Allow time for thorough upfront product and project evaluation. Regulatory departments from the sponsor company and the CMO
must know how the product fits into the CMO's facility—that is, ask whether the product is a cell-line or animal derivative
and how it affects the other sponsor-company products produced at the facility. Also, ask how the CMO communicates change
control, whether the CMO has an online notification system, and how involved the CMO regulatory department will be. A good
CMO can provide a piece of or the entire CMC section.
The quality-management process begins in earnest with the quality audit. Sponsor companies should send representatives who
are familiar with the project with their auditors. Many companies have separate auditing departments, and sending someone
who knows the project with the auditors enables the sponsor company to receive project-specific quality answers. CMOs should
provide meaningful audit support. Audits function best when both sides are prepared with questions and the appropriate documentation
to demonstrate they know and understand the project scope with all of its requirements.
As the project progresses, carefully manage the regulatory and validation strategy. This task is best handled by first understanding
the phase requirements, then setting expectations based on the sponsor company's risk tolerance. For example, full process
validation is not required for Phase I clinical-trial material production. Method validation, however, is required for stability-indicating
assays where expiration dating depends on proof of shelf life. Knowing phase requirements gives both the CMO and the sponsor
company a high degree of flexibility in scheduling validation runs, media fills, and so forth and can save time and money
throughout the life of the project.
Risk tolerance will ultimately dictate the final regulatory and validation strategy. The conservative approach involves performing
validation work earlier in the project and allowing for changes. Deadlines (patent dates) do not always allow for a conservative
approach, thereby requiring a balance between risk and requirements.
Both the sponsor company and the CMO must go into the project knowing and sharing their risk tolerances. CMOs have a direct
influence on product quality. Product responsibility belongs to the sponsor company but preapproval inspection reports belong
to the CMO. Both must work together to guarantee success.
Quality control and method transfers.
The main element of quality control when using a CMO is method transfer. If handled carefully and with strict attention to
details and timelines, method transfer can be successfully completed and provide the support necessary to meet production
and regulatory filing requirements.
Before method transfer begins, take the time to learn each quality group's language and syntax. The quality groups include
the sponsor company, CMO, and third-party laboratory, when involved. Ensure there is a clear understanding of how the terms
qualification, technical transfer, and validation are used at each facility involved. For example, when talking about method validation does it mean full ICH validation? A
full information exchange of all available information is critical for timely method transfers. Whenever possible, always
provide validation packages to the CMO.
CMOs should train sponsor companies. Fully explain the method-transfer process at the CMO facility. Don't assume everyone
follows the same steps taken during the transfer process.
Method transfer is critical and solely based on method status. If methods are fully validated, robust, and well documented,
a competent quality-control laboratory will have no problem with the transfer process. Problems abound, however, when method
development is not complete or done at a non-GMP third-party laboratory. Know and understand where the methods are in the
validation process. Does the CMO need to provide method validation or development? If so, allow enough time for contingencies.
Another issue that frequently plagues quality-control labs is the availability of reference standards. If these standards
are from sources overseas, determine how shipping requirements will affect the standards. Can standards sit in customs for
two or three weeks and still be viable? Is the reference standard really a primary or secondary reference standard, and not
another lot of API needed for use later? Take the time to know and understand where the methods and reference standards are
and provide all the information to the CMO.