In a course of the showdown prior the Lower House elections in Japan on September 11th, the major political parties published their "manifests". The flavor of the foreign word has been used to increase the importance of those policy documents, what essentially are just party’s pledge.
Jouhoublog
Drug approvals and pharmaceutical affairs in Japan
03/02/07
In direct contrast to earlier posting, Tamiflu caught again the public attention - this time for far from envious reason.
Two recent incidents - juvenile suicides without any underlying social cause, were widely published in Japan, including extensive coverage in two consecutive nights on February 26 and 27, 2007 by the national TV broadcaster NHK. Undoubtedly, the interviews with broken relatives of the young victims should increase the public awareness and hence to make parents closely monitoring the treated children. Yet, the science behind the frightening cases in Japan is not revealed.
The holder of the Manufacturing and Sale Approval for Tamiflu in Japan is Chugai Seiyaku of the Roche group. The product was approved in two formulations in 2002, sold since then to millions and stocked for tens of millions. 
The world supply of Tamiflu is not unlimited, as Japan also uses the majority of the world’s Tamiflu supply for seasonal flu. Japan has used 24 million prescriptions - ca. four times more than the US. World-wide, since Tamiflu was first approved in 1999, 12 children under 16 years of age and taking the drug have died, and 32 have suffered “neuropsychiatric events” such as hallucinations, confusion, convulsions and brain inflammation. All the deaths and the vast majority of adverse events in children, also including skin rashes and sensitivity, have been reported in Japan, where Tamiflu has been most widely prescribed. For the fiscal 2006 year, the MHLW received 12.8 billion Yen in supplementary budget as 8 billions of which to be spent for Tamiflu (90%) and Relenza (10%).
Back in 2005, both FDA and EMEA held discussions to analyze the frightening side events observed in Japanese children, but concluded that the “increased reports of neuropsychiatric events in Japanese children are most likely related to an increased awareness of influenza-associated encephalopathy”, increased use of Tamiflu in Japan, and greater monitoring of adverse events.
Certainly, the voices that the exacerbated reactions to Tamiflu among Japanese pediatric patients may be related to ethic (pharmacogenomics?) cause are being heard, but still the overprescription theory rules.
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Technorati Tags: MHLW; Japanese regulatory affairs
The deaths of a number of juveniles exhibiting abnormal behavior after taking the antiviral drug Tamiflu have sparked growing concern in Japan, but the Ministry of Health, Labor and Welfare says there is no confirmation of any causal link between such behavior and the drug. A group whose members say they are victims of Tamiflu-induced brain symptoms said that even if such a link has not been confirmed, doctors should call patients’ attention to possible side effects when they administer Tamiflu, and parents should not take their eyes off children who have taken the drug. On Feb. 16 in Gamagori, Aichi Prefecture, a 14-year-old girl who lived with her family on the 10th floor of a condominium building fell to her death apparently after taking Tamiflu. The girl had not gone to school that day because she was ill, and a doctor prescribed Tamiflu for her in the morning. The prefectural police said she apparently climbed barefoot over a 1.3-meter-tall barrier in the outside corridor and fell to her death while the rest of the family was out. No suicide note was found, and a friend of the girl said, “She would never commit suicide.” A representative of the group, 49-year-old Haruhiko Nokiba, said that in 2004, his 17-year-old son walked onto a national highway shortly after taking Tamiflu and was killed by an oncoming vehicle. He also said two boys who fell to their deaths from condominiums in Aichi and Okayama prefectures in 2005 and last year, respectively, had also exhibited abnormal behavior after taking the drug, and he believes the actions were related to side effects. On Tuesday in Sendai, a 14-year-old boy fell from the 11th floor of a condominium after taking Tamiflu the day before and died. Police are continuing to investigate the circumstances.
A research team of the ministry carried out a survey covering about 2,800 people in Japan last November and said it found no evidence of a relationship between the drug and abnormal behavior. There was no such behavior among 54 Tamiflu-taking patients who had died as of the end of January this year since marketing of the drug began in February 2001, the ministry said.
Tamiflu is produced by Switzerland’s Roche healthcare group and imported by Chugai Pharmaceutical Co. of Tokyo. The drug, also known as oseltamivir phosphate, will curb the growth of A- and B-type flu viruses, and if taken within 48 hours of the start of symptoms, fever will go down and recovery is said to be a day earlier than other drugs. In May 2004, Chugai added “consciousness disorders and abnormal behaviors” to a column of side effects in an appended paper attached to Tamiflu, but the company said it is a precautionary measure. At this stage, there is no need to single out the possibility of abnormal behaviors,” a ministry official said. But Rokuro Hama, head of the Japan Institute of Pharmacovigilance in Osaka, said, “There is a problem in the research team’s data. As far as behaviors immediately after taking the drug are concerned, the ratio of exhibiting abnormal behavior is four times greater” than publicly reported.
The ministry team is now carrying out a fresh survey covering 10,000 people with the aim of completing the results by fall. “We really need to establish whether there is any causal relationship with Tamiflu,” said chief researcher Shumpei Yokota, a professor in the graduate school of Yokohama City University. Takashi Arai, 50, a resident of the city of Kyoto and a member of the group of victims, visited a ministry official last week and said, “In prescribing drugs, some doctors carefully explain but some others just ask if drugs are taken or not.” In 2005, Arai’s son, who was in junior high school at the time, temporarily became violent after taking Tamiflu. Arai wants doctors, medical facilities and institutions to provide full information on possible side effects of Tamiflu to patients before they take the drug. The government is currently building a stockpile of the drug as part of its preparedness against an epidemic of a new form of flu.
Quote from Kyodo News, Feb 28, 2007
A research team of the ministry carried out a survey covering about 2,800 people in Japan last November and said it found no evidence of a relationship between the drug and abnormal behavior. There was no such behavior among 54 Tamiflu-taking patients who had died as of the end of January this year since marketing of the drug began in February 2001, the ministry said.
Tamiflu is produced by Switzerland’s Roche healthcare group and imported by Chugai Pharmaceutical Co. of Tokyo. The drug, also known as oseltamivir phosphate, will curb the growth of A- and B-type flu viruses, and if taken within 48 hours of the start of symptoms, fever will go down and recovery is said to be a day earlier than other drugs. In May 2004, Chugai added “consciousness disorders and abnormal behaviors” to a column of side effects in an appended paper attached to Tamiflu, but the company said it is a precautionary measure. At this stage, there is no need to single out the possibility of abnormal behaviors,” a ministry official said. But Rokuro Hama, head of the Japan Institute of Pharmacovigilance in Osaka, said, “There is a problem in the research team’s data. As far as behaviors immediately after taking the drug are concerned, the ratio of exhibiting abnormal behavior is four times greater” than publicly reported.
The ministry team is now carrying out a fresh survey covering 10,000 people with the aim of completing the results by fall. “We really need to establish whether there is any causal relationship with Tamiflu,” said chief researcher Shumpei Yokota, a professor in the graduate school of Yokohama City University. Takashi Arai, 50, a resident of the city of Kyoto and a member of the group of victims, visited a ministry official last week and said, “In prescribing drugs, some doctors carefully explain but some others just ask if drugs are taken or not.” In 2005, Arai’s son, who was in junior high school at the time, temporarily became violent after taking Tamiflu. Arai wants doctors, medical facilities and institutions to provide full information on possible side effects of Tamiflu to patients before they take the drug. The government is currently building a stockpile of the drug as part of its preparedness against an epidemic of a new form of flu.
Quote from Kyodo News, Feb 28, 2007
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02/09/07
Split and re-launched
We are receiving on a daily basis numerous inquiries concerning the regulated medicinal products (drugs, quasi-drugs, medical devices and cosmetics) and the regulatory affairs in Japan. To further make world-wide available the researched answers we have provided to the professional users and customers, a new interactive repository - Recentanswers has been re-launched as a blog. The Recentanswers Blog is an enhanced Frequently Asked Question (FAQ) system covering most of the queries and questions sent to the Regulatory Department of the JKS and to JKS in general. The answers not only address the issues, but also are extended to provide wider background information.
In contrast to Recentanswers blog, our other forum - Jouhoublog is preserved for the personal opinions of researchers and analysts working in the regulatory and business development fields. A number of events in the Japanese pharma industry warrant comments, especially the regulatory and procedural news what are largely ignored by the commercial news services.
All users and customers are encouraged to send queries for regulatory and other pharma, biotech and medical device issues by email to regulatory@jouhoukoukai.com
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Technorati Tags: MHLW; Japanese regulatory affairs
01/20/07
In contrast to the chorused complains against the - as lobbyists put it - “glacier speed” of new drug approval in Japan, the chronology of Alimta shows quite the opposite. Let’s follow:
- In June 2005, it became clear that in addition to factory workers, many people living near the former factory operated by machinery maker Kubota Corp. in Hyogo Prefecture, had developed asbestos-related disorders, including malignant pleural mesothelioma. Soon similar health problems were reported in other areas such as Gifu and Nara prefectures. According to the statistics released by the Ministry of Health, Labor and Welfare, 7,924 people across the nation died of mesothelioma in the 11 years since 1995. Due to the difference in collecting the primary data in different prefecture, the actual number patients is thought to be higher and not expected to peak until 2030
- In the second half of 2005, the asbestos became a household word after an extensive coverage by the media. A package of bills aimed at providing financial support to people suffering from asbestos-linked diseases was enforced in 2006. According to the compensation scheme, the Government plans to collect 7.4 billion Yen within 4-year period starting 2007 to cover the compensation including treatment for victims and the affected families
- In November 2005, the Health, Labor and Welfare Ministry has decided to shorten the review period for a new drug to treat mesothelioma (Alimta) to one year form the average time of two years. Meanwhile, Nippon Eli Lily Japan KK has been conducting dose-finding trial from February and late Phase II trial from October 2005
- A submission for approval of Alimta in Japan was made on June 26, 2006 for treatment of malignant pleural mesothelioma in combination with cisplatin. On June 28, 2006 six manufacturers of cisplatin products applied for revision of “Indications” in the Package Inserts of theirs respective 6 products (in 10 formulations). The approval review was completed by December 7, 2006 and the Minister of Health, Labor and Welfare granted on January 4, 2007 a Manufacturing & Sale Approval to Alimta (vials 500 mg)
along the revised cisplatins. Overall, the review took only 5 months - In another speedy leg, Alimta has been given a reimbursement price
on January 19 and the company is planning to start the sales on January 22, 2007. Due to the limited pre-approval trials, as one condition for approval, the maker is obliged to recruit at lest 300 patients in Phase IV study. The drug will be initially introduced at around 400 hospitals nationwide specialized in chemotherapy
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12/03/06
One of the leading Japanese shosha (general trading company) announced that in 20:80 partnership with a large foreign biotech-oriented venture fund has set up a service company under the apt name JapanBridge.
In the past three decades, an untold number of "Japan-bridging" companies were planned, set up and even still existed by entrepreneurs from both sides of the Atlantic (in the spirit of full disclosure, those included some of our founders).
What should be made the new JapanBridge different aside from the 100 million US$ expected to be pumped into the new entity within 3 years? The current answer is the new formula - taking only late clinical stage compounds from early stage biotech companies.
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Technorati Tags: MHLW; Japanese regulatory affairs
02/12/06
If the approval of Iressa happened to be if not a cloud, but at least cloudy, it also has a silver lining. Both in response to the public criticism and along with the newer obligations concerning the pharmacovigilance, the authorities have decided to start disclosing information on advirse events (AEs) reported for medicines approved in Japan. Although it is hardly to assume that the disclosure step has been prompted solely by the Iressa saga, yet the reaching of Iressa incidents to the general public nonetheless served as a catalyst.
Remarkably, the AEs data - previously elusive even to professionals, are now readily open to the public. Many pharmaceutical companies in Japan have fallen to third party providers to make available even for professional audience - such as physicians and pharmacists, and even the most innocent pieces of information - such as photographs of the packages, against charges and detailed registration. The Government took an opposite approach to have all the data posted at no charge and accessible without any tracking. Commendable.
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Web site to offer information on drug side effectsThe Pharmaceutical and Medical Devices Agency on Tuesday launched a Web site that enables people to search for lists of side effects, symptoms and associated diseases brought on by a variety of medicines. The site, www.info.pmda.go.jp, includes a database of all side effects as reported by drug manufacturers. The first data to be made public by the agency was in April 2004, with accounts detailing 732 medicinal products and 2,477 related case studies that include information such as age, gender, disease, details of the side effects, the drug and other medicines taken concurrently. The site also includes case studies for the 63 people whose deaths during that period were brought on by side effects from medicines they were taking. Twelve of these deaths were linked to the lung cancer drug gefitinib, marketed as Iressa. Warnings also are included for cases in which the side effects were found to not be connected to health problems. The PMDA will make information from May 2004 onward available in due course, aiming to put a system into effect before the end of March 2008, with updates every six months. Until now, such reports were limited to cases involving previously unknown side effects, or where revisions had been made to warnings over usage. The new system was conceived of in the face of increasing complaints from citizens’ groups and others organizations demanding all the information be made public, as only 1,872 of the 25,000 or so drug-related side effects last fiscal year had been disclosed. The agency, an independent organization, has also begun posting on its Web site easy-to-understand explanations on dosage and side effects. Beginning with 54 kinds of drugs, including oral diabetes medication, the next medicines to be posted will include antirheumatic and antiasthmatic drugs. (The Daily Yomiuri, February 9, 2006, p. 3)
12/02/05
Femara - an aromatase inhibitor - is known to be submitted and currently under a review by the Japanese regulatory authorities. Yet, as distributed today by the mass media, the warnings issued by Novartis AG were forwarded to the physicians in Japan as well. As read between the lines - under the provision of the Pharmaceutical Affairs Law (PAL), any unapproved drug could be imported for individual use in Japan as long as the custom official is shown a prescription by Japanese doctor. Obviously, Femara (the name is misspelled in the original news release below) - another of the unapproved anti-cancer drugs in Japan has been imported by significant number of female patients treated domestically.
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Swiss firm warns breast cancer drug can harm unborn children
Thursday, December 1, 2005 at 07:15 JST
TOKYO — A Swiss pharmaceutical company has decided to warn gynecologists in the United States, Japan and other countries not to prescribe women a breast cancer drug during pregnancy or before menopause, as it may harm unborn children, officials of the its Japanese associate said Wednesday.
TOKYO — A Swiss pharmaceutical company has decided to warn gynecologists in the United States, Japan and other countries not to prescribe women a breast cancer drug during pregnancy or before menopause, as it may harm unborn children, officials of the its Japanese associate said Wednesday.
Letrozole, distributed by Novartis AG under the name Femera, is commonly used to prevent relapses of breast cancer. Animal tests have proven that the drug can cause fetal abnormalities and its use in pregnant and pre-menopausal women has been banned.
11/25/05
In Japan the Pharmaceutical Affairs Law (PAL) permits individual import of both approved and unapproved drugs, as long as you have a prescription from Japanese physician.
Should we expect the Tamiflu to crash this winter the previous individual import record of Thalidomide (reportedly about 500,000 tablets were imported before the approval)?
Tamiflu is sold in Japan in two formulations: 75 mg capsules and 3% dry syrup, as the cost for 1-day treatment is 727.4 Yen for capsules and 1,392.5 Yen for the syrup.
Reported below in Yomiuri Shimbun:
Shortages push Tamiflu prices up 10-fold
Online purchases have depleted stocks. One agent offers 10 capsules of Tamiflu, or oseltamivir, imported from the United States for 30,000 yen, excluding shipping charges. "One U.S. company recently told us the price had risen to more than 300 dollars. We need to raise ours to 38,000 yen just to show a profit," the company’s president said. According to the company, which has acted as an import agent for six years, demand for Tamiflu remained low until last year when 10 capsules could be obtained for 8,000 yen. The government in 2001 designated the drug to be covered by national health insurance.
Purchase orders for Tamiflu surged early this month following an increase in news reports on the spread of a new type of influenza and the government’s announcement of its plan to further stockpile the flu-fighting drug. The company received orders for about 20 sets in the past week. Another agent, which offers Tamiflu for 25,000 yen, said it was out of stock and had a waiting list of about 100 people.
Chugai Pharmaceutical Co., which imports and markets Tamiflu, prices the drug at 363.7 yen per capsule. A dosage of two capsules a day is normally recommended for five days, and a set of 10 capsules is offered at 3,637 yen. Insurance coverage reduces the price to about 1,100 yen, but it requires a doctor’s prescription, which increases to the total cost to about 3,000 yen.
(Nov. 24, 2005)
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Technorati Tags: MHLW; Japanese regulatory affairs
11/03/05
In a rare PR move, the MHLW made publicly available through the mass media the previously adopted decision regarding changes in the approval qualification for anticancer drugs. Today Kyodo News Agency distributed in bilingual format the announcement that from April 1, 2006 the NDAs for anticancer drugs should include - along with the efficacy and safety profiles, data proving prolongation of patient life. Yet another of the Iressa aftershocks…
The new guideline from MHLW stipulates that data from Phase III studies in patients with non-small cell lung, stomach, large intestine and breast cancer should contain detailed evidences for life prolongation.
Ironically, Iressa (gefitinib) was one of the very few New Chemical Entities (NCE) to be first internationally approved in Japan and it turned into a regulator’s nightmare, as the cases of fatal interstitial pneumonia reached to the tabloids. Ever since the first news about lethal side effects of Iressa appeared in 2002, the MHLW found itself between rock and hard place: criticized for both negligence in "hastily" approving Iressa and systematically failing to approve other advanced anticancers.
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09/13/05
We are receiving periodically inquiries regarding "quasi-drugs" in Japan, including about one recently mentioned. "Quasi-drugs" are the second category among all regulated medicinal products in Japan (along with drugs, medical devices and cosmetics).
It is not clear how and when the term emerged, however the origin could be traced to the first translations in 1980s of the Pharmaceutical Affairs Law (Law).
Current dictionaries only add to the confusion. English dictionaries define "quasi-" as resembling to some degree. On the other hand, the original Japanese term (iyaku gaibuhin) implies a drug used "outside" (i.e. not to be digested or injected). Bilingual (translation) dictionaries are even more helpless giving the meaning of iyaku gaibuhin as over-the-counter drug, unregulated drug (?!) and even the bizarre interpretation of AltaVista as "medicine public item".
Neither is correct. Quasi-drugs are regulated products, sold with no prescription and thus falling, although not filling up the OTC category. The category of quasi-drugs now covers much more types of products than the classical quasi-drugs (for foul body odor and breath control, hair removal, body pests extermination). The PAL in Article 2 defines quasi-drugs as not equipment or instruments and having no more than a mild effect on the human body.
The aromatic anti-Legionella cleanser for bathtubs may fit well into the definition, but how about the growing line of dietic products labeled as quasi-drugs?
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Technorati Tags: MHLW; Japanese regulatory affairs
08/28/05
Such pledges - more or less vague, have been around for years, however recently they sharpened to include more numerical targets and to reflect real needs of Japan. Such as the growing cancer epidemic. In a quite telling move, the Democratic Party of Japan (Minshuto) announced its manifest from August 16 that if won, would allocate 50-fold more funds (in the range of half billion dollars) only for anti-cancer measures. Among the major problems of economy underperformance and pension reform, it is rare a specific healthcare point of concern to earn such attention. To certain degree this is a reflection of DPJ membership - the only party to point on having physicians in its ranks.
Yet, there is no word about the sensitive point of new drug approvals. Perhaps, the last time when pharmaceutical issues gained higher visibility was in June 1998 when the Subcommittee on State Pharmaceutical Policy, belonging to the Research Committee on Basic Medical Policies of the ruling Liberal Democratic Party (LDP) published a policy report outlining the party’s vision on the government – pharmaceutical industry collaboration.
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08/10/05
Recently, FDA updated the labeling of the three leading oral erectile dysfunction (ED) medications (Cialis, Levitra and Viagra) with a warning about the sudden vision loss, attributed to NAION (non arteritic ischemic optic neuropathy). While such updates are fairly common in the post-marketing period of any drug, in the case of Viagra it brought to the surface some information not very willingly disclosed by its maker. In the efforts to downplay the significance of NAION incidence, Pfizer reported that by mid-2005 a total of 27 million men have taken safely Viagra…
That’s it! For full seven years since the launch in 1998, Viagra has been used by only 1% of the world’s male population. Is this more, or less or in the range of what has been expected? Given the massive advertising campaign (over 100 million US$ in US alone), the unprecedented public interest and brand awareness, the common belief was - and likely still is, that Viagra is already taken virtually by everybody.
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Technorati Tags: MHLW; Japanese regulatory affairs
08/06/05
One of the very prompt questions following the Eril mystique posting asked about www.eril.jp.
Against all educated guesses, it turned out not to be a product site of Asahi Kasei. It is online shop of small distributor of cosmetics, dieting and beauty goods, doing business as "Eril" and on the top of its catalog under number Eril ck01 is a product named "Hairless Milk". Should we mention it here? Whatever hideous, the "Hairless Milk" is approved by MHLW in Japan as quasi-drug, otherwise there are no relations with cardiovascular Eril. But what about the 17-old trademark?
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08/05/05
Since 2001 we have received dozens of inquires about Eril. Surprising is also the span of the inquirers – from US testing laboratories to product developers in EU to university researchers. Why Eril?
Eril (fasudil hydrochloride hydrate) was discovered by Asahi Kasei KK in 1980s. It is absolutely impossible to decipher the name of Eril, even knowing the typical for those years penchant for cryptic and “meaningful” abbreviations. The name of the pharmaceutical form Eril Inj. S stands for: Epoch-making relaxant for ischemic locality Injections Sun. Obviously afraid that somebody else might come with the same pearl, the maker registered Eril as a trademark 
in 1988 – more than ten years before the approval and much earlier before the clinical trials ever began. The picture on the left is the actual image deposited to the Japan Patent Office.
Eril was licensed out in 2001 to Schering AG for development of antiangina oral formulation - it was then when the interest started to flow together with requests for samples of the compound and information. Both are scarce, particularly the latter. Unlike the medicinal products approved in Japan after the enforcement in 2001 of the Public Access to Information Law (PAIL), neither the Approval Review, nor the Summary Basis of Approval (SBA) are publicly available. Yes, the Package Insert – in its 7th revision from April 2005 made to conform to the amended Pharmaceuticals Affairs Law (PAL) is obtainable, however all other known documents – Drug Profile, Interview Form (a predecessor in Japan of the SBA), Pharmacopoeial Information are only accessible through a members-only commercial third party.
Eril is rarely advertized and for an epoch-making product sells somewhat weakly in Japan – chalking at average 10-12 millions US$ annually. But the inquiries keep coming…
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Technorati Tags: MHLW; Japanese regulatory affairs
08/03/05
Quite a few of our customers are trying to use the search engine of the www.jouhoukoukai.com web site to retrieve Japanese regulatory documents. Recently, a user queried the site for a particular document until exhausted all possible syntax combinations:
- notification no 1831
- "notification no 1831"
- "notification 1831"
- +notification +no +1831
- "notification no. 1831"
The search has ended with “not found” but not because of the information regarding the “Notification No. 1831” is not available or the queries were not diligent. Until 2000 the Pharmaceutical Affairs Bureau (PAB) and its successors from 1997 - the Pharmaceutical and Medical Safety Bureau (PMSB), and from 2001 - the Pharmaceutical and Food Safety Bureau (PFSB) simply numbered the released documents in order of issuing what resulted in non-descriptive document numbers such as “1831”, and hence now there are two – completely unrelated documents under one and the same number (1831) and distinguished only by the title and date of issue. The older PMSB/ELD Notification No. 1831 (dated December 17, 1999) is entitled “On the Guidelines Concerning Clinical Studies of Medicinal Products in Pediatric Group (draft)”, while the more recent one of December 27, 2000 is on “Revision of the Guideline for Timing of Preclinical Studies in Relation to Clinical Trials”.
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08/01/05
One of the unapproved anti-cancer products, recommended so far by the Committee for the Examination of the Use of Unapproved Medicinal Products for domestic development is thalidomide, which was once registered and in 1962 withdrawn in Japan. The task for clinical development with a sole indication for treatment of multiple myeloma is being undertaken by the Fujimoto Seiyaku KK. The Osaka-based company is small, discloses its staff (about 300), but not the revenues. Apparently, it is run in a very traditional way, so one may wonder how it will survive the PR barrage while developing the notorious compound. On July 20, 2005 in what it seemed as a rare press conference the Fujimoto’s management reported the progress in planning the clinical trials: IRBs of 22 hospitals accepted the protocol and the recruitment of patients through informed consent has started. However, the trials are amidst of a considerable controversy. While for years the Japanese branch of International Myeloma Foundation (IFM Japan) has lobbied for official registration (in contrary to private use legal import), the relatives of the 60s disaster victims are voicing strong concerns regarding the safety. Surprisingly or not, no references of any kind about thalidomide on the web site of Fujimoto have been posted.
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07/29/05
On January 8, 2004 the business press in Japan reported that the little known Division of Clinical Trial Design & Management to the Translational Research Center of Kyoto University Hospital has conducted a study on anti-cancer drugs in Japan. For this study the Division has utilized a very modest methodology by comparing the list of drugs classified as “anti-cancers” in the 2003 edition of the "Current Medical Diagnosis and Treatment” - an easy-to-read manual believed to be commonly used by the US physicians, to the medicinal products approved in Japan for treatment of cancer. In short, the conclusion pointed that 30% of anti-cancers and 40% of the products for complementary oncology therapy were not yet approved in Japan by the end of 2003.
Although reported in a highly sensational style – the title in the local English-language “The Daily Yomiuri” was “Japan bars 30% of drugs used in U.S. for cancer”, it remains unclear whether the Division actually ever published the results of the study (emails and calls to it were not returned).
Whether the publicizing the findings triggered the current flow of approvals of anticancers in Japan is debatable, however it came amid a growing tension between all players in the oncology healthcare in Japan. By early 2004 it was widely acknowledged that a number of patients have been using unapproved, but imported drugs or domestically approved but applied off-label products. In one of the most demonstrative cases, as many as 500,000 tablets of Thalidomide were imported legally in Japan by individual patients for treatment of multiple myeloma. None of the accompanying costs for the purchase, shipping and custom clearance were borne by insurers and no entity has been responsible for post-marketing surveillance. All players involved – patients, providers (practicing physicians), payers, pharmas and the regulators, were unhappy but an exit from the impasse came in late 2004 by reaching the Basic Agreement of December 15, 2004 between the Minister of Health, Labor and Welfare and the Minister of State in charge concerning so-called “Mixed payment for medical examination and treatment” – or a concurrent provision of insured and noninsured services and therapies.
As a first measure the MHLW established a working group called Committee for the Examination of the Use of Unapproved Medicinal Products (aka as Investigational Committee for Usage of Unapproved Drugs, both titles are provisional translations) which already has had five regular meetings. Full details of the system for development of unapproved drugs in Japan are included in the report of the 21st New Drug Evaluation Division Information Meeting (available online at http://www.jouhoukoukai.com/Merchant2/merchant.mvc?Screen=PROD&Product_Code=JM_I_017&Category_Code=JMI), but in brief, the authorities are asking the pharma makers to initiate clinical trials of new products or for new indications, by providing support and reducing the red tape. At the latest meeting held on July 22, 2005 the Committee adopted a recommendation for clinical development of four new products.
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Jouhoublog started as Askjouhou - a name now reserved for the JKS users forum.
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Technorati Tags: MHLW; Japanese regulatory affairs