“The world has changed,” Guy Villax told a crowded room at CPhI, Paris today, as when he began working at Hovione in 1985 the firm was selling Portugese-made APIs to India. Almost 30 years on, the now CEO said the majority of APIs are now being made in India and China, and warned that regulators are not organised to control the international industry.
With perhaps Eli Lilly in Ireland the exception, he said there have not been any API plants built in Europe for a long time. The shift of API manufacturing to Asia has also caused R&D to be localised, he continued, but despite upped demands from regulators a number of high profile warning letters and import alerts (issued to Ranbaxy, Canton Labs etc) means the industry is now under pressure to reform.
“Unless there is a change in the driving forces the quality of medicines will decline globally,” Villax warned, adding that despite approximately 80% of APIs in Europe coming from India and China, there is still only a 2% chance that a foreign inspector has visited a plant.
The European Commission has demanded written confirmations from API suppliers, while in the US the FDASIA and GDUFA guidelines have been introduced to help ensure safety and upping the number of foreign inspections.
Furthermore, API audits are now mandatory every three years but in order to ensure quality in the supply chain “the sharing of audit reports [among clients] is essential,” Villax said. “Unless we do that quality problems, [quality assurance from APIs] is not going to work.”
Heparin Example
GMP exists for ingredients because it is impossible to analyse the product at the end of the production, he said, and as the first part – and most important element – of the finished dosage it is essential to ensure your API supply has been audited.
If not, the drug industry will be liable to be subject to scandals such as the heparin contamination which killed at least 81 in the US after falsified API, imported from China and falsely labelled, entered the supply chain.
“Though the focus of fake drugs is on those you see in your email spam – Viagra, Epogen etc – fake APIs and excipients are the real problem,” Villax said. The appeal to make fake or sub-standard API is huge, he said – in 2006 heparin API was selling for $6,000 per kg – and such perpetrators are rarely caught.
Furthermore, the presence of cheaper, lower quality (or falsified) ingredients makes it hard for honest and good quality API makers to compete, and therefore pharma’s own procurement teams must take some of the blame in the drop of quality, along with the low-cost supplier.
“If you are a purchasing manager, you know it is a complicated supply chain and therefore if the price of an API suddenly triples – [as it did with heparin in 2006] – you should know something is amiss. This is not just a QA issue.”