The final results of the US FDA, EMA, TGA joint manufacturing facility inspection programme will make for interesting reading for API producers as they strongly hint the approach is here to stay.
The pilot programme , which began in December 2008 and ran for two years, was designed to reduce the number of duplicate facility inspections by fostering greater collaboration between regulators, enabling them to make better use of their respective resources.
According to the report during the collaboration regulators exchanged inspection reports for more than one thousand active pharmaceutical ingredient (API) production facilities worldwide which, after duplicate submissions were removed, was compiled into a ‘master list’ of 642.
Of these the European Medicines Agency (EMA), which was responsible for maintaining the list, identified some 238 completed inspection reports that were of interest to two or three participants.
The ‘master list’ was also used to plan joint inspection visits to API plants deemed of particular importance, nine of which took place between 2008 and 2010.
Duplicate inspections and logistical complexity
Despite these efforts some duplicate inspections still occurred. However, according to the EMA, this was mainly in 2009 at the beginning of the programme or because the inspecting authority deemed that the scope of the previous inspection did not match the pending approval request.
Of more concern is the EMA’s suggestion that some duplicate visits took place because the ‘master list’ was not examined by the regulator involved.
The report also details some unexpected issues that arose during the project, mostly related to communication difficulties between the regulatory agencies, the lack of common nomenclature and the need for greater use of available data during inspection planning.
Success :Nevertheless despite these issues the organisations involved deemed the scheme a success.
In a press statement the EMA said : “It was difficult to accurately assess an overall increase in the number of sites inspected…however, because of the sharing of inspectional information and of inspection reports, it was certainly possible that resources that would previously have been used for certain inspections could have been allocated to other priorities for example to inspection of sites which were not shared with other participants and/or which were never previously inspected.”
This was echoed by the US Food and Drug Administration (FDA) which said it “used these reports to inform decisions, such as whether to postpone or expedite its own inspection. The FDA also prohibited imports into the US of a firm’s products based on the negative findings from a European inspection.”
Continuation :The regulators also indicated that collaborative approach is likely to continue and could be extended to other industry watchdogs outside the US, Europe and Australia, provided that they have appropriate inspection infrastructure and comply with ICH Q7.
The EMA said: “Extending the programme to more comparable regulatory authorities and possibly the World Health Organisation would certainly need to be considered as a long term goal, as an efficient worldwide programme of inspections of APIs would be a notable benefit for public health globally.”
Industry response :The report was warmly received by the European Fine Chemicals Group (EFCG). Spokeswoman Annick Bonneure said that they had supported the project since its inception and welcomed the final results.
"We think that by far the most substantial result has been the exchange between the parties of each other’s inspection findings and other information. This is crucial for preventing duplication of efforts and on the other hand it enables each party to control the risks in the supply chain by acting on information generated by the other parties on severely non-compliant or even fraudulent producers and suppliers.
"The example of an FDA import alert that was issued solely based on inspection findings by EDQM is an example of which we hope it will set the trend for the future. She went on to say that it will be important that any legal obstacles that may limit the degree to which information can be exchanged and used will be tackled and broken down as soon as possible. "EFCG and APIC very much welcomed the news that the pilot project has in the meantime been transformed into an official cooperation project and that additional competent authorities are expected to join the program.
“Together with other legislative developments worldwide this cooperation project will not only gradually level the playing field in the API market but, much more importantly, it will ensure that, with regards to API supply chains, patient safety will be secured.”