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API quality enforcement in disarray; Villax

By Nick Taylor, 17-Nov-2009

Related topics: Excipients, raw materials and intermediates, QA/QC, Regulatory & Safety, Globalisation, Counterfeiting

Regulatory enforcement efforts to tackle counterfeit and substandard APIs are in disarray, according to Guy Villax, CEO of Hovione, who spoke at AAPS about the scale of the problem.

Criminals have seized on counterfeit pharmaceuticals as a low-risk, high-profit alternative to illegal narcotics and, although the industry has taken some measures, this has led to them spreading.

Enforcement is in disarray”, claimed Villax who added that although regulatory agencies have done a “terrific job” keeping up with scientific developments they have failed to pay enough attention to the industry.

This has resulted in regulatory bodies’ outlooks being largely national in an era of rapid globalisation, when an “endless chain of middlemen” muddy the active pharmaceutical ingredient (API) supply chain.

Failure to adequately monitor and police this supply chain could have severe consequences. Villax explained that a single batch of API could be used in drugs for up to 100,000 patients to show the harm substandard raw ingredients could cause if they enter the legitimate supply chain.

Stopping substandard APIs being used in legitimate drugs is a significant challenge though. Successful Chinese API manufacturers deal with over demand by purchasing additional supplies from other companies and relabeling the product, according to Villax.

These ‘shadow factories’ further complicate the supply chain. In addition Villax believes that some API manufacturers close off areas of their facilities when auditors visit and consequently the onus is on inspectors, with their greater authority, to check all sections of a site.

The consequences

By continuing current practices another contamination like the heparin case could occur. This is a case where a “hugely complicated supply chain”, with 1,000 workshops producing 20 tonnes of heparin, contributed to contaminated products reaching patients.

Another significant contributing factor is greed. Villax explained that a rise in the cost of pig feed and an illness that killed pigs placed economic pressures on heparin manufacturers; some responded by adulterating the product with oversulfated chondroitin sulfate.

When “there are a small number of people that have non-compliance as a business strategy” effective regulation and enforcement is needed to decrease the likelihood of another contamination incident.

Taking action

Villax believes that regulatory agencies are “still very far away from making optimal use” of the limited resources available and added some suggestions as to how the situation could be improved.

He added that regulators need to establish rules, know all the players in the market and improve detection and punishment, which he believes is “very weak” in most countries.

Part of the problem is the lack of legislation dealing specifically with counterfeit medicines in many countries. In these nations counterfeit pharmaceuticals are classed as a patent infringement but, given the potential harm, Villax believes this is insufficient.

Most countries are “desperately short” of the sort of sanctions needed, according to Villax who advocates “strong deterrents” and a “name and shame” policy.

However, this must be supported by knowledge of who manufactures APIs. Villax explained that the European Union has struggled to make a list of API producers, adding that the FDA’s database “makes no sense” as some companies submit a drug-master file (DMF) just to improve their reputation.