- Email: [email protected]
Debate on doctors' working hours
Towards harmonisation
on
drug registration
The second International Conference on Harmonization of European, US, and
Japanese drug registration requirements revealed large gaps still needing to be bridged despite backing for three common guidelines, covering reproductive toxicity testing, stability, and inclusion of geriatric subjects in clinicals. At the meeting held in Orlando, Florida, last week, regulators were generally optimistic about the ICH process, with FDA Commissioner David
Kessler
declaring a common registration package "a realistic possibility" and the head of the EC Commission pharmaceuticals division Fernand Sauer announcing that he was "satisfied" with the way the process had moved since the first ICH conference in 1991 (ICH-1). However,
industry,
especially
European
drug
makers, claimed that progress was slow and that in some areas little had been achieved since ICH-1. The director general of the European Federation of Pharmaceutical Industry Associations, Nellie Baudrihaye, said that regulators were "moving in the right direction, but slowly" and that the parties were clearly not yet in a position to harmonise practices. ,
1 he
guideline
on
stability testing
in
particular spawned heated debate between European regulators and industry and the FDA. At the first ICH talks 2 years ago in Brussels, all partners had agreed in principle the shape that the guideline would take, but after a further 18 months of drafting work, the FDA threw out the planned text and demanded a rewrite. Baudrihaye attacked FDA’s stance during the conference opening plenary sessions, saying that 2 years’ work had been wasted and that European drug makers were disappointed the guideline was not closer to the original draft. European industry feels that the guideline (which the EC’s Committee for Proprietary Medicinal Products adopted last month) now more or less extends US requirements, particularly on storage conditions, to the EC and Japan rather than really harmonising the different rules into a compromise text. Under the guideline, long-term test requirements would mean drugs being stored at 25°C ± 2°C, with 60% relative humidity (RH) ±5% for a minimum of 12 months, and that for accelerated testing they should be kept at
:
40°C +2’C with 75% RH ±% for at least 6 months. However, when a drug substance fails to meet specifications during the accelerated testing, there must be additional testing at an intermediate condition such as 30°C ±2°C, 60% RH ±5%. For these products the initial application would have to include a minimum of 6 months’ data from an ongoing 1-year study at 30°C, 60% RH. Controversy also arose over a planned guideline on clinical studies, because the FDA refused to support the draft that the EC’s CPMP and European industry had co-authored. FDA wants to retain its own requirements and does not want to make the changes that the draft guideline would require, the Europeans complain. A subject close to Japanese heartsnamely, ethnic differences in drug evaluation-is to be further studied over the next 2 years in the run up to the ICH-3 talks in Yokohama. Ethnic differences, or the way different races react to various substances, could have a significant impact on efficacy questions such as the scope of the required safety data base and interpretation of dose-response data across
regions. Sara Lewis
patients who had died had been informed of be enacted remains uncertain. Whitehall continues to dispute the idea that the their diagnosis and 3 in 4 of the patients had not even been told what therapy they had European Community is entitled to treat received. With the growing number of such matters as health and safety issues under the Treaty of Rome. The matter may chemotherapy treatments, the possibility Distribution of a new antiviral drug introof their accidental prescription together yet end up in the European Court of duced in September has been temporarily with sorivudine had been anticipated; Justice. Meanwhile, Social Affairs Commissuspended by its manufacturer because of patients who have chemotherapy are often the drug’s association with deaths, believed are sioner in an immune suppressed state and so Padraig Flynn was given a rough ride to be due to its interaction with anti-cancer at the Parliament’s October session when for sorivudine. potential candidates : he was reluctant to take up the said the action taken the agents. Sorivudine, (+ )-l-&bgr;-D-arabino- : by he Apart from has uracil of Health the with. the Council of Ministers in an furanosyl-5-[(E)-2-bromovinyl manufacturer, cudgels Ministry is effort more concessions. Only an antiviral to to wrest order to refrain issued an (Usevir, Nippon Shoji), drug physicians of for treatment zoster. with when the It to from the developed assembly threatened to reject the herpes giving drug patients can be given orally and the product has a entire proposal did he agree to support unknown medication profiles and to people Strasbourg’s amendments-having warhighly selective inhibitory action that is : with histories of cancer. times that of ned that the entire directive might be lost. 50 approximately acyclovir. Over 500 000 tablets have already been sold Makato Yawata : Spokesman for the Social Affairs Comto 10 000 medical institutions in Japan. mittee, Belgian MEP Mr Raphael Before being put on the market, sorivuChanterie pinpointed the key amendments dine had been known to induce severe among the many being sought by MEPsleucopenia when used in combination with Debate on doctors’ working that the directive should include a "nonthe pyrimidine metabolism antagonist regression" clause to prevent member hours states using the EC legislation as a pretext fluorouracil, and a warning had been to water down existing national standards; printed with the instructions for use. that it should incorporate a specific referDespite this precaution, adverse effects ence to ILO standards and set out a British demands that junior doctors should were reported in the month after the reference period over which night work be denied protection under EC legislation introduction. There have been at least 7 on could be calculated; and that it should of to this and serious effects due holiday reports working hours, night work, drug have been condemned in 3 of the have the died. interaction; pay patients European create "a basic level of protection for as Parliament. British Labour MEP there have been claims that the Stephen many workers as possible", not provide Although said: "We can wonder at the were insufinstructions Hughes only exemptions for numerous occupations. drug warning Another sticking point concerned barbarity of the UK government negotiatficiently strong, a possible contributory factor could be the lack of informed patient implementation: members states would ing a clause to exclude junior doctors from have three years to transpose the directive the terms of the directive". He said it was consent in Japan. Sometimes patients on into national legislation and would then antitumour drugs do not know that they "reprehensible in the extreme" that the have seven years as an "opting out period". British authorities should be prepared to have cancer. According to a nationwide
Deaths due to drug interaction
survey conducted last year by the Ministry of Health and Welfare, only 18% of cancer
1166
put doctors’ health and that of their patients at risk. Whether the legislation will
Arthur
Rogers
on
drug registration
The second International Conference on Harmonization of European, US, and
Japanese drug registration requirements revealed large gaps still needing to be bridged despite backing for three common guidelines, covering reproductive toxicity testing, stability, and inclusion of geriatric subjects in clinicals. At the meeting held in Orlando, Florida, last week, regulators were generally optimistic about the ICH process, with FDA Commissioner David
Kessler
declaring a common registration package "a realistic possibility" and the head of the EC Commission pharmaceuticals division Fernand Sauer announcing that he was "satisfied" with the way the process had moved since the first ICH conference in 1991 (ICH-1). However,
industry,
especially
European
drug
makers, claimed that progress was slow and that in some areas little had been achieved since ICH-1. The director general of the European Federation of Pharmaceutical Industry Associations, Nellie Baudrihaye, said that regulators were "moving in the right direction, but slowly" and that the parties were clearly not yet in a position to harmonise practices. ,
1 he
guideline
on
stability testing
in
particular spawned heated debate between European regulators and industry and the FDA. At the first ICH talks 2 years ago in Brussels, all partners had agreed in principle the shape that the guideline would take, but after a further 18 months of drafting work, the FDA threw out the planned text and demanded a rewrite. Baudrihaye attacked FDA’s stance during the conference opening plenary sessions, saying that 2 years’ work had been wasted and that European drug makers were disappointed the guideline was not closer to the original draft. European industry feels that the guideline (which the EC’s Committee for Proprietary Medicinal Products adopted last month) now more or less extends US requirements, particularly on storage conditions, to the EC and Japan rather than really harmonising the different rules into a compromise text. Under the guideline, long-term test requirements would mean drugs being stored at 25°C ± 2°C, with 60% relative humidity (RH) ±5% for a minimum of 12 months, and that for accelerated testing they should be kept at
:
40°C +2’C with 75% RH ±% for at least 6 months. However, when a drug substance fails to meet specifications during the accelerated testing, there must be additional testing at an intermediate condition such as 30°C ±2°C, 60% RH ±5%. For these products the initial application would have to include a minimum of 6 months’ data from an ongoing 1-year study at 30°C, 60% RH. Controversy also arose over a planned guideline on clinical studies, because the FDA refused to support the draft that the EC’s CPMP and European industry had co-authored. FDA wants to retain its own requirements and does not want to make the changes that the draft guideline would require, the Europeans complain. A subject close to Japanese heartsnamely, ethnic differences in drug evaluation-is to be further studied over the next 2 years in the run up to the ICH-3 talks in Yokohama. Ethnic differences, or the way different races react to various substances, could have a significant impact on efficacy questions such as the scope of the required safety data base and interpretation of dose-response data across
regions. Sara Lewis
patients who had died had been informed of be enacted remains uncertain. Whitehall continues to dispute the idea that the their diagnosis and 3 in 4 of the patients had not even been told what therapy they had European Community is entitled to treat received. With the growing number of such matters as health and safety issues under the Treaty of Rome. The matter may chemotherapy treatments, the possibility Distribution of a new antiviral drug introof their accidental prescription together yet end up in the European Court of duced in September has been temporarily with sorivudine had been anticipated; Justice. Meanwhile, Social Affairs Commissuspended by its manufacturer because of patients who have chemotherapy are often the drug’s association with deaths, believed are sioner in an immune suppressed state and so Padraig Flynn was given a rough ride to be due to its interaction with anti-cancer at the Parliament’s October session when for sorivudine. potential candidates : he was reluctant to take up the said the action taken the agents. Sorivudine, (+ )-l-&bgr;-D-arabino- : by he Apart from has uracil of Health the with. the Council of Ministers in an furanosyl-5-[(E)-2-bromovinyl manufacturer, cudgels Ministry is effort more concessions. Only an antiviral to to wrest order to refrain issued an (Usevir, Nippon Shoji), drug physicians of for treatment zoster. with when the It to from the developed assembly threatened to reject the herpes giving drug patients can be given orally and the product has a entire proposal did he agree to support unknown medication profiles and to people Strasbourg’s amendments-having warhighly selective inhibitory action that is : with histories of cancer. times that of ned that the entire directive might be lost. 50 approximately acyclovir. Over 500 000 tablets have already been sold Makato Yawata : Spokesman for the Social Affairs Comto 10 000 medical institutions in Japan. mittee, Belgian MEP Mr Raphael Before being put on the market, sorivuChanterie pinpointed the key amendments dine had been known to induce severe among the many being sought by MEPsleucopenia when used in combination with Debate on doctors’ working that the directive should include a "nonthe pyrimidine metabolism antagonist regression" clause to prevent member hours states using the EC legislation as a pretext fluorouracil, and a warning had been to water down existing national standards; printed with the instructions for use. that it should incorporate a specific referDespite this precaution, adverse effects ence to ILO standards and set out a British demands that junior doctors should were reported in the month after the reference period over which night work be denied protection under EC legislation introduction. There have been at least 7 on could be calculated; and that it should of to this and serious effects due holiday reports working hours, night work, drug have been condemned in 3 of the have the died. interaction; pay patients European create "a basic level of protection for as Parliament. British Labour MEP there have been claims that the Stephen many workers as possible", not provide Although said: "We can wonder at the were insufinstructions Hughes only exemptions for numerous occupations. drug warning Another sticking point concerned barbarity of the UK government negotiatficiently strong, a possible contributory factor could be the lack of informed patient implementation: members states would ing a clause to exclude junior doctors from have three years to transpose the directive the terms of the directive". He said it was consent in Japan. Sometimes patients on into national legislation and would then antitumour drugs do not know that they "reprehensible in the extreme" that the have seven years as an "opting out period". British authorities should be prepared to have cancer. According to a nationwide
Deaths due to drug interaction
survey conducted last year by the Ministry of Health and Welfare, only 18% of cancer
1166
put doctors’ health and that of their patients at risk. Whether the legislation will
Arthur
Rogers