The Rx-360 consortium has had a profoundly positive impact on pharmaceutical manufacturers and their suppliers. As an international, nonprofit, pharmaceutical supply chain group (established in 2009), its mission is to “create and monitor a global quality system that meets the expectations of industry and regulators that assures patient safety by enhancing product quality and authenticity throughout the supply chain” (1).
The list of consortium members (www.rx-360.org/Membership/ListofMembers/tabid/71/Default.aspx) is diverse and presently includes both pharmaceutical manufacturers and suppliers (24 and 30 companies, respectively, as of June 2012). Auditors, regulatory agencies, and professional trade organizations may participate as observers. Rx-360 actively engages with global regulatory agencies such as the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), the World Health Organization (WHO), the European Directorate for the Quality of Medicines & Healthcare (EDQM), and the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) (2).
Joint Audit Program
The Rx-360 consortium established its Joint Audit Program to ease the audit burden for both drug manufacturers and their suppliers, while maintaining rigorous quality standards that meet the expectations of all members and regulators. Joint audits of a supplier are conducted upon request by an Rx-360 member company. That request is submitted to the Rx-360 secretariat, who reaches informs members that a joint audit request was submitted and polls them to determine whether others would like to also sponsor the audit. If no other members are interested, then the audit proceeds with only the single initial requestor. Audits within the program are conducted
by the consortium’s qualified third-party auditors. Designated third-party auditors must meet requirements set forth by Rx-360 members and must have a recognized certification or accreditation. Rx-360 members have agreed on minimum requirements for third-party auditors. They also have generated audit templates — based on input from drug manufacturers and suppliers — to ensure a consistent audit and final reporting approach. Once an audit is complete, the final report and all resolutions or responses are available for purchase from the consortium.
Program Advantages: As a supplier, GE Healthcare believes that the Joint Audit Program offers a number of benefits. The GE Healthcare Life Sciences site in Uppsala, Sweden is audited frequently because of the critical nature of its products in the purification of biopharmaceuticals. The volume of requests for site audits can at times result in longer-than-expected lead times for scheduling an audit. GE expects the Joint Audit Program will reduce its site audit burden and subsequently improve its ability to schedule and host audits within specific timeframes for our customers.
Conducting audits is costly and resource-intensive for all involved parties. Reducing overall expenses dedicated for such a process can be beneficial for very small to very large companies — manufacturers and their suppliers alike. Using the Joint Audit Program allows companies to leverage best industry practices and to use highly skilled auditors with extensive experience. It also provides access to audit templates that have been derived through consensus from many pharmaceutical companies, auditors, and suppliers.
Regulatory Support: Many companies have hesitated to take full advantage of shared or joint audits because of concerns over how regulators may perceive the practice. In 2012, however, the EMA and the FDA launched a three-year pilot program to share work on facility inspections in each other’s territories. As the EMA has noted, this strategy will enable both authorities to “rely on each other’s inspection outcomes rather than carrying out separate inspections in duplicate” (3). In a joint document explaining the decision, both agencies agreed that “Authorities from both regions have recognized the potential resource efficiencies to be gained from progression beyond existing collaborative projects towards reliance on each other’s inspection outcomes” (4). The EMA and the FDA also previously held a two-year (December 2008 to December 2010) pilot inspection program with the Australian Therapeutic Goods Administration on active pharmaceutical ingredient manufacturing facilities.
Regulators recognize the benefits of shared or joint audits, assuming those audits are conducted by qualified persons who can sufficiently assess the quality practices of a site. Richard L. Friedman (director of the Division of Manufacturing and Product Quality in the Center for Drug Evaluation and Research, in the FDA’s Office of Compliance) has said, “FDA is very much in favor of industry’s cooperative efforts, such as Rx-360. .. .” He also stated that, “anytime we see these kinds of collaborative approaches by industry, we’re very heartened by them” (5).
Supplier Perspective: GE Healthcare has been a member of Rx-360 since August 2009 and has participated in the Audit Standards Working Group. Specifically, we contributed to the Basic Chemicals and Raw Materials Audit Guide as well as the creation of an appendix specific to chromatography resins. It has been very valuable as a supplier to be able to participate in and support the development of audit standards. Through the consortium’s collaborative process, we obtained a better understanding of an Rx-360 member’s areas of focus, interest, and quality concerns. GE also had the opportunity to share a supplier’s expertise and perspective on proposed requirements.
For a supplier, one potential concern related to joint auditing is availability of confidential information or other intellectual property (IP) to competitors. Rx-360 has implemented measures to sufficiently protect IP for all parties. Suppliers have the option to deny any company’s access to audit reports, and audit information is shared only under the conditions of a confidentiality agreement.
Pilot Audit Program
The GE Healthcare Life Sciences site in Uppsala, Sweden, was fortunate to participate in the pilot audit program, a testing period for the Joint Audit Program processes and procedures. The objective of this pilot audit was to evaluate the facility and manufacturing operation against the Rx-360 Audit Guide for Chromatography Resins and the Audit Guide for Basic Chemicals and Raw Materials. The audit was conducted over two days by two qualified auditors. It primarily focused on the activities and quality-management systems involved in manufacturing, packaging, testing, and distribution of chromatography resin products. It also included an evaluation of supply chain security.
The use of qualified third-party auditors ensured that the audit was effective and efficient and that audit standards were applied consistently across all functional areas of the business. This practice sh
ould ensure consistent and unbiased application of audit standards to all suppliers. Auditors demonstrated appropriate expertise, skills, training, and motivation, and they were very diligent, dedicated, and engaged in the process. They were astute in evaluating the broad quality system and site specific manufacturing and were transparent when communicating systematic issues and identifying gaps or weaknesses in our processes. This feedback was given throughout the audit, which gave us an opportunity to discuss the findings and provide further clarification, when necessary.
Auditors tend to focus on areas that are aligned with their background or expertise. Most will spend a significant amount of time on one functional area, for example microbiology or engineering practices, while limiting the time spent on other functional areas or a broad quality system. Contrary to such experience, the Rx-360 qualified auditors covered all aspects of the site systems and products with equally detailed and thorough methods. We consider all audit findings and observations to be opportunities and strong drivers toward improving our quality system, and we were engaged and motivated by the interactions with the third-party auditors.
At the closing meeting, the final audit observations were presented, discussed, and approved. The auditors sent a draft report to be reviewed for correction of potential errors or misunderstandings. The final report was distributed within 20 working days after the audit and required a response by GE Healthcare within 15 working days. Communication with the auditors was open and professional during the process, and the team wrote a comprehensive and informative report. The final audit report and response were completed within the requested time frame, and additional questions required by Rx-360 were communicated through e-mail and finalized within three months from the audit. The final audit report provides sufficient information to Rx-360 members to ensure confidence in the result and confidence in GE Healthcare as a supplier.
Easing the Audit Burden
The Rx-360 consortium has increased quality of audit performance through standardized supplier requirements, use of qualified and professional auditors, and focus on relevant findings. Decreasing the number of audits at a supplier site while increasing audit effectiveness reduces the burden on a supplier. Availability of a high-quality audit report benefits end users as well. Joint audit reports can be purchased upon supplier approval and completion of a confidentiality agreement. We consider the Shared and Joint Audit Programs to be an overall win for the pharmaceutical industry as a whole.
GE Healthcare Life Sciences would welcome the opportunity for sponsorship of audits at its other manufacturing sites in Umeå, Sweden and Westborough, MA (United States).
Corresponding author Lauren Melton is a strategic regulatory marketing director, and Christine Wahlgren is QA manager, both of GE Healthcare; 1-508 616-3054; firstname.lastname@example.org.