THE PANDEMIC VACCINE PUZZLE Part 2: Vaccine production capacity falls far short

first_img “We have been working at the federal, state, even the local level to try to make sure this issue is visible,” he said. “To date, the results have been underwhelming.” “Everyone understands that if you don’t have vaccine you are dead in the water, but what has not been dealt with is that, if you don’t have the syringes and needles, the vaccine doesn’t do you any good,” said George Goldman, senior director for hypodermics at BD Medical Surgical Systems in Franklin Lakes, N.J. “Six hundred million devices, which is what in theory would be required to vaccinate the US population twice, is a very large volume if you plan for it and an even larger volume if you produce them in a reactive mode. We do not believe the industry is capable of producing that kind of volume in any short period of time under the best of circumstances” (see Bibliography: BD 2007). Food and Drug Administration (FDA) planners have accepted that, absent rapid changes in current flu-vaccine manufacturing techniques, delivering the earliest doses of a vaccine tuned to a newly emerged pandemic strain would take a minimum of 4 months (see Bibliography: Goodman 2006). A vaccine-industry scenario, described in August in the journal BioPharm International, goes out 6 months: 3 to 4 months to generate a seed strain, 4 to 6 weeks of manufacturing set-up, and 18 weeks of production, including 2 to 3 weeks of quality assurance and regulatory approval—all adding up to a vaccine product that would arrive roughly in time for the pandemic’s second wave but long after the first patients had recovered or died (see Bibliography: Thomas 2007). The nine countries—France, Germany, Italy, The Netherlands, Switzerland, the United Kingdom, the United States, Canada, and Australia—trade vaccine across borders but are unlikely to keep doing so in a pandemic, he added: “In 2000, a total of six western European companies distributed 66 million doses of vaccine to 18 western European countries. Only 42% of these doses were distributed within the countries that produced them; the remaining 58% were exported to other western European countries. For the rest of the world, about 40% of the doses used in central and eastern Europe, 60% of the doses used in the western Pacific and Southeast Asia, and virtually 100% of the doses used in Latin America, the eastern Mediterranean, and Africa were imported from one or more of the nine vaccine-producing developed countries” (see Bibliography: Fedson 2003). While the US government has taken initial steps to support manufacturers—witness the $133 million given to two manufacturers this past summer to retrofit existing plants and the $1 billion awarded for cell-culture research—much more is needed (see Bibliography: HHS 2006, 2007). What about vials and syringes? While vaccine manufacturers are likely grateful for the HHS funding, others in the industry say the investment is incomplete—because it does nothing to expand capacity for critical downstream tasks such as bottling and administering completed vaccine. But the more difficult obstacle is not the time needed to produce vaccine—which newer technologies such as cell culture could shorten to some degree—but the amount of vaccine needed. Despite years of work, the grave mismatch between predicted demand and likely supply has yet to be solved. Little incentive to buildMany experts have warned that the only way to expand flu-vaccine manufacturing capacity is to get governments to pay for it. In its 2004 “Consultation on priority public health interventions before and during an influenza pandemic,” the WHO cautioned: “Industry has little incentive to build additional manufacturing capacity, which requires very large long-term investments for an event that occurs only rarely and unpredictably.” (See Bibliography: WHO 2004) Last year, Britain’s Royal Society added bluntly: “It is not commercially viable for the vaccine industry to commit the necessary resources to scale up production in advance of a pandemic when there is no existing market, the threat of a pandemic may be years away and the risk in any single year may be considered to be low” (see Bibliography: Royal Society 2006). The pandemic vaccine puzzle Manufacturing 600 million syringes would take 2 years if manufacturers used only their existing excess capacity, Goldman said, and creating a new manufacturing line takes approximately a year. A vaccine embargo?The WHO analysis hides a number of highly optimistic assumptions, including zero glitches in production and 100% cooperation by regulators. But the greatest assumption may be that the newly produced pandemic vaccine would be distributed equitably to all comers around the globe. It is more likely that vaccine would never leave the countries where it is produced. The WHO plan asks countries that do not now use seasonal flu vaccine to launch new seasonal vaccination campaigns as a way of stimulating demand. It also asks countries with existing vaccination programs to increase vaccine use, so that 75% of those for whom vaccination is recommended are taking the shot. Both recommendations may be unrealistic: The United States, which uses more vaccine than any other nation, has never reached 75% uptake even among groups that are urged to take the shot because they are at high risk for flu complications. In the 2005-06 flu season, according to CDC data published in September, the highest acceptance of seasonal flu shots—69.3%—was among adults older than 64, who are considered “high risk” because of their age. Fifty- to 64-year-olds who are at high risk because of chronic medical conditions had a vaccination rate of 48.4%; only 32.3% of those in the same age range who had no high-risk conditions took the flu shot, and only 18.3% of healthy adults between 18 and 50 did so (see Bibliography: CDC 2007). The “fill-finish” sector—which puts bulk manufactured vaccine into vials or syringes—is not being asked to prepare for any excess capacity, said Jack Lysfjord, vice-president for pharmaceutical consulting in the Valicare division of Robert Bosch Packaging Technology Inc., in Brooklyn Park, Minn., a leading manufacturer of production and fill-finish equipment. “We are talking to some companies, but we are not hearing that they plan to buy twice as much from us in the next five years,” he said. “If they want to expand, they should be starting production now” because building an automated filling line can take 2 years (see Bibliography: Bosch 2007). “I have never believed that boosting seasonal flu-vaccine demand was the way to prepare for pandemic flu,” said Michael Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy (CIDRAP), which publishes CIDRAP News, and of the National Institutes of Health (NIH)–funded Minnesota Center of Excellence for Influenza Research and Surveillance. “That economic model doesn’t work on its own and it has no scalability to provide flu vaccine for the rest of the world” (see Bibliography: Osterholm 2007). The companies that occupy the end of the vaccine-production process are also experiencing anxiety—on their own behalf and for the pharmaceutical manufacturers who feed product to them—that their operations will be disrupted by the start of a pandemic if they are brought into the process too late. In one example of the supply-demand mismatch, the United States plans to secure enough pandemic vaccine to deliver two doses to all 300 million of its residents (see Bibliography: FDA 2007: Committee meeting transcript). But current US manufacturing capacity tops out at 150 million 15-mcg doses, a total that is expected to rise to 250 million when a new Sanofi Pasteur plant comes online in 2008 (see Bibliography: Sanofi Pasteur 2007), but that still falls far short of the number the federal government hopes to deploy. And those hoped-for 600 million doses do not include the 40 million destined for the US pandemic stockpile that must be replaced periodically as flu strains mutate or the vaccine expires (see Bibliography: Riley 2007).center_img As a foreign-owned company, with its US unit in Minnesota and headquarters and manufacturing plants in Europe, Bosch feels this acutely. Much of the fill-finish equipment sold out of its US plant undergoes preliminary assembly in Germany, and many of the manufacturers for whom Bosch makes equipment rely on pharmaceutical ingredients or production components sourced from around the world. The same frustration is evident at BD (formerly Becton, Dickinson and Co.), the dominant company in syringe manufacturing. To be useful, those investments must be made well in advance of when vaccine is needed: The WHO estimates that building and licensing a new vaccine production line takes up to 5 years (see Bibliography: WHO 2004). The same scenario could happen again. “The U.S. will have a serious problem if the pandemic doesn’t strike in the next couple of years, because interest will decline and demand will go down again,” said Hedwig Kresse, an associate analyst for infectious diseases with the British-based market analysts Datamonitor. “Governments will have to guarantee a certain sales volume to keep [manufacturers] in the market and to keep these capacities up” (see Bibliography: Kresse 2007). Creating enough vaccine-manufacturing capacity to protect the world’s population is not cheap. The price tag is likely to be at least $2 billion and could rise to $9 billion, according to a WHO estimate (see Bibliography: WHO 2006: Global pandemic influenza action plan). Experts within the vaccine industry say that expecting manufacturers to make the investment asks companies to spend against their own best interest. “In the US market alone by the year 2010 there could be a surplus capacity resulting from ‘building for demand’ for pandemic preparedness but ‘suboptimal utilization’ based on significantly lesser demand for seasonal vaccines,” an engineer and two strategists from the Danish biotech firm NNE PharmaPlan wrote in the industry journal BioPharm International. “In Europe, Asia and the rest of the world, planned future capacities for ‘pandemic preparedness’ would have to address how potential surplus capacities can be effectively used in markets where there is little or no demand for seasonal vaccines” (see Bibliography: Thomas 2007). “If we really want to have surge capacity for pandemic vaccine, we have to invest in it like we do our oil reserves, or military reserve capacity,” Osterholm said. “The facilities may sit for years before they are utilized. But the analogy is having an airport fire department in case of a plane crash: You hope never to use it, but you invest as though it were a possibility” (see Bibliography: Osterholm 2007). Oct 26, 2007 (CIDRAP News) – The difficult reality is that, even if influenza science were perfect and research funding were abundant, achieving a widely deployable pandemic vaccine is currently out of reach. Chief among the reasons: The world lacks the manufacturing capacity to make enough vaccine to matter. “You have to think about every part of the components,” Lysfjord said. “The machines, the plants, the chemicals; the stopper, the glass, the aluminum overcast for the top of the vial; the labels. You’re not aware of how well-connected the system is until it breaks, and it is going to break big-time.” The United States has already experienced the aftermath of vaccine companies’ feeling overextended. Between 1998 and 2002, two of the four companies that then supplied seasonal flu vaccine left the market, citing losses on investment and increased regulatory demands. In the 2000-01 and 2003-04 flu seasons, the country experienced significant shortages of flu vaccine, with long lines, panic buying, price-gouging, and subsequent congressional investigations (see Bibliography: GAO 2001, 2004; Grady 2004). The World Health Organization’s (WHO’s) own best-case analysis, published in the agency’s 2006 “Global Pandemic Influenza Action Plan to Increase Vaccine Supply,” and updated in an Oct. 23, 2007, press release, breaks down the situation this way. In 2006, global manufacturing capacity for seasonal flu vaccine was 350 million doses per year of trivalent vaccine (comprising one 15-microgram [mcg] dose of each of three flu strains’ antigens). This year, according to the WHO, capacity could rise as high as 565 million doses, a total that incorporates both actual capacity increases achieved by manufacturers and theoretical capacity that would be created if manufacturing lines ran around the clock for the entire calendar year—something they do not do for seasonal flu-vaccine production. Given that a pandemic vaccine would be aimed at a single strain rather than three, global capacity could thus rise as high as 1.5 billion doses. But a pandemic vaccine would need to be given twice, because, unlike with seasonal flu, there would have been no prior exposure to the novel strain. So absent the use of adjuvants to stretch limited antigen supplies, industry could produce at best enough vaccine for 750 million people, far short of the amount needed to cover the world’s 6.7 billion inhabitants (see Bibliography: WHO 2006: Global influenza action plan; WHO 2007: Projected supply of pandemic influenza vaccine; Palkonyay 2007). The role of seasonal flu vaccine demandThe WHO action plan avers that manufacturers will significantly expand production capacity by 2012, largely because demand for seasonal flu vaccine will rise—but it offers no evidence that demand can be stimulated to levels that will persuade manufacturers to invest (see Bibliography: WHO 2006: Global pandemic influenza action plan). In the United States, for instance, the amount of vaccine manufactured has risen nearly every year, but so too has the amount returned to manufacturers unused. In the 2006-07 season, manufacturers selling to the US market delivered 120.9 million doses, the highest on record; they received back 18.4 million unused doses, also a record (see Bibliography: Santoli 2007). Editor’s note: This is the second in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 1 described how flu research has been a relatively low priority until very recently, which has left many important scientific questions unanswered. Seven hundred and fifty million “is fewer than the number of people that live in the nine countries that produce 85% of the world’s supply of flu vaccine,” said David Fedson, MD, a retired academic and vaccine-industry executive who has published critical analyses of pandemic-vaccine planning. “Which means that, if you live outside of a vaccine-producing country—whether that means Indonesia or Sweden or Spain—you get nothing” (see Bibliography: Fedson 2007: Author interview). Part 1: Flu research: a legacy of neglectPart 2: Vaccine production capacity falls far shortPart 3: H5N1 poses major immunologic challengesPart 4: The promise and problems of adjuvantsPart 5: What role for prepandemic vaccination?Part 6: Looking to novel vaccine technologiesPart 7: Time for a vaccine ‘Manhattan Project’?Bibliographylast_img read more

Kings buy out contract of defenseman Dion Phaneuf

first_imgThe Kings have bought out the final two years of defenseman Dion Phaneuf’s contract, the team announced Saturday. NHL free agency rumors: Sharks may be preparing to offer Erik Karlsson 8-year extension NHL trade news: Capitals send Matt Niskanen to Flyers for Radko Gudas BOUGHT OUT: The Los Angeles Kings have bought out veteran defenceman Dion Phaneuf.He had two years left on his seven-year, $49 million contract originally signed with the Toronto Maple Leafs in 2014. https://t.co/CTnr4z8dGo #TSNHockey pic.twitter.com/pBhWDMQcok— TSN Hockey (@TSNHockey) June 15, 2019The buyout will save the Kings $2.8 million and will open up $4 million of cap space next year, according to nbcsports.com.#LAKings have bought out the final 2 years of Dion Phaneuf’s contract.As a result of the Retained Salary trade between the Kings & Sens on Feb 14, 2018 involving Phaneuf, the cap hit resulting from his buyout will be split between LA (75%) and OTT (25%)https://t.co/u0YNYgG1Qy pic.twitter.com/golsF8VigN— CapFriendly (@CapFriendly) June 15, 2019Phaneuf was a first-round pick of the Flames (ninth overall) in the 2003 NHL Draft. He is a three-time All-Star and finished second in the voting for the Norris Trophy for the league’s top defenseman in 2007-08, his third season in the league. Related News At one time a premier defenseman in the NHL, Phaneuf, 34, appeared in 67 games for Los Angeles this past season and set personal lows in plus-minus (minus-21) and time on ice (15:00). He was acquired by the Kings from the Senators late in the 2017-18 season. He had four goals and 12 assists in 93 games with the Kings. He has 137 goals and 357 assists over his 14-year NHL career.last_img read more

Ibrahimovic to leave United?

first_imgZlatan Ibrahimovic left Manchester United after less than two years. One of the largest clubs in the world officially confirmed that Swedish striker will leave their team just three months before expiration of his contract.Ibrahimovic arrived at Old Trafford in the year of 2016 without compensation from PSG, and he was the best player of the United in the first season, which he did not finish due to a severe injury last April. After surgery and several months of recovery, he returned to football in December, but another injury prevented him to return to his former shape. Jose Mourinho recently announced Zlatan’s leave at the end of the season, but an offer from the US made everything faster.Ibrahimovic said goodbye to United and his fans on his Instagram in a quite shocking but effective way. In the photo, he is presented as Jesus playing hands with the red-devil, which is clearly United.“Great things also come to an end and it is time to move on after two fantastic seasons with Manchester United. Thank you to the club, the fans, the team, the coach, the staff and everybody who shared with me this part of my history,” wrote Ibrahimovic.Ibrahimovic started his career in Malmo back in 1999, and he played for Ajax, Juventus, Inter, Barcelona, AC Milan and Paris St Germain. He won a total of 31 trophies with six different clubs. He won the League Cup, the English Super Cup and the Europa League with the United last year.US media announced that his transfer to LA Galaxy will be officially confirmed very soon.(Source: N1)last_img read more

Sweet Spain memories for Chapa Dimba All-Stars

first_imgThe team of 32 with 17 boys and 15 girls were taken through a wholesome training program that covered the mental, physical and emotional side of the game at top level.For majority it was a dream come true after boarding the plane for the first time and to put icing ob the cake, they got a life time opportunity to tour the Camp Nou and watch a live match where Lionel Messi led his charges to a 2-0 victory over Getafe.The treat did not stop there as the team also toured the Espanyol Stadium, getting the opportunity to have a feeling of top professional successful clubs in Europe.Speaking to Capital Sport, Marion Iddi, a player from Al Alhy boys team in Kajiado, outlined that he is aspiring to return to Europe to play professional football and help national football team Harambee Stars succeed.“I have gained a lot, the coaches were good and also learnt from my team-mates too. The training has improved my skills, I now see myself a different person compared to when I came here,” Iddi, who looks up to Real Madrid goalkeeper Keylor Navas as his role model revealed.Chapa Dimba All-Stars keeper Marion Iddi during training in Spain.He added; “I have had good time; going to Camp Nou and Espanyol is a dream come true though the food is different from ours in Kenya. The pitches are out of this world compared to other stadiums, when I return to Kenya I want to be a role model to my fellow team-mates,” Iddi who also dreams of playing for Real Madrid narrated.His All-Stars team-mate Enock Wanyama had the same experience too, singling out the tour at Camp Nou as his best moments.“It has been amazing touring Camp Nou and watching a game live. Seeing Messi was unbelievable; I never thought I will be here but thanks to football here I am. Espanyol is also a good stadium and has good environment. We will be looking back and reflecting that we have made a mile stone as players from this trip,” Wanyama who plays for South B United narrated to Capital Sport.“Training has helped us to know that we need to work as a team, pass the ball and be patient to create chances. For me I have learnt that I need to hold the ball and make quick decisions,” he added.Enock Wanyama of Chapa Dimba All-Stars in training at Cambrillis, SpainWanyama , who is looking up to his name sake, Harambee Stars skipper and Tottenham Hotspur midfielder Victor Wanyama as his role model, is now focusing on inspiring his South B United from Nairobi region lift the Chapa Dimba Na Safaricom Nationals scheduled for June in Meru.“Back to Kenya, my concentration is winning the nationals because all the attention will be on me since I was in the All-Stars team so I want to prove that my selection was not by fluke by putting to actuality what we have learnt here in Spain.”Catherine Aringo of Chapa Dimba All Stars displays football skills during the Chapa Dimba Na Safaricom All-Stars trainings at Futbol Salou, Cambrils grounds in Spain.Her corresponding girls counterpart, King Lady Joy from Kwale Starlets is eyeing a selection in the national women’s football team, Harambee Starlets.“Experience gained here will help me thrive in football, I have improved in my skills, technique. Life is good in Spain but the only challenge is food. The weather is also good and environment appealing not like Kenya,” she expressed.“I want to return to Europe and play football here because its more professional, the pitches are marvellous.”-Coaches voice-The Chapa Dimba Na Safaricom All-Stars was coached by La Liga coachesWith only two Kenyan coaches managing to get the opportunity to travel to Spain, they were grateful to pick new ideas that will help them improve Kenyan football.“I have learnt a lot since training sessions are totally different compared to Kenya, as a coach I have gained a lot than the players and I will give the experience learnt back to the society especially now that we are heading to the nationals,” All-Stars ladies coach Pauline Awour said.“I am going to give my experience, tactical and skillful-wise to my fellow coaches in Kenya as well,” she added.”Her male counterpart Tedd Amusala revealed he is hoping to take his coaching to a higher level and his wish is to improve the state of Kenyan football in terms of positive results.The Chapa Dimba Na Safaricom All-Stars was coached by La Liga coaches“I There are some methods we have been using back at home that I think will come to an end because I want to put into practice what I have learnt in Spain like the game approach, team formation, keeping balance in defense and allowing the players to think and solve the situation,” Amusala who is aiming to win the national title with his boys team from Western stated.“I have also picked that the diet the players take does have an impact in their performance in the pitch. Back at home players are used to taking heavy meals, they need to avoid that especially before a game,” he added.“In life I want to prepare a team that will play one system that is building from the back, covering spaces, have balance in the defence and the creativity of the players; they should be able to think first on and off the ball.”The Chapa Dimba Na Safaricom All-Stars team was selected by scouts from La Liga as well as coaches from the eight regions in Nyanza, Western, Rift Valley, Eastern, North Eastern, Central, Coast and Nairobi.The team is scheduled to return home Thursday night from Spain to join their respective teams ahead of the nationals slated for June in Meru County.-Alex Isaboke is reporting from, Barcelona Spain –0Shares0000(Visited 3 times, 1 visits today) 0Shares0000Chapa Dimba Na Safaricom All-Star Team was selected from all the eight regions by La Liga scouts.SALOU, Spain, May 15 –The 10-day training camp in Salou, Spain has left sweet memories for the Chapa Dimba Na Safaricom All-Star teams, with the squad wishing it the dream come true could drag for a little while longer.The team has undergone a rigorous training period with top coaches seconded from La Liga and they jet back home Thursday night a much better side compared to when they set foot in Barcelona.last_img read more