Counterfeit, Rogue  or Contaminated; No Matter What You Call It, It’s About Putting Patient Safety First

by Chris Oldenhof, DSM
President of APIC
Board member of EFCG

The date is 16 April 1998. Five regulatory affairs experts from five different European API manufacturing companies gather in a meeting room in Delft, The Netherlands. They have called themselves “The APIC Counterfeit Task Force” and have no idea yet that this meeting will be the very first step on an extremely long journey during which a lot will be learned….

The reason for CEFIC’s European API manufacturing industry’s sector group APIC to establish this Task Force was the increasing number of “stories” that members of the association were exchanging amongst each other. And the stories all came down to the same thing:

“We have in a number of cases gone through very tough, intensive trajectories with health authorities for certain prospects / customers with our DMF and CEP applications in order for them to get authority approval for their drug products. But after approval had been achieved it appears that our actual API sales to certain customers remain very limited or even zero. Could API material possibly be coming in from elsewhere and is this material covered by any regulatory submissions at all?”

At that time in Europe, contrary to the situation in the USA, the legal requirement for API manufacture to comply with GMP was still lacking and was only to be implemented seven years later. So we could only base our suspicions of “API counterfeiting” on the fact that the approved drug registrations possibly did not include the API material from those supposed other sources. The transparency of the authority databases was insufficient to enable us to prove our point…
 
To many non-experts the entire issue was making the impression of not being “a really big deal” but to us, the registration experts who were fully aware of the involved health risks to patients, using a non-registered API was nothing less than an unscrupulous crime with serious health implications.

Moreover, our suspicions also included APIs destined for the US market where GMP compliance for APIs was already required by law for decades. So using non-registered, non-GMP compliant APIs would be a double crime!

In that meeting room in Delft we started making our first plan of action. It was a quite simple one that consisted of 1) drafting a presentation to explain the issue and 2) compiling a list of institutions where we would want to give the presentation:

• The Dutch, French, Spanish and Swiss health authorities (the respective countries of origin of the five task force members)
• The Pharmaceutical Unit of the European Commission’s “Directorate General III”
• EDQM
• EMEA
• US/FDA

At a later moment in time we added:

• BfArM / Germany
• The Permanent Forum on International Pharmaceutical Crime
• The Pharmaceutical Security Institute

It was a typical case of “Let’s just get started and see what will happen next”.

For many years APIC has worked hard to obtain attention for this serious issue and for related ones from many different stakeholders: Health authorities, other pharma industry sectors, politicians, media, patient organizations, traders... But for quite some time it was very hard to get any support and in fact we felt that some stakeholders rather tended towards opposing than towards supporting us.

As from 2004 onwards another, newly founded CEFIC sector group, the EFCG (European Fine Chemicals Group), representing upper management of European fine chemicals manufacturers, joined sides with APIC and soon became the front runners for this issue.

As time progressed serious health incidents with pharma (and non-pharma) ingredients increasingly underlined the points we were making. The dramatic consequences of deliberately contaminated heparin formed the ultimate eye-opener, though as opposed to the USA, Europe seemed to have crawled through the eye of the needle.

It is not difficult to imagine with an API such as heparin, administered annually to millions of patients, that if the contaminant would have been more toxic than it actually was, then the number of casualties, also in Europe, would have run into the many thousands or more.

Eleven years have now elapsed since those first five pioneers sat together in that meeting room in Delft. The contrast between the situation then and that of 2009 is in many respects enormous.

But what is maybe most important: We have learned to understand the issue.
Counterfeit Medicines, Falsified Medicines, Rogue APIs, Façade Constructions, Unsafe Supply Chain, Contaminated APIs, these are all inadequate terms to fully describe and clarify the problem. Still today one can hear statements, for example, such as “not one single case of counterfeited generic medicines has yet occurred in the EU”. But of course heparin is a generic medicine, so there are serious problems in relation to generics.

The problem cannot so easily be described by one term. What it is about is tampering - deliberate tampering for financial reasons - with the quality and safety of our medicines while disregarding the ultimate impact on the health and safety of very vulnerable individuals: patients. Irrespective of the type of tampering used, of who in the supply chain are tampering and of the name we give to each type of these practices, they all have one thing in common: They are unacceptable.

In brief: We should always put patient safety central in our thinking. Thus we can easily conclude that zero tolerance is the only option regarding deliberate tampering with the quality and safety of pharmaceutical ingredients for financial gains. It is high time to stop wasting efforts on discussing whether something is a “counterfeit” or not.   

One year ago my wife came home with a bag full of not-so-bad-looking umbrellas.
“Only one Euro a piece” she told me with a smile.
So if anyone of the readers during the past year has seen a person walking across Amsterdam Schiphol Airport’s Long Term Parking during stormy, rainy weather, holding a suitcase in one hand and a broken umbrella in the other and thus getting all wet, then it was most likely me.
The umbrellas looked like fairly good umbrellas but they definitely turned out to be unfit for use, especially when the weather is a bit windy. And in The Netherlands it is often windy.

If corners are being cut in the manufacture of umbrellas then the damage will usually be not much more than a wet suit for the owner. But if corners are being cut in the manufacture of APIs the price to be paid can be immense. Each batch of API corresponds to tens of thousands or even hundreds of thousands of patients. A fatal flaw in its quality may result in a health catastrophe of an unprecedented magnitude.

I would like to congratulate the founders of Rx-360 with their extremely important initiative and I am confident that the objective of a safe API supply chain has now become an attainable goal.