Lantigen

Vaccine
Management Loophole

Scandal

Exposed

http://magazine.caijing.com.cn/20150427/3870423.shtml

An Italian imported drug has been existed in Chinas vaccine system for 8
years, and numerous children were vaccinated. This scandal in medical
vaccine field has directly exposed the management loophole in Chinas public
health system.
By correspondent: Gao Shengke (intern), Xie Ruyin
In April 2015, Citizen Li Fei (alias) of Shenyang, Liaoning province
discovered that the so-called category II vaccine Lantigen her son vaccinated
3 years ago was actually a kind of imported drug. On April 10 th,Yu Jingjin,
General Director of Disease Prevention and Control Bureau of National Health
and Family Planning Commission of PRC (NHFPC), made clear that Lantigen is
not a vaccine, but an approved biological product for treatment. It cannot be
used for vaccination in a report in 2015 of the State Disease Prevention and
Control Bureau of China.
Li Fei knew that she was cheated after reading the news. In August 2012,
the Disease Prevention and Health Protection Department of a hospital in
Dadong district, Shenyang, promoted Lantigen as a category II vaccine to
local parents. In most cases, Lantigen were highly recommended to parents in
the vaccination brochure. In Shenyang, children are advised to receive
vaccinations at one and 2.5 years old. However, Children in Beijing are
suggested to get vaccinations when they are 3-month, 9-month and 1.5 years
old.
Lantigen, also named Bacteria Solute in Chinese, is a product of
Bruschettini S.R.L from Italy. On April 21 st, the AIFA (Drug Administration of
Italy) stated that Lantigen is an oral medicine and can be used to prevent
respiratory infections, in its emailed response to the questions raised by a
reporter from Caijing, a China financial magazine.
Lantigen was originally approved to Chinese market in 2000, and in 2007,
it was included in the vaccine management system of China CDC (Center for
Disease Control). After which, most local CDCs and vaccination organizations
adopted Lantigen as a category two vaccination throughout the country. Since
then, this imported Italian drug has been placed in Chinas vaccination system
for 8 years, and was recommended as a vaccine to children.
The so-called category II vaccine is a kind of vaccine that citizen can get
on a voluntary basis at their own expenses. The contraindications on its
instruction brochure say do not use Lantigen if it is allergic to its ingredients.
However, many parents argued that the health care doctors failed to notify
them on this and emphasized that Lantigen could be used on healthy children
as well as those who had a cold.
All drugs has its contraindications and precautions, but these will be
ignored once the drug is included as vaccine, which posted a potential hazard
to public health, said Qiu Lufeng, professor in the law school of Nanjing
University with experience in medical management.

In March, several children were diagnosed with Kawasaki disease after

taking Lantigen in Jiangsu, Hebei, and other provinces in China. Concerns

were widely spread among parents. Kawasaki disease is a kind of vasculitic
syndrome, which can lead to serious cardiovascular diseases. However, the
causes of Kawasaki disease are complicated and cannot simply associate with
Lantigen.

Besides going against medical virtue, interviewed experts raised

awareness of side effects or adverse reactions to healthy children. Qiu Lufeng
appealed that it is necessary for the National Health and Family Planning
Committee (NHFPC) to launch an investigation on children who have used
Lantigen.
Vaccines and drugs are in two parallel but totally different circulation
systems; nevertheless, but they entangled now because of Lantigen, which
directly exposed the loophole in Chinas public health management system.
However, who should take the blame and how to fix up the existing loophole
are the leftover problems behind the Lantigen Scandal.
Escape from prescription regulation
On Bruschettinis Chinese official website, Lantigen was descripted by
using its exclusive patented technology and strictly following the European
GMP, and it was listed as other category of vaccine. In 1985, this product
was allowed in Italy. Lantigen is only sold in Italy up till now, AIFA said via
email.
On April 17, European Medicines Agency talked with Caijing via E-mail:
We are sorry that we cannot provide you the query information of Lantigen,
because it is not an certified drug by the authority, but please pay attention
that Lantigen is now under a central authorized scientific evaluation
procedure conducted by European Medicines Agency.
A person from Chinas CDC (Center of Disease Control) system who has
specifically studied on Lantigen said it was short of sufficient clinical data for
lantigen, not registered in European Medicines Agency, and not approved by
FDA. Besides, Lantigen is not included in Vaccinology, the worlds most
authoritativebook in vaccine.

AFIA noticed that Italy has a very strict requirement for the prescription of
Lantigen, and people can only purchase it with prescription one dose a time.
In addition, people should follow the doctors instructions when using it. All
these means indications and usages of Lantigen should be highly regulated.
Zhang Silai, a famous pediatric expert in China, says that Lantigen is an
oral prescription medicine under doctors instructions.

However, there is no prescription requirement for vaccine in Chinas

disease control system, so it is not necessary to get prescription before
recommending Lantigen to parents. In some cases, health care staffs are
nurses who dont have prescription rights. Those just need to attend and
obtain the vaccination working license in the trainings periodically organized
by CDCs of district and county level above.
After Lantigen was questioned, Bruschettini posted several articles on its
Chinese official website, emphasizing Lantigen could be used both for
prevention and treatment, and also adopted the noun of therapeutic

vaccine. In March 2015, two articles, which shared highly identical contents
describing Lantigen as a therapeutic vaccine, were posted on Health News
and China Pharmaceutical News. The two journals are under the
administration of NHFPC and China Food and Drug Administration (CFDA)
respectively.
The passage on China Pharmaceutical News says Lantigen is a kind of
man-made bacterial antigen extract, and it belongs to the therapeutic
vaccines.
In China, vaccines are used for prevention while drugs are for treatment.
Lantigen is registered as a category VII biological product, so it can be sold
namely outside of China, not domestically.
The so-called therapeutic vaccine is still at its conceptual level. In China,
Lantigen is still at research stage, so there is no a real therapeutic vaccine in
the market currently, said Zhao Kai, a member of the Chinese Academy of
Engineering and head of National Vaccine and Serum Institute.

Can drugs in clinical trial replace vaccines?

The imported drugs must be registered and get approval from Chinese
government, and the drugs must undergo 3 phases of clinical trials.
The reporters of Caijing Magazine found out that the Trendful
Development Limit SD from Hong Kong has helped Lantigen to get registered
and complete the required 3 phases of clinical trial. Moreover, the company
has become the first general agent of Lantigen in China. The company was
established in 1994 with its main business of helping imported drugs to get
registered and develop markets, as well as the promotion of imported drugs
from Italy.
When introducing Lantigen, we didnt not look into its registrations and
market status; what we mainly consider were the indications and whether it is
promising in profiting. A Trendful personal said. Lantigen is extracted from 6
processed bacteria and its indications are upper respiratory infections, like
rhinitis, amygdalitis, bronchitis, etc. The company believed Lantigen has a
potential market after introduction. And Bruschettini also thinks Lantigen is
more applicable in developing countries, like China.

The person from Trendful also disclosed that CFDA has selected the
designated hospitals in Beijing, Shanghai, and Guangzhou as the clinical trial
bases for Lantigen. The clinical trials were carried out under imported drugs
category, which took adults as the experimental subjects rather than children.
The clinical trial of vaccine and drug is essentially different
First, vaccine clinical trial is a prevention trial that targets at healthy
people, while drug clinical trials are therapeutic trials that target at patients
suffering from a specified illness. Second, the vaccine clinical trial has
different requirements for subjects at different phases. The safety test in the
first phase only needs dozens of people, and hundreds of people in the second
phase, however, in the third phase, several thousands of people or more are
needed.
The two papers, A Clinical Study on Lantigens Influence on Serum and

Saliva SIgA Level of patients who Suffer Repeated Respiratory Affection and A
Random Double-blinded Comparison Study on Polyvalent Bacteria Vaccine
Given Sublingually to Children who Suffer Repeated Respiratory Affection,
which were published in 2001 and 2004 respectively, pointed out that
Lantigen can help regulate the functions of human immune system and
protect people from respiratory affections. The authors of those two are from
respiratory departments of Peking University Peoples Hospital, China-Japan
Friendship Hospital, Zhongshan Hospital of Fudan University, and The First
Affiliated Hospital of Guangzhou University, etc. Several field experts
demurred on the scientificity of the three clinical trials of Lantigen. From
above mentioned papers, it was known that the patients rather than the
healthy people were chosen as the experiment subjects, which against the
vaccine trial theory. Moreover, the ESS (Effective Sample Size) of Lantigen was
120 and 86 people, which is not enough.
When Zheng Xiaoyu, the former head of CFDA, was in power, Lantigen got
its 3 clinical trials and the approval finally.

During his time, lots of new medicines were approved. Some drug
companies only paid tens of thousands Yuan to buy all the required materials
when registering, and used fake samples to pass all the tests of Institution for
Drug Control, which made obtaining approval of new medicine Chinese
featured.

After Zheng Xiaoyu was taken down, it was very difficult, even impossible,
to re-investigate all the approval files he left behind.
Bruschettini told Caijing Magazine that all the Lantigen in China are 100%
produced by them, and imported in its original packaging. All the products
registrations and sales channels are in accordance with related Chinese
regulations and standards, and Bruschettini reserves the right to the final
interpretation.

Rashomon of Vaccine information system

After Lantigen was approved in China, Trendful became its sole agency in
China. Trendful promoted Lantigen through hospitals, and the retail price was
188 Yuan per dose. However, the sole agency has shifted to another holder in
a few years later.
At that time, the agency contract was not expired, but the Italian
manufacturer demanded to end the it and hand its sole agency to others.
The Trendful said, The Italians insisted that we are failed in the marketing
campaigns, and not satisfactory with current sales volumes.
On the other hand, Bruschettini re-stated that their company has made
strict business cooperation strategies, and it is possible to adjust the
cooperation models according to the regular assessments of the market
changes, brand sales status, etc.
The new sole agency in China is Yu Shu Feng Pharmaceutical Co., Ltd in
Chongqing, which was established in August 2007 by Yang Jie, former general
manager of Mainland Pharmaceutical Co., Ltd in Shanghai.
Wu Jianwen, former president of Shanghai Pharmaceuticals Holding Co.,
Ltd was sentenced to death with a 2-year suspension of execution in 2011. In

the trial, he confessed that he helped Yang Jie to get Lantigens sole agency
and reached a total sales volume of over 10 million Yuan. In order to thank
Wu, Yang bribed him 6 times with 1.99 million Yuan, as well as 10 thousand US
dollars.
In 2007, Lantigen was included into Chinese children vaccination system
by Chinese Center for Disease Control and Prevention, and was listed in the
pull down menu of category II vaccines. The procurement right of category II
vaccine lies in the local CDCs. Since then, local CDCs have begun to use
Lantigen as vaccine.
Some local CDCs argued that Lantigen was listed under the vaccine
management system, so it could be interpreted as the state permission to
purchase and use.
However, Yu Jingjin noted that one of the functions of vaccine information
management system for children is to collect the using data of biological
products in China. Adding Lantigen into the system doesnt mean it is a
vaccine.
A person from National Immunization Program of Chinese Centre for
Disease and Prevention, who is responsible for this management system, also
re-emphasized that putting Lantigen into the system doesnt mean it is a
vaccine.

However, this argument also raised controversy. What is this system for,
the data collection or guidance for the local CDC? The official response
confused the two notions. One local CDC staff expressed his confusion; if it is
just for data collection, then why share it on a nationwide platform?

After it won the open tendering by Chinese Center for Disease Control and
Prevention in 2005, Jin Wei Xin Information Technology developed the
management system. People from this company told Caijing Magazine that,
Jin Wei Xin Information Technology was responsible for the technology,
operation and maintenance of the system, and also used to add or delete
some vaccine items. However, it can only be operated when authorized and
given the official issued files from Chinese Center for Disease Control and
Prevention.
Besides, Chinese Center for Disease Control and Prevention is very careful
with collecting usage data, and timely made corrections when problems
occurred. The basic information like product approvals, clinical trial data, and
indications will be examined on a timely basis. And for the procedure, it has to
checked and signed by departments from lower level to higher level within the
Center, and it will be assessed by the expert committee finally.
Obviously there must be some subjective intentions or objective
negligence in the process of adjusting the system menu. In a word, loose
management led to the loophole, one insider pointed out.
Yu Jingjin stated that the system has been adjusted in 2014, and Lantigen
was removed from the list. However, one local CDC staff told Caijing that
Lantigen was still in the system as a bacteria solute disguised with a new
Chinese name.
NHFPC has admitted that Lantigen is not a vaccine; manufacturers and

local CDCs should not refer Lantigen to vaccine in promotions, and those who
violated should be investigated. To prevent Lantigen from returning to disease
control system, NHFPC should also notify all CDCs not to use Lantigen in the
future, Yu also pointed out.

Whether involved in commercial bribery?

The Regulation on Vaccine Circulation and Vaccination, issued and
implemented in 2005 by the State Council, rules that vaccine production and
selling companies should provide qualified inspection or a copy of approved
certificate issued by Drug Administration Department of China, and company
importing vaccines should also provide a copy of the customs clearance of its
medical products.
CDCs and other vaccination organizations should ask for certificates when
receiving or purchasing vaccines, and keep vaccines at least for 2 years after
expiration, in case of future inspection.
The above mentioned staffs from local CDC judged that, the local affiliates
could easily discovered Lantigen is not a vaccine; and according to the
Regulation on Vaccine Circulation and Vaccination, vaccines should be
transported and kept using specialized cold chain, while Lantigen, as a kind of
drug, cannot be stored in that method, and this might trigger suspicion.
However, this fundamental mistake has been existed for years because of the
lack of legislations, people were chasing for profits though purchasing and
selling.
Several local vaccination organizations in Beijing, Liaoning, Gansu, and
Hunan provinces, told Caijing Magazine that Lantigen was unified purchased
by provincial CDC, and then transported to municipal and district level, and
transferred to the vaccination base department in the end. This procedure
applies with the Regulation on Vaccine Circulation and Vaccination. Besides
the unified procurement of provincial CDC, Caijing found out that, another
circulation channel of Lantigen is the sales representative employed by local
agents; they will directly sell Lantigen to vaccination base departments.

For example, Lanzhou Huawei of pharmaceutical and biological products

Co., LTD(Huawei), was a secondary agent of Lantigen in Gansu Province,
bought from the sole agent, Yu Shu Feng Pharmaceutical Co., Ltd.
There are two sales channels, one is CDC and the other is the vaccination
base in community hospital, people from Huawei added. The latter one is
also called extracorporeal circulation in pharmacies; this sales channel is
strictly prohibited because of the lack of supervision, which might lead to
safety risks.
As a new vaccine, Lantigen has a various timetable of in China.
According to incomplete statistics from reporters of Caijing Magazine, Hebei
Province was the earliest; Lantigen entered Shi Jiazhuang, the capital of
Hebei, in November 2009. It was introduced into Hei Longjiang Province in
September 2010, and to Shandong, Yunnan, Sichuan, Gansu in 2012. Up till
now, only Shanghai and a very few provinces has never sold Lantigen.
Jiangsu provincial CDC consumed the most Lantigen, with tens of
thousand doses each month. One former Lantigen agent mentioned, at the
country level, Beijing just consumed several thousand doses a month, the

numbers are even less in not-so-developed regions of China.

After scandal of Wu Jianwen, people from several companies involved
were handled separately, bu sales of the Lantigen from Yu Shu Feng
Pharmaceutical Co., Ltd was not affected. According to the statistics from its
recruiting web, the total sales volume of Lantigen in China has maintained an
annual growth as high as 200%; the total sales approached 600 million Yuan.
The retail price of Lantigen has jumped from 188 Yuan in the earliest
hospital channel to 298-398 Yuan at the vaccination department nationwide.
According to the media report, the retail price in Italy was only 14.2 Euro (90
Yuan).
The success of the national market by Lantigen should be attributed to
the blanket marketing strategy by secondary agents in each provinces.
Beijing Yitongkaiding Biology technology Development Co. Ltd was a Lantigen
agent in the Capital of China. The very first requirement of vaccine sales
representative is to promote products to the vaccination base department,
ensure targets are fulfilled or over fulfilled, follow the company requirement to
visit clients and do promotional works, attend the activities organized by
marketing department and continuously improve product awareness and
market share, according to its online recruiting pages.
The reporters of Caijing Magazine learned that company adopted the
small profits but quick turnover strategy in the terminal link by non-stop
visits to clients, and all circulation links can make their own profits.

According to industry insiders, taking the provincial CDC departments

unified purchasing standard as an example, the retail price of Lantigen is
slightly above 300 Yuan and its profit sharing system can be listed as follows:
the purchasing cost is less than 100 Yuan and the regional agents would profit
another 100 Yuan; The transparent and reasonable price difference, from the
unified purchasing price of the provincial CDC to retail price in the market, is
about 100 Yuan (often counted as transportation and labor cost, etc., the retail
price is determined by the local price control authorities).
In some areas of Beijing, Lantigen was charged from 322 to 398 Yuan per
dose. And the profit the doctor can make in the end was adjusted to 30 from
50 Yuan per dose. Those profits are so-called rebate sales in the industry.
In Qiu Lufengs eyes, the price differences between the retail price set by
price control authorities and the actual purchasing price of CDCs through legal
channels are deemed as legal profits. Nevertheless, manufacturers or agents
who rebate terminal links are suspected of offering commercial bribes, which
is against the Law of against Unfair Competition in which says A business
operator shall not resort to bribery by offering money or goods or by any
other means, in selling or purchasing commodities. And it also violates the
Pharmaceutical Administration Law of PRC.

The reporters of Caijing Magazine exclusively learned that Lantigen has

recently changed its sole agency in China again, and the new holder is
Cardinal Health, one of the biggest pharmaceutical distributors in America and
top 100 companies worldwide. Cardinal Health entered China in 1993, and
now it has become a large wholesale and marketing company in imported
drugs over China. Cardinal Health has shifted the sole agency of Lantigen to
Guangzhou Baiji Xinte pharmaceutical chain Co., ltd, a newly subsidiary

acquired in 2013.
One people from Guangzhou Baiji Xinte pharmaceutical chain co., Ltd
said, this company owns over 10 franchised pharmacies in China. But
Lantigen is exclusively sold in Beijing Baiji Xinte Pharmaceutical store,
whether Lantigen will be sold nationwide or whether new distribution model
will be developed still rest on the marketing plans of the company.

Who should be blamed at?

The medical staff driven by interests and even the sales persons who
pretend to be manufacturer should be blamed. Li Fei, citizen of Shenyang,
clearly remembered the health care doctor stressed that Lantigen can
effectively prevent Hand-foot-mouth disease (HFMD) 3 years ago. HFMD was
in its peak period at that time, we are so panic to paid for it without a second
thought. HFMD is an exanthematous infectious disease, which is totally
different from indication of respiratory infections of Lantigen.
Qiu Lufeng noted that sneaking Lantigen as vaccines will harm public
interests and vaccination-takers rights to know. If Lantigen is sold in hospitals
and drug stores, consumers might have similar products to choose from at
least. If listed as a vaccine, it is quite easy to win trust among vaccinationtakers, inducing them to use, as well as confusing it with real vaccine.
They make parents believing Lantigen a real vaccine and should pay for
it. Said Song Hualin a professor in Naikai University School of Law. These
tricks have changed the public expectations, and constitute an infringement
of public interests. At the same time, it might lead to abuse of drugs, even
overtreatment.
Vaccine Regulation defines vaccine as biological products used on
humans to prevent and control the occurrence and spread of infectious
diseases.
The interviewed law experts think that Lantigen is a kind of biological
product for treatment while its indications are not targeted at infectious
diseases; further more, it is circulated according to the Vaccine Regulations. In
terms of law, it is against this regulation and is also in suspicion of the
following violations of laws and regulations.
First of all, faking vaccine might constitute administrative illegality and
administrative authorities can fine the involved companies and order them to
rectify.
Second, it is suspected in violation of selling fake and unqualified drugs
according to The Drug Administration Law of PRC. Qiu Lufeng said, This
requires the involvement of judicial authorities to investigate and identify.
Third, from civil infringement aspect, if death or injuries happen, the
vaccination-takers can claim compensation from vaccination providers and
drug manufacturers.

Fourth, rebate selling is in suspicion of commercial bribery. From the

current situation, the Italy Lantigen manufacturer has shifted the legal risks to
its Chines agents. The agents of Lantigen in China constitute administrative
illegality as well as suspected criminal offense. One is commercial bribery,

and another one is selling fake vaccine, those two might involve criminal
charges.
Whether to accuse the Italy manufacturer depends on if it acknowledge of
the behaviors of its agents in China. If it does and not take measures to stop
these behaviors, Chinese judicial authorities will investigate with it and
ascertain its responsibilities under long arm jurisdiction.
Lantigen Scandal exposed serious loophole in the administrative system
of CDC. Qiu Lufeng and Li Dun, professor of School of Politics and
Management of Tsinghua University and executive director of Institute for
Social Policy, as well as other professionals, believe this loophole should be
fixed in time, otherwise the consequences will be unimaginable if other
products related to Childrens health sneak into the vaccine system.
Correspondent Cao Kai also contributed to this report.