Global Rx-360 Consortium Aims To Curb Supply Chain Threats

Drug manufacturers formed the Rx-360 consortium as a vanguard in protecting the global supply chain of ingredients for Rx and nonprescription drug products from threats like the heparin adulteration potentially linked to 146 U.S. deaths in 2008.

Consortium members hope to chart an approach that can become standard industry practice in time to prevent similar incidents. Also, the group hopes to establish this global approach in time to serve as a framework for emerging regional standards and regulatory requirements.

"The mission is simple," Amgen Quality VP Martin VanTrieste told the International Forum for Process Analytical Technology meeting in Baltimore on Jan. 26. "Improve the quality, authenticity and security of the supply chain so that patients benefit. Patient safety should never be a competitive advantage."

The consortium grew out of discussions among participants in a series of supply chain conferences that the Parenteral Drug Association and FDA launched after heparin contamination problems in 2008 showed that drug supply chains for industrialized nations could be compromised by the introduction of deadly adulterants (¹ (Also see "FDA Strengthens Inspections Of Chinese Drug Firms In Heparin Aftermath" - Pink Sheet, 10 Nov, 2008.), p. 13).

"A group of individuals said this problem has to be attacked in a very holistic manner from a global perspective and no one organization can do this by themselves - no one company, no one regulator - because it is of such a global nature," VanTrieste said in an interview.

VanTrieste, who is a key participant in the initiative, said the consortium will hold its first meeting June 5 in Washington following the ISPE's conference June 1-4, which will address supply chain security among other issues.

The meeting will bring together interested parties including suppliers, regulators and pharmaceutical and biotech companies, both brand and generic.

The group drafted a proposed plan and posted information online at www.rx-360.org. Executives with more than two dozen drug product manufacturers and other organizations so far have said they want to participate.

Initial outreach was to pharmaceutical and biotech manufacturers, but was extended to suppliers, brokers, distributors, repackagers and relabelers.

The consortium's supporters so far include an array of Rx and OTC drug product manufacturers: Abbott, Amgen, Amylin, AstraZeneca, Baxter, Bayer, BiogenIdec, Bristol-Myers Squibb, Cephalon, Covidien, Genentech, GlaxoSmithKline, Johnson & Johnson, Lilly, Pfizer, Roche and Schering-Plough.

Officials with two key regulatory agencies, FDA and the European Medicines Agency, favorably reviewed the consortium's concept.

FDA plans to hold a public workshop this spring to gain advice from industry and the public on keeping fake or adulterated ingredients out of the supply chain (² (Also see "FDA Seeks Public Input On Secrets Of Profit-Motivated Adulteration" - Pink Sheet, 2 Mar, 2009.), p. 5).

The agency also is launching a voluntary pilot program aimed at helping prevent contaminated drugs from entering the U.S.

Holistic Approach With A Bias For Action

VanTrieste said the consortium brings a holistic perspective and a bias for action greatly needed because moving quickly is more important than perfecting the approach before acting.

"We want to say that perfection is the enemy of good," he said at the IFPAC meeting. "We could make the perfect document, but look how long it takes something" to process through the International Conference on Harmonization or the International Organization for Standardization.

"We can't do that in the consortium. We need to prevent that next heparin event as quickly as possible."

The organization aims to build mainly on the activities of others. For example, it can adopt supply chain controls others separately developed for excipients and active ingredients. Then it can work out how to coordinate those controls for ingredients that are excipients for some drug products and active ingredients for others.

Plus it can add comparable controls for other types of critical materials such as raw materials, chemicals, filters, containers, stoppers, labels and cartons that also need standards even though they are not active ingredients or excipients.

This way, biopharmaceutical manufacturers could have one solution to adulteration threats for all materials they use. Eventually, the consortium's template could feed into an international standards process such as those of ICH or ISO.

Working With A Three-Year Plan

The Rx-360 consortium established a three-year plan to advance its goal of securing the global pharma supply chain and ensuring the quality and authenticity of the products moving through it.

The plan focuses on establishing four functions: standard-setting, technology development, data sharing and the sharing of audit information.

"The first year is to get the standards and the infrastructure. The second year is to really get the shared auditing piece up and running, and the third year is to be working with big research institutions and universities" to develop technologies for detecting adulterations, VanTrieste said.

Although Rx-360 intends, where possible, to review and adopt standards others have developed, VanTrieste said it would develop standards itself where necessary to fill gaps.

For example, he said, "nobody right now is doing a lot in good importer practices" beyond a draft guidance FDA issued in January. "Do we need to do something along those lines? Let's look for gaps in the system and try to address those gaps."

Additionally, the consortium aims to work toward a common audit method. "We need to agree to what that process is, so when we do a GMP audit of a supplier or a good distribution practice audit of the supply chain, we need to be doing it the same way. If it's a company auditor, if it's a third-party auditor from one company or another, we need to all be doing the audits in the same way. ... That's a big part of what the consortium can do - drive that consistency of approach," VanTrieste said.

Consortium members will share audits, which should enable suppliers to host fewer but more effective audits. However, participation in the audit program will not be required. Companies can belong even if they are unwilling to share their audits with the other members.

The consortium also is taking a flexible approach for types of audits it will accept. Firms can submit information from their internal auditors to the consortium, or hire third-party firms certified to the consortium's standards and provide those audits to the database.

Technology development may involve collaborations with the Massachusetts Institute of Technology's Forum for Supply Chain Innovation, which has a radio frequency identification laboratory, and a partnership with IBM for developing electronic pedigrees.

Another possibility is the National Institute for Pharmaceutical Technology and Education, a research group formed by 11 pharmacy and pharmaceutical engineering schools that expressed support for the consortium.

Spotting Supply Chain Vulnerabilities

The consortium intends to play a key role in sharing information about possible threats to the pharmaceutical supply chain's integrity.

For example, VanTrieste said it already is sharing concerns about a worldwide shortage of acetonitrile.

The solvent, commonly used in fluid chromatography, is a byproduct of acrylonitrile, an industrial chemical used in manufacturing synthetic polymers such as acrylic fibers.

A shortage of acetonitrile resulted largely from a sharp drop in acrylonitrile production as demand has dropped during the economic slump. Some labs are paying a premium, but others are looking to switch solvents. Experience suggests such an environment could be ripe for introduction of counterfeit solvent.

"People are thinking about what is the impact to our processes, our testing labs because of this shortage," VanTrieste said. "How could someone adulterate this product and take advantage of this shortage to make an economic profit by adulteration? Is there a detection mechanism we can put in place to assure that when we buy acetonitrile for these critical applications we can test to make sure it wasn't adulterated? So we have people working on that already."

- Bowman Cox ([email protected])