Excipient certification scheme officially launched

A four-year effort to develop a certification scheme for excipients has come to fruition, giving drugmakers a means to ensure that substances used in their drugs are made and distributed to appropriate standards.

The scheme - called EXCiPACT - was officially unveiled to the world on January 25 at a busy meeting in Barcelona, Spain, attended by a comprehensive mix of stakeholders, including excipient suppliers, distributors, users and regulators.

The aim of the project is to make use of certifiable quality standards - focusing on good manufacturing and distribution practices (GMP and GDP) - which can be used to identify reliable suppliers and distributors of excipients.

With those standards now developed, marketing authorisation holders can use third-party auditors to assess suppliers and get a clear picture of whether they are meeting those criteria without having to carry out multiple and often duplicative audits.

Introducing the new initiative at its launch, EXCiPACT chair Folker Ruchatz said that recent events such as the contaminated heparin scandal, DEG-contaminated glycerol and melamine in milk products have shown that there is threat to supply chain security in pharma, affecting not only active substances but also excipients.

"Regulators expect market authorisation holders to secure their supply chain, and the best way in our opinion to achieve this is to substantially increase periodical, physical audits of manufacturing sites," he told the meeting.

However, this requirement poses "an economic burden on both manufacturers and users," according to Ruchatz, given the costs - both financially and in man-hours - involved with multiple customers carrying out audits on a supplier.

EXCiPACT overcomes this by allowing a supplier to be certified by an independent, third-party organisation - who would in turn be vetted by the EXCiPACT organisation - on a set of standards that have evolved from the widely-used ISO: 9001 and IPEC Europe GMP and GDP guides.

If successful the supplier can present the certificate to customers as evidence of its compliance with standards. The organisation will have to be recertified every three years under the scheme.

In parallel a new American National Standards Institute (ANSI) excipient GMP standard is being developed by the NSF - with input from Excipact and others - as ISO:9001 is less commonly used in the US. Having both in place will potentially allow dual certification across both markets.

Giving the perspective of a pharmaceutical manufacturer at the launch meeting, Janeen Skutnik-Wilkinson of Pfizer welcomed the launch of EXCiPACT, nothing that while it may not replace all audits by pharmaceutical companies it will have a significant impact.

Drugmakers could rely on EXCiPACT to cover the essentials such as GMP, freeing up resources to audit suppliers based on their specific use or needs, she added.

Speaking at the meeting via telephone link, Steven Wolfgang acting director of the FDA's recently-formed Office of Drug Security, Integrity and Recalls, noted that lengthening and more complex supply chains are posing hazards in terms of falsification of drug ingredients and deficient quality systems which can lead to the infiltration of substandard or adulterated materials.

"FDA is increasing its focus on pharmaceutical supply chains … and we are looking a lot closer at excipients these days than we were doing seven years ago when I joined the agency," he said.

There is recognition that government agencies are not as expert as the regulated industries in some areas, said Wolfgang, pointing out that at the end of last year the FDA published a report recommending that industry and other stakeholders should be encouraged to submit draft standards and guidance for consideration by the agency.

The launch of the EXCiPACT standard ties in with that trend very well and represents "a tremendous step forward in building the framework of global excipient quality assurance and supply chain security," he said.

Cost savings

Aside from the patient safety benefits in ensuring that all ingredients which go into medicines are manufactured and shipped in the most appropriate way, EXCiPACT will bring significant cost-savings, according to Frithjof Holtz of Merck Millipore, who has been closely involved with the development of the scheme.

Maintaining EXCiPACT certification for a plant will cost around €30,000 over a three-year period, but achieve net savings of €60,000 for the excipient supplier and €240,000 for the pharmaceutical company over the same period, based on a saving of just one two-day audit per month, said Holtz.

"The next steps are to test the standards and use them to assess excipient suppliers," said Iain Moore, EXCiPACT's project coordinator, who noted that pilot audits will be carried out starting in early 2012.