Rx-360 Completes Pilot Audit of Manufacturing Facility: An Industry Case Study from Avantor

This article is part of a special issue on Outsourcing Resources

As pharmaceutical supply chains and distribution channels become more complex and global, there are renewed calls from public-health experts and Congress to ensure patient safety by demonstrating that supply chains are secure. A series of recent supply-chain breaches have demonstrated that a compromised supply chain is susceptible to counterfeit, diversion, dilution, tampering, and deliberate contamination—ultimately affecting thousands of patients every day.

In 2009, five bio/pharmaceutical manufacturers, distributors, and suppliers collaborated to form Rx–360, an international supply-chain consortium aimed at enhancing patient safety across the pharmaceutical supply chain. The voluntary group's mission is "to create and monitor a global quality system that meets the expectations of industry and regulators, and that assures patient safety by enhancing product quality and authenticity throughout the supply chain" (1). Today, Rx–360 has 64 members and continues to grow.

As part of fulfilling its mission, Rx-360 has begun conducting joint audits of its supplier members with the intention of sharing them with industry. These audits, designed to help establish and share best practices for supply-chain security, are designed to be more thorough than those conducted by individual pharmaceutical manufacturers because they focus on the entire supply chain from the origin of raw materials to shipment of product. Standards for the Rx–360 pilot audit, adopted by the Audit Standard Working Group, are based on the draft Excipact Excipient standard, the International Pharmaceutical Excipients Council/Pharmaceutical Quality Group (IPEC/PQG) Good Manufacturing Practices Audit Guide for Pharmaceutical Excipients, and the Rx–360 Basic Chemicals & Raw Materials Audit Guide (2, 3).

The audits carried out by Rx–360 are shared with the consortium's pharmaceutical manufacturer members, which regularly conduct their own independent audits of suppliers. The sharing of audit reports among industry is meant to reduce the number of repetitive audits hosted at a particular facility, allowing both pharmaceutical companies and suppliers to redirect resources toward higher risk suppliers and supply chains.

Rx-360 recently completed its first audit of a supplier member, Avantor Performance Materials, as part of a pilot program. This article describes Avantor's experience with the audit.

Background

Avantor Performance Materials, formerly Mallinckrodt Baker, joined Rx–360 in 2009. Avantor is a global supplier of critical performance chemistries and materials, including bulk pharmaceutical excipients, GMP-manufactured aqueous solutions, and process chromatography media.

Based in Phillipsburg, NJ, and with sites around the world, Avantor has a strong focus on supply-chain security. For example, the company operates a Certified Excipient Distributor program that is designed to assure customers that a certified Avantor channel partner uses fully documented chain of custody and change-management procedures. In collaboration with its suppliers, Avantor is also working to regularly review supply-management procedures; provide enhanced tamper-evident features on products; improve transportation-security measures; and to use advanced track-and-trace technology.

Several companies volunteered to participate in Rx–360's pilot audit program. The consortium conducted an internal survey of its manufacturers to determine which companies were suitable for participation. The goal was to choose suppliers whose audit results would be applicable and relevant to as many manufacturers as possible (4). As a broad supplier to many of the consortium's members, Avantor was selected, among other companies, to participate in the pilot. Avantor was the first supplier to have availability to host an audit, which was conducted in April 2011.

The Avantor audit

Rx–360's Auditor Qualification Working Group selected the third-party, accredited auditors based on a rigorous selection process. Criteria included education and experience with GMP products and training. Two auditors spent two days at Avantor's Phillipsburg manufacturing facility. Four quality department managers from the Avantor site were involved in the audit. In addition, the auditors engaged with additional company experts (e.g., senior validation manager, plant manager, global director of procurement) as needed. The focus of the audit was on the facility's production and shipment of pharmaceutical excipients as well as several highly regulated products: benzyl alcohol; potassium phosphate and potassium nitrate; and hydrochloric acid.

The Phillipsburg plant hosts 40 to 50 audits each year, with each industry audit averaging one day. Using Rx–360's standards, the audit included an evaluation of site security, quality-management procedures, manufacturing operations, packaging and labeling processes, information-technology security, and organization and personnel awareness (2, 3). After receiving an overview of Avantor's quality systems, the auditors toured the Phillipsburg plant. They were shown the complete processes and procedures for the four chemicals noted above, from receiving raw materials through to packaging and shipping final product. The auditors reviewed batch-production records and analytical-testing procedures for packaged material in its final form to ensure for the consistency, quality, and stability on several lots of product. In addition, the auditors reviewed facility documentation to search for any nonconformances. Staff-training records as well as maintenance and calibration records for processes and equipment were also reviewed. Within 30 days of the audit, Rx–360 provided Avantor with a report stating that the company has completed the audit with no critical observations. Rx–360 has since shared the audit with its members.

Lessons learned and the future of Rx–360

Rx–360 expects to audit more facilities as part of its pilot audit program, which will be completed by early 2012. The audit reports and program results will be closely examined by members of the consortium to determine the final qualifications of a standardized procedure for future audits (4). The audit was beneficial because it allowed Avantor to view its manufacturing processes through a lens that combined most industry audit standards into one comprehensive and stringent audit. Avantor is pleased to have completed the audit with no critical findings. Once the pilot is complete, the consortium will focus on amassing a repository of audits for the industry to share, with the goal that manufacturers can replace individual audits with those conducted by Rx–360 (4). In the long run, suppliers and manufacturers will ideally be able to invest more time and resources into advancing security.

Paul Smaltz is executive vice-president for Pharmaceuticals and the Americas at Avantor and an Rx–360 Board Member. Rick Siberski is global director of Quality Assurance and a member of the Rx-360 Auditor Qualification Working Group.

References

1. Rx–360 website, www.rx-360.org, accessed July 8, 2011.

2. Excipact, Draft Excipient GMP Standard, April 2011.

3. IPEC/PQG, GMP Audit Guide for Pharmaceutical Excipients (2007).

4. Information according to Rx–360 Chair Lynne Byers.

Read a whitepaper from Avantor on this subject (PDF).