Van Dalen raised her concerns at a drug industry event in Barcelona, Spain this week, suggesting that regulations (2011/62/EU) introduced in 2011 to encourage non-EU countries to seek EC assessment of national manufacturing standards to aid local producers have not worked as expected.
“Every country outside the EU can request to be added to a list of so-called third countries…if you are on that list it means that the European Commission has evaluated that the GMP system and the controls in your country are equivalent to those in Europe – ICH Q7.”
Written statement
A few non EU countries are on the list – Australia, Japan, the US, Israel, Brazil – and others like Singapore, New Zealand and South Korea have applied.
However, the fact most countries have not sought third country status is evidence of weaknesses in the system according to Van Dalen. She suggested the workarounds introduced to prevent the regulations creating drug shortages are the problem.
“There is a way out. If your country is not on the list you can have a “written statement” signed by the authorities in the country of origin that needs to accompany each batch of API that is coming into European markets.”
APIC sees a number of problems with the approach according to Van Dalen, suggesting that the written statement system creates an imbalance.
“It’s a bit hard to believe that you [a country] cannot meet GMP requirements if researched by the Commission, but can write on a stamp that it is sure people in the country are producing under GMP...That seems to be quite imbalanced and unbelievable.”
Differing implementation
Van Dalen also pointed to differences in how the written statement regulations are implemented in EU countries as a major issue, suggesting they leave room for confusion and complicate tracking in Europe.
“This is European law, but if I go to the Dutch authorities and ask if API imports are being checked at customers they will say no, we inspect the drug product manufacturer and check with the qualified person if he has reviewed this written statement before signing the QP declaration.”
“But If I ask in Germany, customs will have a list of written confirmation as they have to check [API imports] at the border before it comes into the country.”
GMP options
Under the regulations, non-third country API producers wishing to sell to EU customers can also ask European authorities to inspect their manufacturing operations.
However, “EU authorities very often do not inspect API facilities in their own countries” according to Van Dalen, who suggested any authority that does agree to assess manufacturers overseas first would likely face criticism from local producers.
“European industry says, if you want to go out on inspections, please start in our own countries, because a GMP certificate is quite important to the API industry…it means access to a lot of markets outside the EU.”