Implementation of Europe’s Falsified Medicines Directive (FMD) has shed important light on what the active pharmaceutical ingredient (API) part of the global pharmaceutical supply chain actually looks like and has led to enhanced communication between the countries that participate in it.
One of the four basic components of the FMD involves increased assurance that all APIs being imported into Europe have been manufactured under EU-level GMPs. The directive also strengthens the EU requirements for: ● product identification and tracking ● good distribution practice, and ● Internet pharmacies.
Coming into force on July 2 was the directive’s requirement that API manufacturers must get written confirmation from their domestic regulatory authority that they are in compliance with EU GMPs before the EU will grant entry of their product, if their country has not been formally recognized as having an equivalent GMP oversight system (IPQ “The News in Depth” May 31, 2011).
In addition to the written regulator confirmation, manufacturing authorization holders (MAH) in the EU must assure themselves, through audits, that the active substances they are using have been manufactured and distributed in accordance with GMP and GDP. Presence of the written confirmations and the audit programs will be checked during routine MAH inspections.
A third possibility, intended for use when medically necessary products are involved and the previous two pathways are not available, is for an API plant to undergo an inspection by an EU authority and be issued a GMP certificate that allows importation.
The FMD API import provision has led the EMA, in conjunction with the member states, to carefully map out where all of its APIs are coming from and has intensified the dialogue between EU regulators and authorities in countries with firms that manufacture APIs intended to be exported into Europe.
At a conference on the “Current and Emerging EU Regulations and Inspection Trends” co-sponsored by PDA and the Irish Medicines Board (IMB) in Dublin, Ireland, in July, EMA Senior Scientific Administrator Riccardo Luigetti highlighted the impact that the FMD implementation process is having on inter-agency communications and cooperation.
The FMD “has increased dialogue and cooperation between the EU and key third countries from a commercial point of view,” he commented. “The European Commission, the member states, and EMA are talking much more with the third country authorities.”
Implementation of the FMD, Luigetti emphasized, “is also facilitating the process for third countries to become part of the global regulatory system. The EU has led this process. The aim is to bring them to our level in the future.”
[Editor’s Note: An update on the FMD was provided by EMA on its July 2 implementation date. The update covers: ● what is required for written confirmations to guarantee GMP standards ● the list of countries that have applied for equivalence determination and the status of the applications ● an explanation of the waiver for APIs being imported that cross-references a separate guidance and decision tree published by the EU in June, and ● a description of the goals of the FMD as a whole. The update is included below.]
Supply Chain Vulnerabilities Mapped
At a conference on “Redefining the ‘C’ in CGMP” cosponsored by ISPE and FDA in June in Baltimore, Maryland, UK Medicines and Healthcare Regulatory Authority (MHRA) Inspections, Enforcement and Standards Division Director Gerald Heddell discussed the API supply chain “mapping exercise” that MHRA and EMA conducted and how the results are being used to understand the locations of the suppliers and the vulnerability of the supply chain for active substances being imported.
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Analyses of Defect Reports by Ireland’s IMB and FDA Highlight Packaging and Labeling as Key Pharma Manufacturing Problem Area