GMP News No. 172
27 February 2002
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What now, MRA?
In December 2001 the three-year transition period of the MRA agreement between the EC and the USA expired. The purpose of this transition period was to allow time to confirm the equivalence of the inspection systems in order to be able to do dispense with the need for reciprocal inspections. Whereas the EC evaluation of the American system is nearing completion, the FDA has only evaluated one EC member state, the United Kingdom, to date.
This means that the transition phase will have to be extended.
According to EMEA, the European regulatory authority, a plan is still needed as to how to proceed further in order to be able to consider an extension. Particularly since the EC demands a pledge from FDA that the evaluation of all the EC states will really be completed during the extended transition period. FDA is still hesitant in this regard since, according to Joseph C. Famulare of the Office of Compliance, CDER, MRA is only being processed as the internally available resources allow.
In the year 2000 the USA already published the sequence in which the other EC states were to be evaluated:
According to Famulare, the main reasons why the process is dragging so much are translation problems and lack of resources. Famulare said that the paper review of the EC states would be delayed by months since most of the countries had submitted their documents in their national languages. The USA then returned the documents to the EC commission asking for them to be translated since they were not in a position to have the documents translated themselves. The EC Commission then assured the USA that at least certain documents would be translated. Famulare said that joint audits to confirm the inspection practice could not begin before the paper review had been completed.
The FDA's suggestion of a "rolling implementation" of individual EC states by the USA was greeted by the Europeans with reserve since it contradicted the concept of a united Europe.
FDA responded to this with an interesting suggestion for speeding up the procedure, an "interim step". The idea is for the participating states to exchange inspection reports already during the transition phase. With the help of these inspection reports FDA could decide not to send any inspectors to the individual countries for joint audits. This seems to be acceptable for the Europeans, too.
The expansion of the EU to include eastern European countries might cause additional problems. How does FDA want to deal with the new members?
The rapid alarm system which is already in operation is to be expanded. Unfortunately there are problems here, too. FDA wanted an expansion of the already existing SOPs to permit an exchange of field alert reports. The Europeans, however, would rather complete the transition period first. It was extremely difficult to coordinate the currently valid SOPs within the EC.
What is more, at present the confirmation by the EC concerning the handling of confidential commercial information is still pending.
A new aspect concerning the MRA agreement are the critical remarks of the US industry. They fear that the absence of FDA inspections in Europe upon completion of the transition period will lead to injustices in the follow-up measures to inspections. There is also even the fear in some quarters that fewer pharmaceutical companies will be set up in the USA.
The former head of the Office of Compliance, Stephanie Gray, has also warned of inequalities in the strictness of inspections in and outside of the USA.
The MRA agreement between the EC and Canada , which also became effective at the end of 1998, but which provided for a transition period of only 18 months, has been all but forgotten. The operational phase should actually have started long ago, but here too commencement has been postponed to the end of 2002.
An MRA agreement between the EC and Switzerland is scheduled for ratification in mid-2002.
Gold Sheet, October 2001
We must therefore continue to expect FDA audits in cases where we export to the USA. In order to prepare you for FDA's special requirements, we offer you the following Education Courses: