By Greg Dombal, managing director of Halloran Consulting Group and Elizabeth Schaul, business operations associate at Halloran Consulting Group
In planning for and selecting a program’s contract manufacturing facility, it is worth considering some of the characteristics that have been previously established for manufacturing plants of novel products. Genzyme, Biogen, and Amgen all established dedicated production facilities to support their lead products. On the surface, it might be easy to conclude that the primary feature of success in the manufacturing sphere was the ability of these companies to establish their own dedicated facilities. In reality, however, the success of the initial products was likely a combination of the manufacturing efforts as part of a larger, fully integrated, and thriving product-development program. In effect, these facilities — with dedicated utilities, unique training programs, and their own engineering and quality staffs — were early CMOs, and they laid the groundwork for identifying the key attributes of a thriving and productive contract manufacturing facility today.
The core of any successful manufacturing facility is strong technical competence. Competence in a manufacturing operation extends beyond “just having done it” and is not effectively captured in the idea that “we have manufactured several products like this; therefore we also know how to successfully manufacture this product.” Instead, competence is the ability to evaluate the process and product from a combined biologic, chemical, and engineering perspective. A very good indicator of a technically competent manufacturing operation, especially that of a nonsmall molecule product, is how deeply within the organization the process development and/or product monograph is shared. Commitments to technical competence by a CMO will frequently require that the product characteristics and supporting data that define processing parameters be disseminated to engineering and quality assurance, in addition to processing staff. The more breadth and depth with which the product characteristics and supporting data are shared within the organization, the greater the likelihood of the CMO possessing stronger technical competence.
The presence of program management is a second key attribute of a successful CMO. In the case of smaller-sized CMOs, a strong program management staff may exist, and in the case of larger CMOs, a vertically integrated program management culture may be required. In either case, it is critical to manage the sequencing of activities and dependencies of key tasks (and possibly resources) to ensure a manufacturing campaign that lasts months — if not years — will avoid costly lags in activity. For illustration, CMOs operate on a cycle from contract signature to production, ranging from as short as several weeks to as long as 9 to 12 months. Everything from raw materials, facility availability, and customer requirements affects these cycles. However, a strong program management presence will interrogate the timeline, regardless of its length, and ensure that activities including sourcing supplies and raw materials, adopting methods, conducting site evaluations and audits, facility of equipment cleaning/validation/qualification, and other logistics are documented and understood. This significantly increases the likelihood the CMO will meet the agreed-upon timelines — both from increasing internal knowledge of the process and from helping the sponsor understand the timeline’s parameters.
The final key attribute is an integrated quality assurance and engineering function. As worldwide regulatory bodies have increased their enforcement efforts, it has become increasingly important to document changes with complete rationale and risk management assessments. There must be transparency as to why changes have been made, regardless of how inconsequential they may seem. A commitment to change control and continuous improvement is the functional result of an integrated approach to quality. Every member of a project team likes to think that they “know” the process and is certain which changes to processing parameters are of potential consequence. However, it is our experience that no two manufacturing runs are identical in every fashion — whether there are different operators or different batches of active agents, each run is always unique. As such, changes and modifications should be expected, and it is essential that a company respects the importance of recognizing changes, communicating their existence, evaluating their impacts or lack thereof, and documenting the entire process. A clear documentation trail and proactive communication with the sponsor will help avoid process deviations, production failures, and regulatory questions and ultimately will ensure the CMO is successful.