been based on public recognition of their benefits, access to vaccines, and continuing efforts to promote their use as an integral component of health and preventative care.

Philip Song

Despite these successes, opportunities remain to improve vaccination coverage in the US. In 2010, the National Vaccine Plan was revised and updated, setting vaccination goals and strategies aimed to ensure a stable supply of, access to, and better use of recommended vaccines in the US (2). Thus, any way to enhance or improve the systems to help ensure safe and more efficient vaccination should be pursued.

THE EVOLVING VACCINATION SETTING

The vaccination setting in the US is rapidly evolving from its traditional medical home to nontraditional ones, such as retail outlets, schools, and pharmacies. As an example, during the 2010–2011 influenza vaccination campaign, 18.5% of adults received their flu shot in a retail setting (3). Along with the change in the setting is a change in the profile of vaccinators in these new settings, with those individuals possessing different and varying clinical experience and education. Another reality is that the immunization enterprise is facing increasing cost pressures throughout healthcare. Furthermore, all vaccination venues are seeking opportunities to lower the costs of delivering vaccination.

To help ensure consistent, efficient, and cost-effective vaccinations, all means to simplify the vaccination process should be considered. In this light, the vaccine package—which plays an important role at the clinical interface between vaccine, patient, and caregiver—is increasingly viewed as a crucial component of vaccination. Today there are three types of vaccine packages in use: prefills (PFSs), multi-dose vials (MDVs), and single-dose vials (SDVs). Each package has different implications for clinical practice, efficiency and cost, and, potentially, patient outcomes.

EFFICIENCY AND PRACTICE IMPLICATIONS—A CLOSER LOOK

A 2010 time-motion study performed by The Johns Hopkins University Bloomberg School of Public Health demonstrated the safety and workflow advantages of PFSs (4). Investigators observed more than 1500 vaccine injection preparations, and determined time differences and subsequent cost differences associated with the use of PFSs vs. MDVs. They also observed preparation and handling practices.

Investigators found that preparing a dose using MDVs took 37 seconds longer than with PFSs because of the increased number of steps required to prepare a vaccine packaged in a vial. Assuming standard costs for materials and labor, researchers concluded that administration of vaccines via PFSs could save a clinic approximately $1100 per 1000 doses assuming the same price per vaccine dose.

More significantly, PFSs reduce the risks associated with deviation from best practices as established by the US Centers for Disease Control and Prevention (5). For example, researchers observed the following deviations from best practices with MDVs:

• Neglecting to write on a vial the date it was opened

• Not properly sterilizing the rubber stopper before withdrawing vaccine dose

• "Trusting" memory for transcribing lot number

• Predrawing the day before or using leftover predrawn syringes from a previous day

• Predrawn syringes were often left out (not refrigerated) for long periods of time and, in some cases, for a whole day

• Drawing vaccine from multiple vials, especially without checking if the lot numbers were the same (6).

By eliminating the preparation steps required with a vial, a prefilled syringe is simpler and easier to use. Vaccination workflow may be faster and smoother for clinicians and may improve speed of patient throughput.

An additional and important advantage offered by PFSs is that they come from the manufacturer, labeled by the manufacturer. All too often, syringes predrawn from vaccine vials are left unlabeled, or are subject to variable labeling practices, clinic by clinic or perhaps even clinician by clinician. This variability increases the risk of a wrong or improperly stored injectable vaccine being given; dosing errors also increase when vaccine is prepared and labeled by hand (7). Prefilled and prelabeled syringes avoid these errors and omissions, ensure accurate dosing, and offer clinics a ready-to-use, safe, and simple time-saving alternative to predrawing several vaccine syringes in advance.

VARIABILITY IN CLINICAL PRACTICE

Variations from clinical best practices can be influenced by many different factors, including experience, education, and "real-life" clinician scenarios (e.g., multi-tasking, distractions, or work-flow pressure). While the vaccine enterprise in the US is considered safe, there have been case studies that show that errors in preparation and administration can occur.

In 2010, Premier Safety Institute conducted a large study with more than 5000 clinicians to understand the "current injection practice patterns to assist with targeting outreach and education." This study was done in response to "increasing reports of outbreaks in the US involving transmission of Hepatitis B and C to patients associated with unsafe injection practices and breakdowns in basic infection control" (8). For example, an outbreak occurred during the 2007–2008 influenza campaign when a New York physician's office engaged in a practice of drawing six 0.5-mL influenza vaccine doses into a 3-mL syringe and subsequently vaccinated six individuals with the same syringe while only changing the needle (9).

The Premier study revealed that this practice may be more widespread than perhaps anticipated: 0.9% of the clinicians in the survey reported that they change the needle but reuse the syringe on multiple patients. In this same study, 6% of the clinicians also reported using single-dose or single-use vials for more than one patient, and 1.1% reused a syringe to enter a multi-dose vial and then saved that vial for use on another patient (8).

CDC guidelines recommend that healthcare workers use single-dose vials, syringes, and needles only once, which precludes their use in more than one patient. The study authors wrote, "Our findings provide evidence that healthcare professionals continue to engage in unsafe injection practices, which represent an ongoing threat to patient safety in the United States and are devastating to all those patients who are impacted." (8)

THE IMPACT OF VACCINE PACKAGING AT THE USER INTERFACE

In a recent article in the American Journal of Infection Control the authors stated, "Although there is a clear need for more education, this may not necessarily eliminate all unsafe practices. Adopting principle from human factors engineering, we must consider redesigning devices, equipment, and processes to reduce or eliminate risk of bloodborne pathogen transmission" (8). This statement is consistent with FDA's increasing requirements around the integration of Human Factors Engineering (HFE) and device design. HFE is "the science and the methods used to make devices easier and safer to use....helping to improve human performance and reduce the risks associated with use" (10).

To better understand the user interface of clinician and various vaccine packages, and the associated potential for errors, a comprehensive study was commissioned by BD and conducted in 2011 by Interface Analysis Associates (11). The researchers outlined the process of vaccine preparation from storage through disposal for the three vaccine package types, and then developed a list of all potential errors associated with each step. The study identified all distinct operations within each risk category for potential contribution to risk.

Table I: The top five potential risk categories and the number of associated potential operations associated with each risk.

The top five potential risk categories and number of associated potential operations that could cause them are shown in Table I. The study concluded that, in general, the more complex the particular workflow and the more risk factors involved, the more apparent were the benefits of PFSs compared with vials. For example, of the 43 distinct operations determined for Contamination, both MDVs and SDVs were subject to 38 of these risk opportunities while PFSs were subject to only 23 of them. Similar differences were seen across the rest of the top five risk categories.

One can also relate the findings of the study to Six Sigma principles. Six Sigma principles are used to help mistake-proof products and/or processes and rely on the following general approaches:

• Eliminating the possibility of error

• Replacing a risky process with one that is more reliable

• Facilitating or making the task easier to perform

• Detecting errors before carrying out further operations

• Mitigating or minimizing the effects of error.

In the user interface study, the number of distinct steps involved in delivering vaccine from the three packaging platforms—up to 50 for multi-dose vials, 45 for single-dose vials, and 28 for PFSs—suggests an advantage to the simpler PFS protocol. By reducing the number of steps, there is less opportunity for error.

For example, PFSs have a demonstrated advantage in contamination control because needle changes and drawing drugs from vials (and all the contamination potential those steps entail) do not occur with prefills. Similarly, replacing a highly variable step like syringe filling by a clinician with highly precise aseptic machine filling can help assure administration of the correct dose, as well as reduce the likelihood of contamination. Finally, opportunities for administering the wrong dose or expired vaccine are minimized by labels being applied on every PFS by the manufacturer. Preapplied labels thereby facilitate the task so it is easier, and provide a means of detection as the PFS reaches the end user and point of use with a label. Readily apparent labels also enable corrective protocols to be followed immediately in the event an incorrect drug or incorrect dosage is injected, thus mitigating further effects of the error.

Being prelabeled, unit-dose, and ready-to-administer, PFSs embody "safety-by-design" because of their inherent simplicity to use, elimination of several error-prone steps in vaccine preparation and administration, reduced opportunity for syringe reuse and cross-contamination, and assurance of the correct dose. Printed peel-off labels on vaccine prefills can facilitate recording of batch numbers and updating immunization records.

A MARKET IN TRANSITION

The clinical and workflow benefits of PFSs compared with vials rest on the inherent differences required to prepare a dose of a vaccine, or any injectable, packaged in a unit-dose, ready-to-administer format versus a non-ready-to-use format, whether single or multi-dose.

With their inherently simple design, prefilled syringes do not rely on consistently flawless and technique and aseptic practices to reduce injection-related risks—instead, they completely eliminate the need for several of the preparation steps that open the door to avoidable risks and consume additional clinician time. In a sense, they embody safety-by-design principles that are important when considering human factors and the user interface.

The growing recognition of the many advantages of PFSs have fueled a significant shift towards their use for all vaccine types, most significantly influenza, where the percent of flu vaccine packaged in PFSs has grown from approximately 21% during the 2006–2007 campaign to 48% in 2012–2013 (12). In Europe, nearly all of these same vaccines brought to market are packaged in PFSs (13).

Further adoption of vaccines packaged in PFSs is expected to continue, for both new and currently marketed vaccines, particularly as clinicians and vaccine enterprise stakeholders look more closely at the implication of packaging at the user interface and understand the benefits PFSs offer in terms of greater efficiency and advancing best care.

Brian Lynch is program lead, Health Science and Technology, Immunization, Brian_Lynch@bd.com, and Philip Song is a quality assurance staff engineer, Philip_Song@bd.com, both at BD Medical–Pharmaceutical Systems.

REFERENCES

1. F. Zhou, presention at the 45th National Immunization Conference (Washington, DC, March 2011).

2. US Dept. of Health and Human Services, 2010 National Vaccine Plan, www.hhs.gov/nvpo/vacc_plan/2010%20Plan/nationalvaccineplan.pdf, accessed Sept. 10, 2012.

3. Health Industry Distributors Association, 2010–2011 Influenza Vaccine Production and Distribution Market Brief (Sept. 2011).

4. C.C. Pereira and D. Bishai, Expert Reviews 9 (11), 1343–1349 (2010).

5. CDC, The Pink Book—Epidemiology and Prevention of Vaccine-Preventable Diseases, W. Atkinson, S. Wolfe, and J. Hamborsky, eds, (Public Health Foundation, 12th ed., Washington DC, 2011).

6. D. Bishai, presentation at the World Vaccine Congress, (Washington DC, Apr. 2010).

7. Advisory Committee on Immunization Practices, MMWR 55 (RR15), 1–48 (2006).

8. G. Pugliese et al., Am J Infect Control 38 (10), 789–98 (2010).

9. New York State Department of Health, "Nassau County and State Health Departments Alert 36 Patients to Infection Control Error by Long Island Doctor," Press Release, Albany, NY, Jan. 15, 2008.

10. Experts123, "Why is Human Factors Engineering Important for Medical Devices?" http://www.experts123.com/q/why-is-human-factors-engineering-important-for-medical-devices.html~, accessed Sept. 24, 2012.

11. Interface Analysis Associates, Vaccine Primary Drug Container: Single-Dose, Multi-Dose, Pre-Filled Syringe Risks Analysis Report. On file at BD (2011).

12. Company Reports, IMS Data, National Influenza Vaccine Summits, BD Market Intelligence (2006–2012).

13. BD Market Intelligence (2009).