My feature on Adimmune appeared today in the Taipei Times. I have reproduced the entire article here and added (different font) some of the material that was cut for length.The process through which Taichung County-based biotech company Adimmune Corp came to manufacture its A(H1N1) influenza vaccine was flawed and paved the way for safety concerns that have surrounded the vaccine, a US expert on infectious diseases told the Taipei Times this week. Ho Mei-shang (何美鄉), a research fellow at Academia Sinica’s Institute of Biomedical Sciences and former director of biotechnology research at Adimmune, disputes this view, however, saying in an interview on Tuesday that the vaccine is safe and that there was nothing wrong with the process.
The Centers for Disease Control (CDC) announced on July 13 that Adimmune, the sole bidder, had won a government contract to produce 5 million doses of the (A)H1N1 vaccine, at NT$199 per dose, for delivery by the end of October. By early this month, Adimmune had provided 6.95 million doses, while Switzerland-based Novartis had provided 2.02 million (at about NT$400 per dose), out of the government’s purchases of 10 million and 5 million doses respectively.
The government has spent NT$3 billion (US$94.4 million) purchasing vaccines from Adimmune.
The problems begin when looking at the chain of events that led to the awarding of the contract, the US expert said, speaking on condition of anonymity because of the sensitive nature of her position.
As early as May 5, the CDC said that Adimmune, in cooperation with the National Health Research Institutes, would manufacture a domestic influenza vaccine. This was more than a month before a WHO survey of global flu vaccine production capacity on July 7 concluded that countries such as Taiwan that had not placed early orders for the vaccine would not get any vaccine after November.
The Centers for Disease Control (CDC) announced on July 13 that Adimmune, the sole bidder, had won a government contract to produce 5 million doses of the (A)H1N1 vaccine, at NT$199 per dose, for delivery by the end of October. By early this month, Adimmune had provided 6.95 million doses, while Switzerland-based Novartis had provided 2.02 million (at about NT$400 per dose), out of the government’s purchases of 10 million and 5 million doses respectively.
The government has spent NT$3 billion (US$94.4 million) purchasing vaccines from Adimmune.
The problems begin when looking at the chain of events that led to the awarding of the contract, the US expert said, speaking on condition of anonymity because of the sensitive nature of her position.
As early as May 5, the CDC said that Adimmune, in cooperation with the National Health Research Institutes, would manufacture a domestic influenza vaccine. This was more than a month before a WHO survey of global flu vaccine production capacity on July 7 concluded that countries such as Taiwan that had not placed early orders for the vaccine would not get any vaccine after November.
This suggests that even before global capacity was known, the Department of Health (DOH) was already considering domestic production, which in essence means “siding with Adimmune,” the source said.
Adimmune’s chairman is Steve Chan (詹啟賢), deputy secretary-general of the Chinese Nationalist Party (KMT). Chan was also the deputy executive director of President Ma Ying-jeou’s (馬英九) presidential campaign.
For decades a producer of animal vaccines, Adimmune is the only firm in Taiwan with the capacity to produce human vaccines.
Prior to the A(H1N1) contract, it had never produced human vaccines on its own. All it did, the source said, was “package” vaccines made by other, mostly Japanese, companies.
Adimmune’s chairman is Steve Chan (詹啟賢), deputy secretary-general of the Chinese Nationalist Party (KMT). Chan was also the deputy executive director of President Ma Ying-jeou’s (馬英九) presidential campaign.
For decades a producer of animal vaccines, Adimmune is the only firm in Taiwan with the capacity to produce human vaccines.
Prior to the A(H1N1) contract, it had never produced human vaccines on its own. All it did, the source said, was “package” vaccines made by other, mostly Japanese, companies.
Ho admits that by July, the company had yet to complete the implementation of the automated software necessary for vaccine production.
Ho maintained, however, that through close cooperation with Japanese and Dutch vaccine makers, Adimmune “leapfrogged” and obtained the know-how to make human vaccines.
Most vaccine manufacturers, including GSK and Novartis, have decades of experience producing seasonal flu vaccines. While H1N1 is only a variant of the seasonal flu, major manufacturers usually obtain licensure from the US Food and Drug Administration (FDA) to expedite the process based on regulations regarding “strain change.”
Regardless, manufacturers providing H1N1 vaccines to the US have undergone clinical trials, most of which are sponsored by the National Institutes of Health (NIH).
EXPEDITED PROCESS
Adimmune, which had no experience producing the vaccine, should never have been allowed to enter an “expedited process,” the source said.
Adimmune only conducted a small-scale clinical trial with less than 500 subjects, far less than the 5,000 to 6,000 that are usually required for new vaccines.
Ho said that as the vaccine is based on the seasonal flu vaccine, it is not a new vaccine and therefore there was “no point” in conducting more rigorous testing.
The source, however, said that as Adimmune had never produced the seasonal flu vaccine, the Department of Health (DOH) should have demanded the company conduct more clinical trials.
“This is the scientific foundation to claim that a vaccine is ‘safe,’” the source said. “You can’t cut corners on this. Science requires replicability.”
In response, Ho said that, “lack of experience does not jeopardize quality. It just means more costs.”
Adimmune’s chairman has said that clinical trials are a “redundant procedure for bureaucrats,” adding that most Western countries had shortened them to speed up vaccinations.
In other words, despite its lack of experience, the company felt confident it could produce a safe product with few trials, while more experienced manufacturers that also entered an “expedited process” proceeded more cautiously — GSK did 6,340 tests, Novartis did 4,768 and the NIH conducted 3,951, data shows.
Ho maintained, however, that through close cooperation with Japanese and Dutch vaccine makers, Adimmune “leapfrogged” and obtained the know-how to make human vaccines.
Most vaccine manufacturers, including GSK and Novartis, have decades of experience producing seasonal flu vaccines. While H1N1 is only a variant of the seasonal flu, major manufacturers usually obtain licensure from the US Food and Drug Administration (FDA) to expedite the process based on regulations regarding “strain change.”
Regardless, manufacturers providing H1N1 vaccines to the US have undergone clinical trials, most of which are sponsored by the National Institutes of Health (NIH).
EXPEDITED PROCESS
Adimmune, which had no experience producing the vaccine, should never have been allowed to enter an “expedited process,” the source said.
Adimmune only conducted a small-scale clinical trial with less than 500 subjects, far less than the 5,000 to 6,000 that are usually required for new vaccines.
Ho said that as the vaccine is based on the seasonal flu vaccine, it is not a new vaccine and therefore there was “no point” in conducting more rigorous testing.
The source, however, said that as Adimmune had never produced the seasonal flu vaccine, the Department of Health (DOH) should have demanded the company conduct more clinical trials.
“This is the scientific foundation to claim that a vaccine is ‘safe,’” the source said. “You can’t cut corners on this. Science requires replicability.”
In response, Ho said that, “lack of experience does not jeopardize quality. It just means more costs.”
Adimmune’s chairman has said that clinical trials are a “redundant procedure for bureaucrats,” adding that most Western countries had shortened them to speed up vaccinations.
In other words, despite its lack of experience, the company felt confident it could produce a safe product with few trials, while more experienced manufacturers that also entered an “expedited process” proceeded more cautiously — GSK did 6,340 tests, Novartis did 4,768 and the NIH conducted 3,951, data shows.
Eric Althoff, head of global media relations at Novartis International AG, told the Taipei Times on Monday that the company “conducted an extensive clinical program for our H1N1 vaccines with more than 8,500 subjects.”
(The Novartis version of the vaccine sold to Taiwan is a H5N1 markup with an adjuvant, which was purchased via a special procurement as the adjuvant has yet to be approved in Taiwan.)
(The Novartis version of the vaccine sold to Taiwan is a H5N1 markup with an adjuvant, which was purchased via a special procurement as the adjuvant has yet to be approved in Taiwan.)
“Adimmune’s expertise is like that of an intern,” the source said. “Novartis, Sanofi and GSK’s experience makes them more like seasoned attending physician. When you need surgery, would you prefer an intern or an attending?”
Ho said that prior to delivery of the vaccine toward the end of October, the DOH’s Food and Drug administration conducted two weeks of tests. The FDA only became officially operational on Jan. 1 this year.
WHO guidelines for vaccine manufacturing show that three demo batches of a vaccine, as well as pre-approval inspection, must be completed before a vaccine can be released.
The source said Adimmune finished the clinical study on Oct. 21 and obtained the licensure on Nov. 12. The nationwide vaccine program started on Nov. 15.
“According to the timeline, Adimmune couldn’t have made it in three weeks,” the source said. “This means they mass produced before an approval [license] was granted,” the source said.
Ho confirmed this was the case.
“Adimmune was taking a chance,” Ho said, because if it failed to obtain approval, it would have “to discard all batches that had been produced beforehand.”
“I was among the very few top management team and I was adamant about going ahead to produce the vaccine as at that time, there appeared to [be] no other opportunity to secure H1N1 vaccines for ... Taiwan,” Ho said.
“My intention at the time was that we, the Taiwanese people ... would lose more if there was no H1N1 vaccine at all. Thus, with a certain degree of confidence in what Adimmune could achieve, the risk of failure was deemed slim and we went ahead,” Ho said.
“There was no ethical issue. It was all about regulation and it was OK as long as approval was obtained eventually,” she said.
“Because the approval was based on the inspection and documentation of consistency of three consecutive [vaccine] batches — even though the paperwork was completed later — it was retroactively applicable,” she said.
On Jan. 7, the DOH said autopsies showed that six of 17 deaths possibly related to the vaccine were due to other causes, with investigations continuing on the other 11.
Ho confirmed that all cases involved individuals who had received the Adimmune vaccine, adding that this didn’t mean the vaccine was less safe than Novartis’, as the majority of vaccines administered here were Adimmune’s.
The source also saw problems with the DOH.
ETHICS
“Again and again, DOH officials have sided with Adimmune, something I have never seen in the US,” the source said. “If the commissioner of the [US] FDA, the head of the [US] CDC or the NIH endorsed a certain brand, they not only would be in clear violation of ethics codes, they would be committing political suicide.”
When a legislator asked to monitor the egg production process (influenza vaccines are produced in fertilized chicken eggs), Adimmune said “it’s a commercial secret,” the source said. “Later, when the CDC head [Steve Kuo, 郭旭崧] was asked how the sterility of the eggs was assured, his answer was: ‘Adimmune examined it.’”
“Was there no DOH oversight?” the source asked.
Ho maintains that from the very beginning, the DOH kept a professional distance from Adimmune. There was no dialogue between Adimmune and the CDC, which was responsible for buying the vaccine, she said.
Despite Adimmune’s requests, the DOH also hasn’t allowed it to release clinical test results.
The reason, Ho said, is that “technically speaking, the clinical trial has not been finished.”
The contract stipulates that until then, no information can be disclosed.
WHO guidelines for vaccine manufacturing show that three demo batches of a vaccine, as well as pre-approval inspection, must be completed before a vaccine can be released.
The source said Adimmune finished the clinical study on Oct. 21 and obtained the licensure on Nov. 12. The nationwide vaccine program started on Nov. 15.
“According to the timeline, Adimmune couldn’t have made it in three weeks,” the source said. “This means they mass produced before an approval [license] was granted,” the source said.
Ho confirmed this was the case.
“Adimmune was taking a chance,” Ho said, because if it failed to obtain approval, it would have “to discard all batches that had been produced beforehand.”
“I was among the very few top management team and I was adamant about going ahead to produce the vaccine as at that time, there appeared to [be] no other opportunity to secure H1N1 vaccines for ... Taiwan,” Ho said.
“My intention at the time was that we, the Taiwanese people ... would lose more if there was no H1N1 vaccine at all. Thus, with a certain degree of confidence in what Adimmune could achieve, the risk of failure was deemed slim and we went ahead,” Ho said.
“There was no ethical issue. It was all about regulation and it was OK as long as approval was obtained eventually,” she said.
“Because the approval was based on the inspection and documentation of consistency of three consecutive [vaccine] batches — even though the paperwork was completed later — it was retroactively applicable,” she said.
On Jan. 7, the DOH said autopsies showed that six of 17 deaths possibly related to the vaccine were due to other causes, with investigations continuing on the other 11.
Ho confirmed that all cases involved individuals who had received the Adimmune vaccine, adding that this didn’t mean the vaccine was less safe than Novartis’, as the majority of vaccines administered here were Adimmune’s.
The source also saw problems with the DOH.
ETHICS
“Again and again, DOH officials have sided with Adimmune, something I have never seen in the US,” the source said. “If the commissioner of the [US] FDA, the head of the [US] CDC or the NIH endorsed a certain brand, they not only would be in clear violation of ethics codes, they would be committing political suicide.”
When a legislator asked to monitor the egg production process (influenza vaccines are produced in fertilized chicken eggs), Adimmune said “it’s a commercial secret,” the source said. “Later, when the CDC head [Steve Kuo, 郭旭崧] was asked how the sterility of the eggs was assured, his answer was: ‘Adimmune examined it.’”
“Was there no DOH oversight?” the source asked.
Ho maintains that from the very beginning, the DOH kept a professional distance from Adimmune. There was no dialogue between Adimmune and the CDC, which was responsible for buying the vaccine, she said.
Despite Adimmune’s requests, the DOH also hasn’t allowed it to release clinical test results.
The reason, Ho said, is that “technically speaking, the clinical trial has not been finished.”
The contract stipulates that until then, no information can be disclosed.
The fine for disclosing the information to the media? NT$200,000. Though Chan has allegedly said his company should disclose the information and absorb the fine, it has yet to do so.
“The DOH adamantly opposes disclosure,” Ho said. “That makes me think something is fishy.”
For the source, the vaccine mess is another example of the gambling attitude of the Ma administration, conflict of interest and lack of transparency.
“As a federal government employee with experience in issuing contracts, and as a medical professional, I would say that if the same process occurred in the US, not only would it [make] the headlines in the Washington Post, but criminal investigations would follow,” she said.
For Ho, the problem was poor government communication and media speculation. Chan’s role as chairman also made it easier to politicize the matter, she said.
“Adimmune is more than a private company — it does public health,” she said. “The firm could have gone bankrupt, but everybody worked hard to make it happen in time and provide Taiwan with a vaccine production facility.”
Asked if she’d taken the vaccine, Ho said, “Yes, — Adimmune’s.”
“The DOH adamantly opposes disclosure,” Ho said. “That makes me think something is fishy.”
For the source, the vaccine mess is another example of the gambling attitude of the Ma administration, conflict of interest and lack of transparency.
“As a federal government employee with experience in issuing contracts, and as a medical professional, I would say that if the same process occurred in the US, not only would it [make] the headlines in the Washington Post, but criminal investigations would follow,” she said.
For Ho, the problem was poor government communication and media speculation. Chan’s role as chairman also made it easier to politicize the matter, she said.
“Adimmune is more than a private company — it does public health,” she said. “The firm could have gone bankrupt, but everybody worked hard to make it happen in time and provide Taiwan with a vaccine production facility.”
Asked if she’d taken the vaccine, Ho said, “Yes, — Adimmune’s.”
My assessment is that Ho truly believes the Adimmune vaccine is safe. Adimmune Corp, and by extension the DOH all the way up to the Cabinet, saw in the A(H1N1) pandemic a chance to get production started. Real work had begun amid an earlier scare — H5N1 — and this is when Ho was invited to take leave from Academia Sinica to help out at Adimmune. Whether the company was ready to meet that challenge, or whether it cut corners, as the source alleges, to meet this on time, remains to be determined. The DOH’s handling of the controversy, meanwhile, raises age-old issues about the failure of the Chinese Nationalist Party (KMT) to separate the party from the state, and the state from the private sector. Where there should be a clear line between government bodies and private firms, what the Adimmune case presents us with is a firm that is chaired by a senior KMT official, with pressure within the DOH to side with Adimmune, something that, as the source points out, would be inconceivable in other countries. Failure to ensure the independence of all parties involved is the source of the controversy.
Chinese version follows:
Chinese version follows:
國光疫苗救命還是害命？
1 月16日的台北時報有一篇由Michael Cole 執筆，針對國光疫苗的報導，報導題為：國光疫苗救命還是害命？(
該報導分別訪問前國光研發執行長長何美鄉及一名美國傳染病專家。
一位美國專家表示國光生技進入H1N1疫苗生產的過程有瑕疵，
2009年6 月13日台灣疾管局宣布疫苗招標由唯一參與競標的國光得標，
問題出在國光得標的過程：
在競標之前，2009年5月5日，
國光董事長不僅是國民黨副秘書長，也是馬英九競選總部的副指揮。
過去國光只有分裝進口的流感疫苗，沒有自己生產。
目前大部分的疫苗廠都有數十年的生產經驗，雖然H1N1只是流感
快速審查
國光既然未曾生產流感，並不符合快速審查的規定；
何美鄉強調，H1N1不是新疫苗，「完全沒有必要」
美國專家指出，衛生署應該督導堅持該做的人體試驗，
然而何美鄉還是表示：沒有經驗不代表品質不良。
換言之，儘管沒經驗，做的試驗規模小，國光還是很有信心，
根據WHO的規定，疫苗上市前需做三個批次(batch)測試，
國光10月15日完成初步臨床試驗，11月12日拿到衛生署許可
何美鄉證實事實如此，表示國光冒了極大風險，
何承認目前17例死亡病例都是注射國光，
然而美國專家認為衛生署有極大問題。
工作倫理
「自始至終，台灣的衛生署一直幫國光講話，假如美國FDA、NI
當立委質詢胚胎蛋的無菌問題時，疾管局局長的回答是「
衛生署到底有沒有監督？
何美鄉表示，衛生署從一開始就與國光保持距離，並基於合約，
在美國專家的眼中，整個國光疫苗事件就是馬英九政府的賭博心態，
在國光研發執行長何美鄉眼中，問題出在政府溝通不良及媒體煽動，
何美鄉對國光有完全的信心，表示自己也注射了國光H1N1疫苗
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