China is regularly cited as a major source of poor quality active pharmaceutical ingredients (API), partly because manufacturers in the country – which supply around 40 per cent of the world’s drug actives – have been linked to a number of high-profile scandals in recent years.
Lembit Rägo, World Health Organisation (WHO) coordinator for medicine quality and safety, acknowledged this but told in-Pharmatechnologist.com that the issue is more complex.
“There are Chinese manufacturers supplying APIs of high quality to multinational companies, but there are also companies producing APIs of poor or not defined quality."
Dr Rägo also called for pharmaceutical firms to play a greater role in the battle against poor quality APIs, pointing out that: “As long as there are customers for substandard APIs they will be produced and sold.
“We cannot advise [pharmaceutical firms] not to source APIs from China. This would likely have devastating results for availability of many lifesaving medicines for alternative sources may not be available. Our efforts are to advise about API standards and how implement and enforce these standards. This is relevant both for producing countries as well as countries, which purchase APIs from abroad, not talking specifically about China.”
Standard of substandard?
The root cause of the issue is the disjointed approach to policing according to Rägo who said: "The problem of substandard APIs is due to the lack of unified global standards for quality combined with total absence or weakness of regulatory enforcement in most of WHO 194 member States.
"We also have to think what is “substandard”? Substandard in one jurisdiction may not be necessarily substandard in another jurisdiction.”
In some countries API manufacturers are not required to comply with good manufacturing practices (GMP) he explained, going on to say that in others regulators either do not assess product quality or lack the capacity to inspect production sites.
“Thus an option that they authorize medicines with 'low quality' of APIs involved is very likely.”
However, while the picture may be bleak at the moment, “things are changing and regulators gradually pay more attention to API quality” Rägo continued, cited new European Union (EU) rules requiring local regulators to assure that manufacturers meet GMP standards if supplying actives for drugs sold in Europe as an example of the work being done.
The WHO also operates a prequalification scheme for APIs for medicines for HIV/AIDS, malaria, TB and reproductive health in collaboration with various regulatory agencies around the world, which Rägo believes is having appositive impact on quality.
“As many of these medicines are manufactured by small generic companies in many countries who have no capacity to assess the API sources combined with the weakness of national regulatory systems it is anticipated that making quality API sources available can help let us say manufacturers in Africa to source quality APIs for their local production.
The situation is also starting to change in China. Traditionally, the Chinese Food and Drug Administration (SFDA) has focused more of its limited regulatory resources on products for the country's internal market and has not paid much attention to the quality of exports.
However, the organisation’s recent adoption of ICH Q7 GMP is a move in the right direction according to Rägo, even if full implementation is likely to take time in a country the size of China.
“We are working, with the help of best expertise possible from our technical partners, with Chinese competent authorities and manufacturers. It is a long way to go but things have started to move.”
Rägo concluded by stressing the importance of efficient and effective collaboration between regulators worldwide.
“It is not feasible for all regulators duplicate efforts. However, it is feasible for all regulators to start to function as an effective and efficient network that tackles the problem combining the efforts and scarce resources.”