How to Deal With the New Realities of the Nation's Flu Vaccine System
Public Health Feature -- November 2001
By Laurie Stoneham
Andrew Eisenberg, MD, a family practitioner in Madisonville, administered some 4,000 doses of flu vaccine in 1999. He estimated he'd need somewhat less last year, but figured it would be business as usual and that his order would arrive sometime in September 2000. Wrong.
Dr. Eisenberg had ordered 3,000 doses through a distributor who kept promising him prioritized delivery, but last year's shipment never arrived. And he -- like thousands of other physicians in Texas and around the nation - was stuck, powerless to do anything but wait in a system that can no longer promise on-time delivery of vaccines.
"It was extremely frustrating," said Dr. Eisenberg, chair of TMA's Committee on Infectious Diseases. "I had patients coming in whom I told specifically to come back in October for a flu shot. I had to tell them 'I don't have it.' My advice to them was to get it wherever they could -- at a pharmacy, a senior center, wherever. I told them, 'It won't hurt my feelings. You need to get it done.'" Dr. Eisenberg ordered 1,000 vaccines this spring. He hopes to have his complete order by the end of this month, but there are no guarantees.
To compensate for these anticipated delays and the complexities of the flu vaccine system, organized medicine has worked with the Centers for Disease Control and Prevention (CDC) and manufacturers to change how vaccines are administered. Massive education campaigns are under way to inform physicians and the public that people at highest risk should be vaccinated first and that many patients can benefit from receiving their flu shots later in the season.
What Happened Last Year
A number of factors created last year's delay. First, the identification of one of the three viruses to be used in the vaccine occurred later than usual. And that same strain took longer to grow, which affected the production timetable for all four manufacturers.
In addition, the U.S. Food and Drug Administration (FDA), which oversees the production of vaccines, cited two of the manufacturers for "deviations from good manufacturing practices." One of those manufacturers, Parkedale Pharmaceuticals, never was able to achieve FDA compliance and dropped permanently out of the vaccine-manufacturing business last September, leaving a gaping hole in the number of doses available nationally.
These problems created chaos and fury as some physicians were left scrambling to find the vaccine wherever they could to give to their high-risk patients, while large retail chains were conducting mass flu vaccination clinics. Along with the scarcity came skyrocketing prices, which many believed were unfair and unnecessary.
To compensate for the Parkedale loss, CDC contracted with Aventis Pasteur, the nation's largest influenza vaccine manufacturer, to produce 9 million additional doses. Those doses weren't delivered until mid-December, and because both patients and physicians mistakenly believed it was too late in the season to be vaccinated, nearly 7 million of the "emergency" vaccines were not used.
To avoid last year's problems, the American Medical Association and CDC organized two roundtable meetings, "Influenza Vaccine: Delays and Shortages and How to Address Them," held in late March and August of this year. More than 50 people attended, representing manufacturers, distributors, vaccination providers, trade organizations, state medical societies, specialty medical societies, and government. Dr. Eisenberg represented TMA at the meetings, which resulted in broad acceptance and dissemination of original and supplemental recommendations of CDC's Advisory Committee on Immunization Practices (ACIP).
Designing the Annual Flu Vaccine
Because flu strains continually mutate, new vaccines have to be produced each year. The process begins with worldwide surveillance efforts that involve the World Health Organization, state and territorial epidemiological reporting in this country, and the U.S. Influenza Sentinel Physicians Surveillance Network of 450 physicians who gather and report data on flu activity. Texas has 14 sentinel network sites.
"We're trying to predict what's going to happen next year," explained Ray Strikas, MD, medical epidemiologist with CDC's National Immunization Program. "There are three different viruses, and we're predicting which two of the three are likely to cause disease. That part we get right nine out of 10 times," he said . "We can predict which ones might show up in a broad way, but we can't predict severity," he added.
Producing a flu vaccine is a rigorous and extremely "time-sensitive" process, according to Phil Hosbach, executive director of public business and immunization policy with Aventis Pasteur. The strains to be used in the vaccine are usually identified by CDC in the first quarter of the year. Then, manufacturers must produce a new FDA-approved drug in the following six months.
The strains are grown and purified in the laboratory and later grown for production in fertilized chicken eggs. At the height of its production cycle, Aventis Pasteur uses more than 100,000 eggs a day to provide a living environment for the virus to grow and replicate. From there, the viruses are killed, purified, concentrated, and formulated to create the final vaccine.
It's a three- to four-month window from the time the eggs are first injected with the virus until the final vaccine is packaged. And then more testing is still required. Every lot produced has to be sent to the FDA for testing.
As of Sept. 10, CDC estimated that three manufacturers would produce 79.1 million doses this year. About 56 percent of the supply was to be delivered by the end of October, an additional 31 percent will ship in November, and the final 13 percent will arrive no later than mid-December.
But those figures have been very fluid. In August, it was thought that 60 percent of the total doses would be available by the end of October, down from estimates in July that 64.5 percent of a projected 77.1 million total doses would be shipped by Halloween.
"In most years, 90 percent of the vaccine gets out by the end of October. Last year, 35 percent got out by October. This year, 56 percent will be out by the end of October and all should be out by mid-December. While there is still going to be a delay, the situation is not as bad as a year ago," said Dr. Strikas.
This Year's Players
Aventis Pasteur will produce approximately 40 million doses. The company promised to deliver at least 10 million (25 percent) doses by the end of September, with the remainder to arrive before Thanksgiving. It is the only company that provided and delivered on a detailed distribution policy.
Wyeth Lederle Vaccines is estimating production of nearly 20 million doses. While the company has not finalized a distribution plan, Wyeth spokesperson Natalie de Vane says shipments would take place from October through December.
PowderJect Vaccines Inc., a firm based in the United Kingdom that acquired Medeva Vaccines last year, did not release any data relating to its vaccine production, distribution schedule, or pricing.
Vaccinating Later and Longer
To handle these delays, ACIP recommends a tiered approach to vaccinating highest-risk persons first in October and extending the conclusion of optimal vaccination time from mid-November to the end of November. ACIP also recommends that efforts to vaccinate individuals should continue through December and later, even if influenza is occurring in the community.
Physicians are reminded to ask patients if they received a pneumococcal vaccine. The shot needs to be administered only for people aged 65 or older.
During 19 influenza seasons from 1982 to 2000, influenza peaked in January or later in 15 seasons, and in February or later in 10. In Texas, the flu season typically shows up in January. Vaccines begin offering protection within two weeks, so administration in December or even January should have an impact in most influenza seasons.
The ACIP recommendations also suggest that organized vaccination campaigns be scheduled later in the season (mid-October and later) to minimize the need for cancellations because vaccine is unavailable. Sponsors of employee-based campaigns, which primarily immunize a healthy, younger population, have also been asked to postpone campaigns even later, particularly if there is a significant delay or shortage of vaccine, so that high-risk individuals may be immunized first.
To avoid the supply problems from last year, AMA and CDC urged physicians to order vaccines by early May. Some physicians and other vaccine providers double- or even triple-ordered from various suppliers to ensure getting the amount they need. The vaccine supply was booked by mid-May, according to CDC, although manufacturers and distributors were putting together waiting lists through the spring and into the summer. The overbooking made ordering more difficult for some physicians, particularly in solo or small practices.
Pricing and Reimbursement Increase
In keeping with the supply and demand principles, last year's delays resulted in price increases. The doubling and tripling of prices were considered by some as price gouging. And while the delays were a temporary situation last year, the price hikes are here to stay.
Last year, Aventis Pasteur's list prices ranged from $2.90 to $4.10 per dose. The vaccine is shipped in 10-dose vials, the minimum order the company will accept. This year, the Aventis Pasteur list price is $5, representing a 22- to 73-percent jump. Wyeth's catalog price this year is $5.29 per dose, up from $4.25 last year, a 24-percent increase. There is no word yet from PowderJect on its pricing.
Len Lavenda, spokesperson for Aventis Pasteur, says its price increases are due to three factors: expansion of its production facilities to make 20 percent more vaccine because of the Parkedale closure, continued investment to maintain compliance with FDA regulations, and increased expenses associated with making partial shipments throughout the season.
Medicare is reimbursing $7.12 per dose in Texas, along with an administrative payment. Medicaid reimburses for the expense of adult vaccines plus an administrative fee.
Distributing the Vaccine
According to CDC, the public health system -- state, federal, military, and Veterans Administration -- buys only 10 to 15 percent of the vaccine supply each year. The rest goes to private physicians, hospitals, long-term care facilities, and corporations. Most vaccinations occur in physicians' offices.
Physicians can buy the vaccine through a number of entities, including vaccine distributors, managed care organizations that buy huge quantities, state and federal contracts, and directly from the manufacturer.
But, buyer beware. Unlike in years past, unused vaccine can no longer be returned for a refund. According to Mr. Hosbach, beginning around 1993, along with an increase in vaccine production and supply came an increase in returns. Aventis Pasteur has seen return and refund rates of 10 to 15 percent annually. Because the vaccines can't be reused, they are destroyed.
The new no-return policy was implemented, according to Mr. Hosbach, "to address people double-ordering, then later canceling those orders, and to discourage some of the resulting vaccine wastage. There are some people who aren't really happy with the no-return policy, but we think it is the reasonable and right thing to do to ensure that everyone gets vaccine who needs it," he said.
Both Aventis Pasteur and Wyeth will be notifying customers of ship dates. Orders can be canceled without penalty before shipment. PowderJect would not comment on its policies.
Flu in Texas
The Texas Department of Health (TDH) has ordered 350,000 doses for local health departments, TDH regional offices, and federally qualified health centers. TDH has also used federal funds to purchase 70,000 doses for the Texas Vaccines for Children Program for children who are at high risk for flu complications. Up to 5 million doses of flu vaccine are expected to be administered by Texas physicians and other health care professionals this year.
Lisa Davis, TDH immunization coordinator, has heard from various organizations that a number of private physicians did not order vaccines this year because of ordering, supply, and pricing concerns. She's worried that fewer private vaccinators will put a strain on the public health system.
A survey conducted by AMA and CDC found that 7 percent of the physicians questioned had decided not to give flu shots because of ordering difficulties. Another 6 percent were getting out of the business because Medicare reimbursement was inadequate. While reimbursement does actually cover the cost this year, the increased reimbursement rate of $7.12 per dose was not announced until Sept. 1, when it was too late to place orders.
Healthy Endings (see page 76, November Texas Medicine ) offers your patients guidelines on who should be vaccinated and when. CDC and TDH also have a variety of patient education materials.
Dr. Eisenberg describes the real-world dilemma that he and his colleagues face because of the supply problem and the need to vaccinate the at-risk population first. "Someone comes to your office and asks for flu vaccine, and if you have it, he's going to want it. He's going to say, 'Oh, that person got one, and I didn't.' So you're kind of stuck. It is very difficult for practicing physicians to turn people away who want the vaccine, but that's really what would be recommended from a public health standpoint."
Not Ideal But Good Enough for Now
Dr. Strikas points out that while not perfect, the flu program in this country continues to expand, and to a degree is a victim of its own success. A decade ago, only 30 million doses of vaccine were manufactured and distributed. Today, that number has nearly tripled because of several factors. Medicare began reimbursing for the vaccine in 1993, and a variety of both public and private entities promoted the value of annual flu vaccinations.
Dr. Strikas says that last year's difficulties demonstrated the complexities of what he calls "a fairly fragile" system. "There are only the three companies, and we have to work with them to get what we want, realizing again that a huge amount more vaccine is getting out there than had for many years. It's unfortunate that it's not enough for all for whom it's recommended, but on the other hand, it's a lot more than we used to use, and therefore we're doing more good with it."
- Influenza is responsible for about 20,000 deaths per year in the United States.
- About 114,000 influenza-related hospitalizations occur per year, with 57 percent of all hospitalizations occurring among people over age 65.
- Infection rates are highest among children.
- Serious illness and death rates are highest among people over age 65 and people with chronic medical conditions.
- Influenza A (two types) and B are the two types of influenza viruses that cause disease epidemics.
- New influenza virus variants result from frequent antigenic change. The incubation period for influenza is one to four days, with an average of two days.
- Adults can be infectious starting the day before symptoms begin through approximately five days after illness onset; children can be infectious for a longer period.
- Influenza can exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease), lead to secondary bacterial pneumonia or primary influenza viral pneumonia, or occur as part of a co-infection with other viral or bacterial pathogens. Influenza infection has also been associated with encephalopathy, transverse myelitis, Reye's syndrome, myositis, myocarditis, and pericarditis.
- Among persons over age 65, influenza vaccination levels increased from 33 percent in 1989 to 63 percent in 1997 and 1998.
Source: CDC Advisory Committee on Immunization Practices
How We're Doing
The goal of the U.S. Department of Health and Human Services' Healthy People 2010 program is to vaccinate 90 percent of people aged 65 and older and 90 percent of the individuals living in nursing homes. The Centers for Disease Control and Prevention (CDC) estimates it would take between 109 million and 115 million doses to vaccinate everyone in at-risk categories.
In 1998, according to CDC National Immunization Program data, vaccinations were given to:
- 63 percent of individuals aged 65 and older,
- 83 percent of nursing home residents,
- 31 percent of individuals aged 18-64 with high-risk conditions,
- 43 percent of people aged 50-64 with chronic medical conditions,
- 29 percent of people aged 50-64 without chronic conditions,
- 23 percent of adults younger than age 50 with chronic conditions,
- 9 to 10 percent of asthmatic children, and
- 37 percent of health care workers.
According to a study sponsored by the Agency for Healthcare Research and Quality and published in the September 26, 2001, issue of the Journal of the American Medical Association , flu shots are less popular among African-Americans. Researchers found that 68 percent of whites received flu shots, while only 46 percent of African-Americans did. Those findings are based on 13,674 responses to the 1996 Medicare Current Beneficiary Survey.
For Additional Assistance
Texas Department of Health Immunization Division
Influenza Vaccine Questions
Latest Information From the Centers for Disease Control and Prevention
For Patient Reminder/Recall System
2001-02 Advisory Committee on Immunization Practices Recommendations
The ideal time to vaccinate high-risk populations is October and November. The Advisory Committee on Immunization Practices recommends that individuals receiving vaccines be prioritized as follows and that at-risk patients continue to be vaccinated even into December and beyond.
Individuals who are at increased risk for complications from influenza:
- People over age 65;
- Residents of nursing homes and other facilities that house people of any age with chronic medical conditions;
- People with chronic pulmonary or cardiovascular system disorders;
- Adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications or by HIV);
- Children and teenagers (6 months to 18 years) who are receiving long-term aspirin therapy and may be at risk for developing Reye's syndrome after flu infection; and
- Women in the second or third trimester of pregnancy during the flu season.
- Health care workers: Physicians, nurses, other personnel in hospital and outpatient-care settings, and emergency response workers.
Late October or November
Mass vaccination campaigns in the following locations outside workplaces should take place when vaccine supplies are assured: health departments, clinics, senior centers, and retail stores.
Special efforts should be made to vaccinate the elderly and those at high risk of influenza complications.
Beginning in November and Later
People in contact with those at highest risk:
- Employees of assisted living residences, nursing homes, and chronic-care facilities;
- People who provide home care to high-risk individuals;
- Household members, including children, living with high-risk individuals;
- Healthy people aged 50-64;
- Anyone else wanting to reduce their risk for influenza; and
- Work sites and campaigns that vaccinate healthy individuals.
People unsure of their risk factor should discuss it with their physician and be vaccinated when complete orders have been received.
December and the Remainder of the Flu Season
Continue vaccinating all patients, especially those at high risk and in other target groups.
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