Variable B: compliance needs.
Multiple customers, regulatory agencies, and standard-setting organizations influence compliance requirements maintained
by a CMO. Each requirement needs to be implemented to accommodate the broad spectrum of these influences. Variable B of the
equation defines the compliance needs for the manufacture of all products at the given facility. Company standard operating
procedures (SOPs), customer SOPs, audit observations, and compendial requirements need to be considered in discussion with
the client and the CMO. Clients should make every effort to understand their CMO's SOPs.
It is equally important for the CMO to make sure that its SOPs are robust enough to accommodate multiple clients' needs. It
is difficult for a CMO with multiple clients to operate using duplicate SOPs for the same process or procedure. The CMO and
the client should therefore spend a sufficient amount of time ensuring that the compliance needs of both parties are defined
and met.
Similar to variable A, variable B also has an audit element to consider. In this case, the effectiveness and appropriateness
of a CMO's audit program is considered. The audit program must meet the regulatory expectations for internal and supplier
audits while also meeting the client's expectations on these points.
In addition to these audit requirements, the CMO and the client must discuss the communication expectations for regulatory
audits either conducted at the CMO's or the client's place of business. The need for the CMO to communicate with the client
when a regulatory audit is being conducted at their facility is evident but it is equally important that the client communicate
with the CMO when the positions are reversed. Two-way communication is crucial because each organization could be vulnerable
for a regulatory audit based on the outcome of the regulatory audit being conducted at either facility.
In addition to SOPs and audit requirements, compliance to the compendia must be considered under variable B. The client should
confirm that the CMO has a process in place for reviewing and updating test procedures to maintain compliance with the applicable
monographs, test chapters, and informational chapters maintained by the United States, Japanese, and European pharmacopeial
authorities.
Variable C: client needs.
Customers bring requirements to the table that may be needed due to factors that are not within the purview of the CMO. These
requirements might be influenced by development data, regulatory registration commitments, sourcing strategies, or partnerships.
Under variable C, the CMO must consider the needs of the client in order to effectively provide them service. For example,
the phase of drug-product development and whether the client is virtual or has in-house capabilities are elements that may
affect the allocation of responsibilities within the Quality Agreement. If the product is under a cooperative arrangement
with multiple companies, there may be more than one Quality Agreement associated with the manufacturing, packaging, and labeling
of the product.
If this is the case, the client should let the CMO know of these agreements and of the expectations when the product is passed
to another responsible party during the manufacturing process. In addition, it is important that the client communicate with
the CMO whether another contract provider is having regulatory difficulties. Finally, the client and the CMO need to determine
whether any special testing protocols are needed for products in Phase 2 or 3 of the development process. If the testing of
excipients used in the product is being performed by another organization other than the CMO client, this fact should be disclosed
to ensure that excipient compendial requirements are met. The same situation is important with regard to where the material
is sourced—whether it be a single source or multiple sources.
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