INITIATIVES: QUALITY ASSURANCE FOR ACTIVE PHARMACEUTICAL INGREDIENTS
The manufacture and transportation of APIs has been conducted within a highly globalised environment for a while. The expansion and harmonisation of networked official monitoring strategies as a necessary response to the potential dangers posed by qualitatively inferior or even counterfeit substances has been unable to keep pace with the tempo at which the globalisation of the market for APIs has taken place. Nonetheless, events such as the heparin scandal in particular have highlighted the need to ensure urgent action is taken at an international level. As a consequence of this necessity to avoid the infiltration of import streams by inferior or counterfeit goods, a pilot programme was initiated in November 2008 to conduct joint inspections of API manufacturers. Programme participants included the monitoring authorities of a number of European countries (France, Germany, Ireland, Italy and the UK), plus the Australian TGA and the US FDA. At the 13th Annual Conference of the European API manufacturers association APIC, held from 27-29 October 2010 in Barcelona, Olivier Gross from the European Medicines Agency (EMA) introduced this pilot programme and its achievements to date. Between 2009 and 2010, some 1,046 premises were inspected, including no less than 234 in China, 203 in India and 140 in Japan.
Another large-scale initiative designed to consolidate audit activities for API suppliers goes by the name of Rx-360 and was established by an international consortium of pharmaceutical manufacturers. The mission of this initiative is founded on the aim of developing a global quality system that can assure product quality across the entire supply chain. At the 13th APIC conference, Lynne Byers, designated Chair of the Rx-360 consortium, explained how this mission will become reality. Within the scope of a largescale pilot audit programme, a total of 10 audits at API manufacturers and 10 audits at manufacturers of excipients and basic chemicals will be performed at sites in the USA, the EU, China, India, Japan and other Asian countries. The audit reports will then be distributed among Rx-360 members. The project is being financed by member contributions.
Attempted fraud during an audit is just one of the many challenges that the auditors will need to overcome. A key factor that determines the success of an audit is being able to establish whether the audited organisation knowingly concealed or faked the results. Jean-Denis Mallet (SNS Lavalin) asked auditors to consider the risk scenario that is generated by errors that are concealed, undetected yet visible and obvious yet not fully investigated. Within a business, such errors stem from the pressures of process scheduling or streamlining, plus conditions that promote the incidence of error through the inadequacy of QA systems. Above all, auditors must take the various cultural aspects into account during their audits; this applies in particular for Far Eastern and African nations, and in countries with high levels of corruption.
Recommendation
5/6 February 2025
Handling of Foreign Particles in APIs and Excipients - Live Online Training
Stemming the rising tide of counterfeit active pharmaceutical ingredients is also the declared goal of EDQM. Based in Strasbourg and a directorate of the European Council, this authority has started an initiative for the discovery and proof of API counterfeiting. Francois-Xavier Léry of EDQM introduced the initiative. A major role is played by "API fingerprinting": the term refers to specific analytical methods developed by manufacturers of active substances to prove the presence of their substances. Together with the associated substance samples, these methods are submitted to EDQM, which forwards them to the Official Medicines Control Laboratories (OMCLs). Via this network, a database of substance-specific "fingerprints" is created, which simplifies the tracking down of fake medicines in proportion to the growing size of the database. EDQM is appealing for participation in this programme - which also provides strong legal safeguards for ensuring the confidentiality of sensitive data.
A different initiative - yet with the same goal of ensuring impeccable quality for pharmaceutical products - is being pursued by the WHO, with its pre-qualification programme for APIs. This pilot programme, which the WHO launched in October 2010, extends the already-existing pre-qualification programme for finished pharmaceutical products. The earlier programme already evaluated the API Master File and could involve GMP inspection of the API site of manufacture (this latter only in cases where a risk assessment recommended such action). The new pilot programme also includes evaluation of the API Master File but makes on-site GMP inspection mandatory.
However, this pilot programme does not cover all APIs. It is limited exclusively to APIs used to manufacture medicines to treat the four most important and widespread infectious diseases - namely HIV/AIDS, malaria, tuberculosis, influenza - plus APIs used in pharmaceutical products for birth control.
The responsibility for product quality does not end outside the manufacturer's factory gates. In recent years, there has been growing acceptance of the insight that the monitoring and unbroken surveillance of the supply chain is of decisive significance. This follows the increased incidence of cases of criminally-motivated manipulations to containers and the labelling of secondary packaging. Eileen Counihan (Merck, Sharp & Dohme) presented a number of simple yet effective strategies for monitoring and tracking containers as they proceed along the supply chain. This involves not only the performance of dealer and distributor audits conducted from a risk-oriented perspective: equally important is the meticulous surveillance and documentation of changes to closure systems and labelling.
Recommendation
Thursday, 13 February 2025 10.30 - 15.45 h
How to register APIs in Brazil - Live Online Training
The 13th APIC Conference once again made it clear that the global network created by the manufacture and supply of active pharmaceutical ingredients presents a challenge that must be taken seriously. The various initiatives currently being promoted by both regional authorities and industry organisations give grounds for hope that the threat to patient safety posed by inferior or counterfeit pharmaceuticals and pharmaceutical components can be countered in an effective manner. Meetings such as this once-yearly API conference offer an appropriate forum for the necessary exchange of information between the industry and the authorities and - last but not least - make an important contribution to the focusing of their activities.
Author:
Dr Gerhard Becker
CONCEPT HEIDELBERG
