Report: Global API GMP Inspection Coordination Increasing Under Joint Program
Executive Summary
Regulators report that an international collaboration on GMP inspections of API sites has bolstered the exchange of information between participating health authorities, yet the information technology system that supports the system could use some improvement.
Regulators report that a program of jointly coordinated third-country inspections of active pharmaceutical ingredient manufacturing facilities has been successful in reducing the number of duplicative inspections at sites throughout the world.
The program began as a pilot project in 2008-2010, and was implemented on a permanent basis in January 2011. Regulatory authorities cobbled together a spreadsheet-based master list to coordinate inspections for the pilot. Seven years later, it appears that the cumbersome master list will be replaced by a sophisticated database.
The program already has increased inspectional efficiency among inspectorates in its first six years, says a report that the European Medicines Agency posted online April 12. Switching to a more powerful database is likely to further improve coordination, enabling regulatory authorities to further increase their scrutiny of API facilities even if they don't add inspectional resources.
The regulators noted that “based on analysis of the individual deliverables and key performance indicators … the migration from a pilot program into a permanently running scheme can be considered successful as most of the objectives were achieved.”
The program received positive reviews from FDA officials about two years after its launch. At that time, nearly 100 inspection reports had been shared and nine collaborative inspections performed. (Also see "US, EU and Australia reveal positive outcomes from pilot GCP and API inspection projects" - Pink Sheet, 4 Aug, 2011.)
These were the objectives of the program:
- Increased transparency and visibility of inspections performed by participating authorities;
- Overall increase in the number of API sites inspected by participating authorities;
- A decrease in the number of duplicate inspections;
- An increase in the number of inspections performed of value to more than one authority; and
- Assessment of the deliverables by the participating authorities
Regulators involved in the collaboration include EMA, several EU national authorities such as France, Denmark, Ireland, Italy and the UK, the European Directorate for the Quality of Medicines, the US FDA, Australia’s Therapeutic Goods Administration, Health Canada, the Japanese Ministry of Health, Labor and Welfare, Japan’s Pharmaceuticals and Medical Devices Agency and the World Health Organization.
The report noted that since the program launched, 1,333 inspections have been conducted at 458 manufacturing sites of common interest. These sites were spread among 18 countries, yet most were in India (49%) and China (36%).
Over the six-year study period, the authorities found they had inspected non-compliant sites at a higher rate, even after setting aside inspections some of them were required to conduct to confirm non-compliance. Sites with at least one non-compliance finding were inspected at a roughly 34% higher rate. It is possible, though not certain from the data, that authorities were redirecting resources away from inspecting sites with strong compliance records.
The report suggested that some duplicate inspections may have nevertheless resulted from possible failures to include all relevant information in the master list or to review the master list, of to act on data in the master list for internal, logistical, administrative or legal reasons.
Another finding was that authorities could and did recognize each other's inspection outcomes, and that they facilitated oversight by sharing inspection reports.
The report noted that over the six-year period studied, authorities conducted 47 joint inspections at 43 sites.
The US FDA conducted the most inspections, 762, followed by European authorities at 310 inspections and the World Health Organization at 131 inspections.
Switching From Spreadsheet to EU Database
The program has had its drawbacks. For example, the master list, which is a spreadsheet used to coordinate inspections, could be improved upon. The master list consists of sites of common interest and serves as a primary focus of communication between authorities.
The master list has been an ongoing problem going back to 2011. A May 2011 API inspection pilot report said that although the spreadsheet provided a great starting point for the pilot, the updating process “was not fully satisfactory.” The problem was the lag time involved with EMA waiting for participants to forward information, then compiling the updated information and distributing the updated spreadsheet to all the participants. (Also see "Mutual Reliance Blossoming Among FDA, EMA, Other Inspectorates" - Pink Sheet, 26 Jan, 2012.)
Since then the sheer volume of information added to the master list has made it more labor-intensive to update, the report said. It is especially challenging because only one party can have control of the document at a time. The parties don't have a common IT platform, and often must resort to emailing data to each other.
To improve the exchange of information and to facilitate the timely and accurate information on the sites, a proposal was made to use the EU's drug GMP inspection database instead of the master list.
It is expected that the full migration to the EudraGMDP database will continue throughout 2018, with the final steps depending on the resources of the participating authorities.
From the editors of the Gold Sheet.