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
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.
Variable D: regulatory commitments. Regulatory commitments are an evolving body of knowledge that may necessitate flexibility to adapt to CMO and client interpretations
of new or impending regulations. Variable D considers the regulatory commitments of the client and/or the CMO. CMOs can indicate
which regulatory authorities have audited their facilities, when they were last audited, and the outcome of these audits.
A CMO must also communicate to their clients the changes and commitments made to their Quality Systems based on the responses
to the regulatory audits because these changes may affect the regulatory filings of the clients. Each client will have its
own interpretation of how to comply with the audit observation and what filing strategy should be used to update their filings,
The CMO must ensure that its responses to regulatory audits do not jeopardize any of their clients' commitments. On the other
hand, clients must communicate with the CMO regarding commitments they have made in their registrations. Among other information,
they should disclose to the CMO whether they are using novel excipients as opposed to compendial excipients and whether any
special specifications or testing must be performed.
Variable E: The Quality Agreement. The solution to the equation noted above (A+B+C+D) is E, which represents Quality as a function of product lifecycle. The
document that contains the information defining the various responsibilities that comprise E is the Quality Agreement. This
master document should define the CMO's needs, the client's needs, the compliance needs for the product and both parties,
and any pertinent regulatory commitments. The Quality Agreement should be a living document that is reviewed and revised as
often as needed to clarify the responsibilities of the client and the CMO as the product progresses through its lifecycle.
The Quality Agreement is akin to a marriage license between two parties and should clearly identify the roles and responsibilities
needed for a successful partnership.
In general, Quality Agree-ments are legally binding agreements between the Quality functions of the contract provider and
the contract giver. Many companies use a matrix approach for defining these activities which can include but are not limited
to compliance, manufacturing, packaging and labeling, documentation, change control, nonconformance, out of specification
(OOS), deviations, complaints, recalls, and auditing. Each document should be tailored to address the expectations of the
specific operations to be undertaken by the CMO as well as external actions that may have an impact on those operations. Clients
and CMOs should communicate frequently to make sure that the product being manufactured meets the necessary specifications
required to meet the minimum Quality requirements. In order for the relationship between the client and the CMO to be effective,
the two parties should communicate often.
Defining the Quality relationship between a CMO and a client is complex and requires extensive discussion and attention to
detail. The relationship should be open and communication between the two parties should be as frequent as required to assure
that the product being manufactured meets the highest Quality standards for the client and for the patients.
SUSAN J. SCHNIEPP is vice-president of Quality at OSO Biopharmaceuticals, firstname.lastname@example.org