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Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.
Key talks from the recent PDA/FDA regulatory conference highlight room for improvement.
The relationship between a client and a contract provider is important and complex. At the recent PDA/FDA Joint Regulatory Conference, held Sept. 10–12 in Baltimore, participants were treated to an in-depth look at this multifaceted alliance.
Susan J. Schniepp
E.J. Brandreth, vice-president of quality and regulatory affairs for Althea, offered a CMO's perspective of this relationship. In his presentation, Brandreth stressed the significance for a contract provider to be as knowledgeable and up-to-date on the application and interpretation of the regulations as the drug product sponsor. He educated the audience on various sources that contract providers use to establish robust processes that meet the needs of providing safe medications for multiple clients who have products ranging from Phase I to commercialization. These sources include guidelines and reports from PDA, the International Conference on Harmonization (ICH), the US Pharmaceopeia (USP), and The Gold Sheet. He also raised a thought-provoking concept: that reputable CMOs have some of the most robust and compliant systems because of the frequency that clients and regulatory agencies—both domestic and foreign—audit them. Although time-consuming, these audits allow contract providers to benchmark against best practices and the cumulative knowledge of the auditors. Brandreth's presentation also discussed the ideal relationship between the two parties as one in which the CMO and sponsor work together to achieve success. Ultimately, a CMO needs to think of itself as an extension of the sponsor.
CMOs are acutely aware of the concerns of their sponsors because they are documented through audit observations, but it is not often that the complaints of CMOs are voiced. Brandreth eloquently brought to light the biggest complaints of the average CMO: unrealistic timelines, skipping engineering runs, and trying to overcome major scientific limitations during the knowledge-transfer process. Finally, Brandreth unified the client–contract provider relationship by noting that both parties face the same emerging issues, including glass delamination, weak investigations, and insufficient corrective and preventive action programs.
Christopher Masterson, senior director of quality for Cubist Pharmaceuticals, spoke as well, from the point of view of a contract provider. He shared with the PDA/FDA audience the problem that there are too many immature client–provider relationships. He iterated the numerous contract services available today, including providers for cell banks, drug substance manufacturing, drug product manufacturing, R&D, test laboratories, labelers, and distributors.
There has been much discussion in the industry that guidance on client–provider relationships is needed. In his presentation, Masterson pointed out that guidance does exist and cited a little-known regulation that currently addresses contract facilities: 21 CFR 200.10. This regulation states that FDA "regards extramural facilities as an extension of the manufacturer's own facility." Additionally, the regulation goes on to say,
"The Food and Drug Administration reserves the right to disclose to the pharmaceutical manufacturer...any information obtained during the inspection of an extramural facility having a specific bearing on the compliance of the manufacturer's, applicant's, or sponsor's product with the Federal Food, Drug, and Cosmetic Act."
Based on this regulation, Masterson provided concrete examples of some activities the client–service provider should consider in its relationship to demonstrate compliance to this regulation. Some suggestions include visits with the service provider (beyond the traditional annual GMP audit), establishing key performance indicators, participating in material-review board meetings as needed, performing joint investigations as needed, and sharing issues through regularly scheduled business review meetings. Masterson demonstrated the success of this approach by sharing some case studies in which the client and service provider worked together to turn potentially negative situations into positive outcomes. He concluded his presentation by advising the audience to use data, science, and logic to solve problems and that the goal of the client–provider relationship is "not to think alike but to think together."
Allan Coukell, director of the Medical Programs Pew Health Group at The Pew Charitable Trusts, provided a global perspective on this issue. He pointed out that outsourcing has grown exponentially over the past 10 years, complicating the already complicated pharmaceutical supply chain. In discussing this complexity, he brought to light some disturbing facts, including that FDA 483 observations to contract manufacturers have risen over the past three years. In addition, Coukell noted that "FDA has expressed concerns about deficiencies in supplier qualification programs and quality agreements and that current regulations do not require companies to assess supplier plants before purchasing ingredients from them, or to visit the plants at any time to ensure quality standards are in place." He further highlighted the steps being taken to address this gap in regulations through the passage of new laws such as the 2012 FDA Safety and Innovation Act (FDASIA) and Generic Drug User Fee Amendment (GDUFA). He also complimented industry on some of its initiatives aimed at resolving supply-chain issues, including the efforts of Rx-360 (the international pharmaceutical supply chain consortium), EXCiPACT (a voluntary international scheme to provide independent third-party certification of manufacturers, suppliers, and distributors of pharmaceutical excipients worldwide), and International Pharmaceutical Excipient Auditing (IPEA), which also provides third-party audits through a shared audit program and ANSI accredited certification program.
It is important for industry to understand and work to improve their client–service provider relationships. Such re-evaluations make both sponsors and CMOs more effective in achieving the goal of improving public health and safety.
Susan J. Schniepp is vice-president of Quality and Regulatory Affairs at Allergy Laboratories, Oklahoma City, OK 73109. Tel. 405.235.1451, firstname.lastname@example.org.