Fingers Crossed

Edition: October 2005 - Vol 13 Number 10
Article#: 2241
Author: Repertoire

As late as Aug. 30, public health officials, doctors and distributors had been looking at a flu vaccine situation shaping up to be just as hair-raising as it was last year. At that time, they could absolutely, positively count on just one manufacturer, Swiftwater, Pa.-based sanofi pasteur (formerly Aventis Pasteur), to come through with a sizable amount of vaccine. But that changed on Aug. 31. That’s the day the Food and Drug Administration (FDA) approved GlaxoSmithKline’s Fluarix vaccine in time for the upcoming season. That same day, it gave high marks to Chiron Corp.’s continuing efforts to improve its flu vaccine manufacturing process, though it stopped short of giving the company final approval to sell its Fluvirin vaccine into the U.S. market.

As it did last year, Gaithersburg, Md.-based MedImmune was expected to provide its FluMist nasal spray vaccine through Henry Schein’s General Injectables and Vaccine subsidiary. At press time, the company would not reveal how many dosages it would make available, only that it expects “a modest sales increase” over last year, when the company provided just over 2 million doses. Regardless of the exact number, FluMist will probably be a drop in the bucket considering the 100 million doses of flu vaccine that the Centers for Disease Control and Prevention (CDC) says are needed to protect the U.S. population in the coming season.

Delivered intranasally by sprayer, FluMist contains live, weakened viruses, in an approach similar to vaccines for measles, mumps, rubella and chickenpox. The other flu vaccines are made from inactivated viruses, and are delivered intramuscularly by injection. FluMist has been approved for use among healthy persons aged 5 to 49, whereas inactivated influenza vaccine has been found suitable for all persons over age 6 months, including those with chronic medical conditions.

Indeed, the situation at press time was still dynamic. Emeryville, Calif.-based Chiron, whose Fluvirin was pulled from the U.S. market last year due to problems at the company’s manufacturing plant in Liverpool, England, appeared close to receiving a final verdict from the FDA following the agency’s July 2005 inspection of the same facility. “We are pleased that the Chiron Corp. has taken steps to address issues at their facility in Liverpool as they prepare for the upcoming flu season,” said Dr. Jesse Goodman, director of the FDA’s Center for Biologics Evaluation and Research in a statement dated Aug. 31. “The letter that we issued to them this week is a positive development and shows significant progress on their part.” However, Goodman said that additional work was needed to determine the amount of vaccine Chiron would be able to supply the U.S. market. He added that any vaccine produced must pass all tests for safety and potency before it could be sold.

For its part, Chiron was encouraged enough by the FDA’s actions to continue developing Fluvirin for the upcoming season. A company spokeswoman said the company hoped to provide between 18 million and 26 million doses to U.S. providers – about half of what it had promised to deliver last year before the FDA closed its facility.

Meanwhile, GlaxoSmithKline’s announcement was cause for celebration among public health officials. The Philadelphia-based company had filed a Biologics License Application for Fluarix with the FDA in May 2005. (Fluarix, which is available exclusively in pre-filled syringes, is already sold in 79 other countries.) The CDC estimates that approximately 8 million doses of Fluarix will be available in the United States for the 2005-2006 flu season.

It will be distributed through Temecula, Calif.-based FFF Enterprises and Richmond, Va.-based McKesson Medical-Surgical Inc. (After Chiron’s Fluvirin was pulled from the market last year, GlaxoSmithKline received FDA approval to sell approximately 4 million doses of Fluarix into the U.S. market on an emergency basis.)



Same old same old

Although certainly not by choice, industry veterans are getting used to the annual suspense associated with flu vaccine.

“For the last seven years, it’s been anything but predictable,” says Gene Alley, president, STAT Pharmaceuticals in Santee, Calif. “This, unfortunately, is another unpredictable year.”

STAT Pharmaceuticals distributes pharmaceuticals throughout the United States, and medical-surgical supplies primarily throughout southern California. At press time, the distributor was assured of having just one flu vaccine, sanofi pasteur’s Fluzone, for sale this season.

It hasn’t always been this way. Alley says the market ran pretty much like clockwork until the late-1990s. That’s when Parke Davis (now Pfizer) and Wyeth experienced problems with their flu vaccines and pulled out of the market. Chiron’s problems last year hearkened back to those earlier days. Following the shutdown of Chiron’s manufacturing facility in October 2004, the entire U.S. supply of vaccine was roughly halved, from about 100 million doses to about 50 million.

The effect on distributors was profound. For example, FFF Enterprises, which stands to be the biggest U.S. distributor of flu vaccine this flu season, lost $100 million in top-line revenue, according to President and CEO Patrick M. Schmidt.



Loss of confidence

“But aside from the numbers and the economic hit, the industry as a whole took a hit,” says Schmidt. Simply put, years of unpredictability have caused the market to lose confidence that it will have vaccine when needed. And that leads to all kinds of problems.

“In the flu vaccine delivery business, vaccine has to hit a willing patient simultaneously,” says Schmidt. If a vaccine clinic is announced but then cancelled for lack of vaccine, patients might not come back to get their shot, he says. “Any time we have a shortfall, demand is suppressed,” he says. Patients think, “I did OK last year; maybe I just won’t get one this year.” This line of reasoning leaves manufacturers in a quandary as to how much vaccine to produce (not to mention the potential health hazards).

Unsure of whether they will be able to get vaccine, nervous providers overbook, placing multiple orders with multiple distributors. (Distributors are not immune from this response either, according to experts.) Alley conjectures that if all the current orders from end-users for flu vaccine were tallied, they would exceed by three times the 80 million doses that can realistically be produced for the upcoming season.

Distributors react accordingly. “There’s a horse race in the flu vaccine business: who can get it to the customer first,” says Schmidt. Distributors don’t want to get stuck holding the bag in case their customers have booked vaccine from another company.

Sales reps’ role

In a nervous market, distributors are looking to the people on the front line, that is, their sales reps, to restore a sense of order and confidence among their customers.

“We tell our sales reps to work closely with their customers to find out exactly what their needs are, then to get [vaccine] to them on time,” says Schmidt.

In some cases, sales reps may be the bearers of bad news to overanxious customers. Yet they must persist in asking direct questions and providing straight answers, according to experts. That’s precisely what FFF Enterprises has instructed its reps to do. “Their message is, ‘Tell us when your clinic is vaccinating, so we can get vaccine to you on time,’” says Schmidt. “If it’s in October, don’t expect us to get it to you in August. Let’s try to meet the immediate demand.’”

Meanwhile, the CDC has promised to establish an improved “secure data network” should shortages occur. According to the CDC, the network would identify nationally and by state the following information:

• Providers that have pre-booked vaccine and the manufacturer/distributor with whom it has booked its order

• Location of these providers

• Amount of vaccine for priority groups

• Total amount ordered

• How much vaccine was actually shipped to providers and when.



Extending the flu vaccine

Regardless of a potential shortage, new technologies are coming to market that can extend the supply of flu vaccine. For example, the BD Integra Syringe has a low waste-space volume that will help extend vaccine supplies. The design minimizes the waste-space area to maximize the number of doses from each multi-dose vial. By using the Integra, physicians can vaccinate 11 patients on average with each multi-dose vial of influenza vaccine.



Future years

Chances are that market dynamics will be just as interesting a year from now as they are today. In the midst of rumors regarding new competitors entering the U.S. market, established manufacturers will have to make some tough decisions about whether to increase capacity or not. Distributors will need to do the same. Lots of dollars are riding on the answers. For example, STAT Pharmaceuticals increased its refrigeration capacity last year, anticipating increased product. And, earlier this year, FFF Enterprises spent $500,000 upgrading its refrigeration capacity.

Manufacturers remain confident. “As the years progress, we hope to continue to increase our capacity [of flu vaccine],” says GlaxoSmithKline spokeswoman Amanda Foley.

Meanwhile, in April 2005, sanofi pasteur received a $97 million contract from the U.S. Health and Human Services Department to speed the production process for new cell-culture influenza vaccines in the United States, and to design a U.S.-based, cell-culture vaccine manufacturing facility. Cell culture is an emerging technology, which eliminates the need for chicken eggs in the production of flu vaccine, according to the company.

In addition, the process has the potential to reduce from four weeks to two or three weeks the start-up time for manufacturing once the virus strain has been identified. Sanofi pasteur predicts that a cell-culture production plant could produce as many as 300 million monovalent influenza vaccine doses in case of a flu pandemic.



Helping Customers Control flu





An understanding of how the flu is transmitted, and the right mix of products, can prevent the virus from spreading among your customers.

An excellent source of information is the Centers for Disease Control and Prevention (CDC, www.cdc.gov). Meanwhile, the products that your customers should have in stock this flu season include tissues and masks, gloves and gowns, and hand-washing supplies and equipment, including soap and alcohol-based hand rubs.



How it spreads

Human influenza is transmitted from person to person primarily via virus-laden large droplets, which are generated when infected persons cough or sneeze, according to the CDC. These large droplets can then be directly deposited onto the mucosal surfaces of the upper respiratory tracts of susceptible persons who are near (that is, within 3 feet of) the droplet source. Transmission may also occur through direct and indirect contact with respiratory secretions. (Transmission from environmental surfaces has not been demonstrated by epidemiologic studies, according to the CDC.)

Immunization of healthcare personnel is the first line of defense. But healthcare workers should also implement the following: programs in respiratory hygiene and cough etiquette, Standard Precautions and Droplet Precautions, and restriction of ill visitors and personnel.



Respiratory hygiene and cough etiquette

The CDC states that respiratory hygiene and cough etiquette should be implemented at the first point of contact with a potentially infected person to prevent the transmission of all respiratory tract infections. Respiratory hygiene/cough etiquette programs include:

• Posting visual alerts instructing patients and persons who accompany them to inform healthcare personnel if they have symptoms of respiratory infection

• Providing tissues or masks to patients and visitors who are coughing or sneezing, so they can cover their noses and mouths

• Ensuring that supplies for hand washing are available where sinks are located and providing dispensers of alcohol-based hand rubs

• Encouraging coughing persons to sit at least 3 feet away from others, if possible.



Standard precautions

During the care of any patient with symptoms of a respiratory infection, healthcare personnel should adhere to standard precautions:

• Wear gloves if hand contact with respiratory secretions or potentially contaminated surfaces is anticipated

• Wear a gown if soiling of clothes with a patient’s respiratory secretions is anticipated

• Change gloves and gowns after each patient encounter, and perform hand hygiene

• Decontaminate hands before and after touching the patient, after touching the patient’s environment or after touching the patient’s respiratory secretions, whether or not gloves are worn

• When hands are visibly soiled or contaminated with respiratory secretions, wash with soap (either plain or anti-microbial) and water

• If hands are not visibly soiled, use an alcohol-based hand rub for routinely decontaminating hands in clinical situations; alternatively, wash hands with soap (either plain or anti-microbial) and water.



Droplet precautions

In addition to standard precautions, healthcare workers should adhere to Droplet Precautions during the care of a patient with suspected or confirmed influenza:

• For hospitals: Place patient in a private room or, if a private room is not available, place suspected influenza patients with other patients suspected of having flu; cohort confirmed flu patients with other patients confirmed to have flu

• Wear a surgical or procedure mask upon entering the patient’s room or when working within 3 feet of the patient; remove the mask when leaving the patient’s room and dispose of the mask in a waste container

• If patient movement or transport is necessary, have the patient wear a surgical or procedure mask, if possible.



Restrictions for healthcare personnel



Your customers need to keep their eyes on their own workers as well as patients and visitors, according to CDC. They should evaluate healthcare personnel with flu-like illness and perform rapid diagnostic tests to confirm that the causative agent is, indeed, flu. (Diagnosing flu on the basis of symptoms alone is tricky, because symptoms from illnesses caused by other pathogens can overlap considerably with flu.) Those in the healthcare setting must determine whether the personnel should be removed from duties that involve direct patient contact. (This is especially important for those who work in long-term care facilities and certain patient-care areas, such as intensive care units, nurseries or organ-transplant units). If excluded, such workers should refrain from providing patient care for five days after the onset of symptoms.



For more information, see the CDC’s “Guidelines and Recommendations: Updated Infection Control Measures for the Prevention and Control of Influenza in Health-Care Facilities,” published Jan. 20, 2005, at www.cdc.gov/flu/professionals/infectioncontrol/healthcarefacilities.