High Noon for dodgy drug trials: China cracks down (again) on pharmaceutical data fraud

by MICHAEL WOODHEAD
Eight years ago, the Chinese government took a rather drastic step to clean up fraud and corruption in its drug regulator - it shot the director of the State Food and Drug Administration. However, this has  now been shown to be just another example of the uselessness of capital punishment as a deterrent, because the Chinese government has now announced ANOTHER crackdown on pharmaceutical drug registration fraud.

Although not spelling it out as such, the Chinese ministry of health has basically admitted that there has been ongoing and widespread clinical trial fraud since 2008. Not exactly a ringing endorsement for the succesors to the hapless Zheng Xiaoyu (above).

Despite efforts to correct the situation, the new director of the China FDA, Bi Jingquan (in office since 2015) has announced that the problems of clinical trial fraud have not been fixed. On 22 July he issued proclamation 117, which states that the China FDA is to review the registration applications for more than 1600 drugs, to verify the data as genuine. In a sign of how bad things are, the China FDA has described this as a "last chance amnesty" for all the naughty companies who have submitted false data to come clean. Leniency for those who confess ... and for those who don't - three years exiled in the wilderness. Yes, the China FDA is going to blacklist the drugs and companies that are found to have acted fraudulently - if they don't put their hands up and admit to it. They will be banned from re-submitting any drug registration applications for at least three years.

Not surprisingly, the pharmaceutical industry is not happy with this situation. In fact, they are shitting bricks and calling it "7-22" - the industry's play on 9-11. They know the government means business this time because of what happened to GSK - the Anglo-US company was fined a whopping 3 billion yuan ($489 million) for dodgy goings on within its sales force.

But to be fair on Big Pharma, it's not all their fault. The real villains are the so-called Clinical Research Organisations (CROs), which are agencies that actually do most of the local clinical trial work on behalf of the pharma companies. According to Caixin magazine, industry insiders acknowledge that the CRO sector in China is riven by fraud and corruption. Pharma companies pay the CROs to obtain the clinical trial data for China and submit it to the regulators. However, it's an open secret that the trials allegedly run in China's hospitals have been fixed or faked,  and the regulators bribed or blindsided.

To use the words of a regulatory agency insider, "the chaos has not been effectively curbed" since 2008 and therefore the CROs are being invited to undergo a period of "self examination" and verification of their results. The China FDA is tearing up its 2001 guidelines for drug registration and is starting afresh with more rigorous rules. The CROs have a chance to correct their irregularities or will be banished for three years. It is hope the shake-up will clean out what it currently a rotten and severely compromised sector - but this remains to be seen.

The last word goes to an insider at a reputable company - he says the short term effect may well be a kick up the arse for the CROs and the pharma industry, but old habits die hard. He says the only way to achieve positive long term change is to overhaul the management of CROs and pharma companies - and build expertise based on technical and scientific ability, not an ability to bend the rules

The previous head of the China FDA was shot for corruption - now his replacement is also in trouble

Former FDA chief Zheng Xiaoyu sentenced to death in 2007

by Michael Woodhead
Strange goings on at the China Food and Drug Administration. The top leaders past and present are facing public criticism for alleged corruption around the national pharmacopeia. 
There is a possibility that this bizarre case is a veiled way for the Xi Jinping administration to remove a senior official. There again, it might all be true.

The allegations relate to changes made to the official classification of the herbal remedy honeysuckle to favour producers in the Shandong hometown region of Shao Mingli, who recently stood down as FDA director. The claims are being made by an obscure provincial Party official from Hunan, who posted on his Weibo account that former FDA director amended the Chinese Pharmacopoeia to favour the use honeysuckle from his hometown area of north China, which resulted in south China producers losing business.

According to Shanghai Daily, the minor official, who is a member of the local disciplinary committee, says he has gone public because his private complaints were ignored. He claims the Pharmacopoeia Commission under the control of Shao Mingli changed the official terminology so that only plants from Shandong Province, where Shao comes from, could be used in herbal remedies.

The 'whistleblower' says he simply wants to see southern honeysuckle restored to official status so that southern China growers could resume their business. However, as well as calling Shao Mingli 'the major culprit', the official has also implicated other senior FDA officials and has called for the current director of the FDA, Zhang Yong, to step down as he has been obstructive and failed to act on the concerns of officials in southern Chinese provinces.

This might all be taken as a minor business dispute but for the fact that reports of the claims are being reportedly prominently in official media. If the whistleblower's claims are accepted as true this would lead to a major purge of the FDA leadership. And as you may know, this isn't the first time that the leadership of the China FDA have been in serious trouble. The accused Shao Mingli's predecessor Zheng Xiaoyu was executed in 2007 after being found guilty of accepting bribes in return for listing medicines.

According to the official FDA website, the current director Zhang Yong has addressed the claims and made a report to the Party Central Commission for Discipline Inspection. Is this a sign of China's greater openness and accountability? Or is it a Machiavellian way for the new Xi Jinping leadership to take out the leadership of the national drug regulator and replace them with their own people? I doubt that anyone will face the firing squad this time. Some powerful FDA figures may lose their positions, or this may simply be a way of putting them on notice and showing them who is the boss. It may all come to nothing.

Whichever is true, it seem that being head of the FDA in China is a very dangerous career move.

HPV vaccine delay | Baidu medical fraud | Malaria system success | Gassers in short supply | GSK case won't stop bribery

1. China may be delaying approval of HPV vaccines made by foreign companies until the country has a homegrown competitor, according to Global Times. The HPV vaccines Gardasil and Cervarix are still not available in China despite 30,000 women dying in China every year of HPV-related cervical cancer. Some Chinese doctors and officials claim there are ethnic differences in vaccine responses between Chinese and Europeans, and clinical trials that in Chinese people are needed to ensure of the vaccines' safety and efficiency on Chinese.

2.  Baidu earns its fortune by promoting fraudulent medical information at the cost of health and even lives, critics say. The search engine site is the main avenue used by illegal drug manufacturers and illegal hospitals to advertise in China, they claim. Many drugs that are explicitly banned by the China Food and Drug Administration (CFDA) are still on promotion on Baidu, an article in Daily Kos says.

3. A '1-3-7' system of dealing with malaria cases that is very successful and could be a model for other countries, researchers from the Jiangsu Institute of Parasitic Diseases claim. The system is based on case reporting within one day, case investigation within three days. and focus investigation and action within seven days.Since the system was implemented in 2012 the proportion of cases investigated in 3 days has reached 100%, and seven-day action rates are 50% and rising.

4. China has a shortage of 200,000 anesthesiologists as doctors avoid the speciality due to low salaries, heavy workloads and lack of a strong training system, experts say. A conference was told that China has only 100,000 anesthesiologists but needs 300,000. Eight anesthesiologists died of overwork last year, according to Yu Weifeng, head of the anaesthesiologist branch of the Chinese Medical Doctors Association.

5. A cure for the endemic corruption in China's healthcare system is still far away despite the scare campaign against executives of British pharma company GSK, the online magazine Caixin says. While the crackdown makes the authorities look like they are being tough on bribery for prescribing, the reality is that doctors still accept commissions and there is no fix for the 'demand side' of the bribery equation, the magazine says. The health ministry cannot afford to alienate doctors, who are central to the problem, it concludes.

Today's Top 10 China medical news stories

1. China is to launch a national cervical cancer screening program to test 10 million Chinese women annually, the National Health and Family Planning Commission says. The move follows concerns about increasing rates of cervical cancer, especially in women under 35. China has 130,000 new cervical cancer cases a year and up to 30,000 deaths a year due to the disease.

2. Vaccination rates have fallen as much as 30% since the hepatitis B vaccine safety scare over the deaths of 17 infants, immunisation experts say. They said the drop in vaccination rates could put up to 500,000 infants at risk of serious vaccine-preventable diseases.

3. In a landmark study, Shanghai clinicians have shown that pulse oximetry is a simple and accurate method for detecting major congenital heart disease in newborn babies in China. Writing in the Lancet, they say the method should be used in all maternity hospitals.

4. Salmonella in China is becoming resistant to most antibiotics including ciprofloxacin, ceftriaxone and azithromycin, "posing huge threat to public health and infection control" say clinicians in the journal Antimicrobial Agents and Chemotherapy.

5. A Beijing doctor was punched by the husband of a pregnant woman who said the doctor had pinched her stomach and threatened to kill her. The woman admitted she had first cursed the doctor when she believed she had been ignored by him.

6. Seven leading hospitals in China have signed an alliance agreement to for a National Team to tackle difficult diseases.

7. Kindergartens in Beijing have been struck by the norovirus gastro bug and dozens of children are showing symptoms such as diarrhoea and vomiting.

8. Young Chinese people do not wish to pursue a career in the medical sector, as jobs in medical services were ranked lowest in a survey of desirable careers by recruitment site zhaopin.

9. Complaints about fake drugs and medical devices being sold online are the most frequent calls to the China Food and Drug Administration hotline.

10. Hospital clinics in Shanghai are overflowing with three-four hour waiting times and yet community clinics are sitting almost empty and 'general practitioners see few patients because the public has little confidence in the level of services provided, according to an article in China Daily.

Tuesday news: The US health model best for China | Food and drug police | SARS victims forgotten | HIV medication non-compliance | Womens' wrinkles vary by region

US healthcare model is the answer to China's problems
The answer to China's health problems is to follow the American model and encourage growth of the private health insurance industry, says an American academic. Harvard's Professor Martin Feldstein, a former economics adviser to Ronald Reagan, says China could boost the growth of private health companies by creating tax breaks for employers and people who pay into them. Expansion of health insurance would also lead to an increase in the provision of hospital services as private insurers will enter the market, Professor Feldstein told Jewish Business News. By encouraging the purchase of health insurance by individuals or employers, the Chinese government could reduce the current trend for household saving to pay for medical bills and free up funds to increase consumer spending, he said.

'Health police' to be set up to catch drug and food crooks
"Watch it, here come the health police ..." - may soon become reality in China.  The Ministry of Public Security is planning to set up a new police division to deal with "food and drug safety crimes" in conjunction with the China Food and Drug Administration (CFDA). At present those who break food and drug regulations are supposed to be dealt with by the CFDA, but  the agency has weak powers and not enough staff to deal with the numerous cases of drug and food violations. The new food and drug police would have more powers, but some people are warning that it will lead to duplication and will not deter back street drug factories or sub-standard food manufacturers.

SARS victims abandoned to ill health
Many of the 5000 people in China who were infected with SARS a decade ago are struggling today under a burden of severe long term complications, clinicians say. SARS victims feel forgotten and abandoned, with may having debilitating lung problems that stop them from working and earning a living, according to an article by Professor Xiang Yutao and colleagues of Capital Medical University in Beijing. Many people who had SARS  developed long term problems and disabilities due to the high dose steroid therapy they were given, according to Professor Xiang. However there is no social or financial support for the many people who need ongoing medical treatment, he says.

HIV patients stop taking their medicines
Antiretroviral medicines are provided free of charge to HIV positive people in China but despite this, many stop taking them, leading to high rates of treatment failure. A new study from Guangzhou of 813 HIV-infected adult 19% had recently missed taking their medication and 7% had had stopped their antiretrovirals for at least a month in the past year). Those most likely to stop tended to be male, living alone, poorly educated and to drink alcohol.

The women with the best skin in China live in ...
If you want beautiful skin, go live near the Yangtze - that's the conclusion of a study of women's skin quality in different areas of China. Dermatologists found that skin quality and appearance depended on the local climate - in the cold, dry smoggy climate of Beijing womens' skin tended to be dry and wrinkled, whereas in the hotter sub-tropical humidity Guangzhou women had finer wrinkles - but more greasy skin due to higher sebum content.  Cities such as Shanghai and Wuhan had a combination of high moisture and moderate temperatures and women's skin had more elasticity.

SFDA begins "five rectifications" campaign against dodgy medical devices

The China State Food and Drug Administration has embarked on a "five rectifications" campaign against sub-standard and fake medical devices such as catheters, condoms and contact lenses.
After a half year investigation into the medical devices sector, the SFDA has launched a campaign to crack down on illegal manufacture of medical devices, illegal sales, false claims and misuse of five kinds of medical products.
The "special action" will focus on areas such as disposable infusion equipment that is re-used such as single use catheters. It will also focus on the manufacture and sale of fake and sub-standard condoms, which is a major pirate industry in China. Other areas where illegal activity is rife include the sale of unlicensed cosmetic contact lenses, hearing aids, and diagnostic aids for diabetes and hypertension. Devices that claim to cure back pain and myopia will also be included.
Th SFDA says its crackdown will apply the severest penalties for anyone involved in manufacturing, selling and promotion of fake and substandard medical devices and also for those making false claims including the use of medical 'experts' and those who use the names of famous institutes to endorse such products.

Hepatitis B vaccine in China: the unanswered questions

Commentary by Michael Woodhead

The deaths of 17 Chinese infants reported as having have followed hepatitis B vaccination are a tragedy that needs to be be fully investigated. When the first deaths occurred, the suspicion lay with a vaccine made by Shenzhen BioKangtai, with reports that certain batches of the vaccine were linked to the deaths of newborns in several provinces who had received vaccines with the specific batch number. Matters then became confused when reports were made of deaths of infants who had received other vaccines, including one made by a company called Beijing Tiantan. In all, 17 deaths have been officially reported in relation to hepatitis B vaccine.
When the first deaths were reported, the China Food and Drug Administration (SFDA) and the National Health and Family Planning Commission (NHFPC) ordered a halt to the use of the Biokangtai vaccine in China's newborn vaccination program and an investigation into the vaccine used.

After a rapid investigation of less than two weeks it has been announced that no problems have been found with the batches of Biokangtai's vaccine reportedly involved in the deaths and adverse reactions. The SFDA has also found no problems in the manufacturing, storage, transport or injection of the vaccine. Nevertheless, manufacturing permissions have been suspended for the three major manufacturers of hepatitis B vaccine, on the grounds that their facilities had not met the new GMP criteria for vaccine prodiction that came into effect on 1 January.
Post-mortem investigations into the infant deaths have also excluded the vaccine in nine cases, so far, and the other eight cases are waiting for autopsy results. Thus the hepatitis B infant vaccination campaign has quickly been given the all clear by the various authorities, and this verdict has been endorsed by the local branch of the WHO. The WHO representative rightly pointed out that the hepatitis B program was based on a good vaccine and prevented many cases of diseases and death every year. However, the announcement about the vaccine being safe was met with anger from some of the families of the children who died, and there has been disbelief on online forums about the "all clear" verdict from netizens who have little faith in monitoring of safety and quality of foods and medicines in China.

Despite the endorsement of WHO, there are still areas of doubt and unanswered questions in relation to the safety of China's hepatitis B vaccine and other child vaccine programs. First of all, if a vaccine was not responsible for the infant deaths, what was or were the real causes? With millions of newborns being vaccinated it is statistically probable that some natural infant deaths will co-incide with the time of vaccination. But the reports of 17 deaths in association with hepatitis B vaccination require in-depth investigation. Another question is whether it is possible to confidently rule out the vaccine as a possible factor in the cause of death. The investigations into the child deaths and into the vaccine quality and usage were done very quickly, raising questions about how thorough and comprehensive they were. There was also little transparancy about the process.
By comparison, when a similar series of vaccine-linked adverse events was seen in Australian infants given flu vaccine in 2010, authorities followed this up with several major inquiries. One inquiry was overseen by an independent clinician who examined the timeliness and appropriateness of the responses to the events. A second inquiry looked at the systems in place to monitor vaccine adverse events. A third inquiry looked into the vaccine manufacturing and quality issues. These separate inquires continued for months and in one case extended for more than a year. They concluded that a manufacturing anomaly had caused the vaccine batch for that year to be more 'reactive' than usual and to provoke more adverse effects. As a result, flu vaccine made by this manufacturer was banned from use in children, while products from other manufacturers continued to be allowed to be used. The other inquiries found that vaccine event monitoring and responses could have been better, and that information sharing had been poor and could be improved.

The recommendations from these inquiries were accepted by the Australian government, which has started to implement new vaccine monitoring and oversight systems. China could learn much from the Australian response to a series of vaccine related adverse events, to improve vaccine safety monitoring and response systems and to improve transparency in the whole process.
A clear and open response on the issue is needed from the Chinese authorities to maintain confidence in the safety of vaccination programs for children. It is not enough to point out that 15 million children receive the hepatitis B vaccine each year with the vast majority showing no ill effects and that the vaccine program prevents millions of cases of severe illness and death. Given the previous food and drug quality safety scandals seen in China - and the lack of public faith in the responses from the authorities - it is not surprising that there is now a crisis of confidence in the quality of China's food and drug products. Let us hope that vaccines do not become like milk powder, with parents only having faith in imported foreign brands for their newborns.

China's top 3 hepatitis B vaccine makers ordered to stop production because of GMP failings

by Michael Woodhead
China's three major manufacturers of hepatitis B vaccine have been ordered to suspend production because they have failed to meet new stringent GMP criteria that came into effect in 1 January.
The order from the Chinese Food and Drug Administration (SFDA) applies to Shanzhen Biokangtai, whose hepatitis B vaccine has been linked to a string of deaths among newborns in recent weeks. It also applies to Dalian Hanxin and Tiantan Biologicals.
According to a report from Xinhua, the vaccine manufacturers knew in advance that they had to meet the new GMP criteria by 1 January but failed to do so. The report says the new GMP criteria apply to all aseptic manufacturing plants, of which there are 1319 in China. It says two thirds have already met the new GMP requirements and others are working towards them. However, the three hepatitis B vaccine manufatcurers have not met the criteria and have been told that any further products produced from 1 January will not be accepted for use in China.
The Xinhua report notes that the three manufacturers account for about 80% of hepatitis B vaccine producetion in China. other manufacturers such as Hualan and Huabei have achieved GMP licencing but produce only about 10% of the vaccine supplies.
The SFDA says new GMP criteria apply to all manufacturers, and they estimate that there are GMP-compliant manufacturers for all 171 essential medicines. Mannufacturers who have not yet met the criteria have stockplied supplies of essential medicines, Xinhua notes.
The SFDA empahises that the move is only a temporary suspension of manufacturing and it is not ordering the  manufacturers to shut down the production facilities. Production may be resumed once the manufacturers show they are meeting GMP requirement, the SFDA says.

Dodgy drug makers will be blacklisted in China

China will blacklist producers of illicit food, drugs, medical appliances and cosmetics, according to a draft regulation published on Thursday.
Information on producers who "have seriously violated laws and regulations concerning food, drugs, medical appliances and cosmetics management and received administrative penalties" will be made public through government websites, says the draft regulation, which was issued by the China Food and Drug Administration.

Baidu and government partner to combat fake medical information online

by Liau Qun Ying
Chinese search engine Baidu and the China State Food and Drug Administration (SFDA) have partnered to fight fake medical information online.
Baidu will display results from China State Food and Drug Administration in medicine-related searches.
A Sina Tech report Monday said SFDA opened up three major databases to Baidu, which will offer three new search functions for certified drugs, the wiki entry of a medicine's instruction manual, and certified Internet drug stores.
The three major databases SFDA allowed access to include the SFDA drug database which has information of about 180,000 local and important medicine, instruction manuals for 6,000 over-the-counter drugs and Chinese traditional medicine, and the database of Web sites certified to sell drugs online.
The report said users can search for information on drugs via Baidu using the medicine's brand or generic names, as well as approval number. The search results will include information from SFDA'S database.
In addition, when users search for online drug stores, Baidu will show a "certified" tag next to online stores which have been certified to sell drugs. SFDA's database of instruction manuals for medicine also will be included in Baidu's Wiki, the report added.
It noted that Baidu since 2010 had worked with various government organizations, including SDFA, to fight fake information online. The search giant said it busted 201 businesses promoting counterfeit drugs last year.
In 2011, Baidu and other Chinese search engines were slammed by a state television station which alleged the search engine promoted Web sites which offered counterfeit drugs.
Source: ZDNet