The primary objective of the audit is to ensure that clinical supplies will be manufactured under CGMP requirements and to
the sponsor's expectations. Of course, this objective requires that the expectations be reasonable and that the sponsor only
require of the contractor what it requires of its own company. Many companies expect the contractor to go far above a CGMP
requirement because they are a paying customer. Such situations do not build good relationships. Remember that the sponsor
and the contractor are a team working toward the same objective. Both companies are building a working relationship that will
last not only for this but also for future projects.
Once your QA department approves the contract facility for use, a quality agreement is prepared by the sponsor's or contractor's
QA department. A quality agreement defines the responsibilities of both companies for clinical supplies manufacturing, testing,
packaging, and distribution of a specific product.
The quality agreement identifies the party responsible for maintaining regulatory and CGMP compliance. Additional responsibilities
are outlined for the maintenance of specifications, procurement, storage, sampling, testing and release of raw materials,
API, and packaging components (see Table IV). The quality agreement also specifies the party responsible for ensuring that
the product complies with the approved product specifications. The role of the contractor's QA department, which is to review
and approve the batch record documentation and analytical testing results, should also be stated in the quality agreement
(9, 10). The quality agreement is reviewed by the sponsor's and the contractor's legal department and requires signature approval
by senior management, including senior management in QA at the contractor's and sponsor's sites.
Table IV: Quality agreement.
The clinical supply agreement also is an important document that focuses on the activities that the contractor will perform
for the sponsor during the manufacture of clinical supplies. When the contractor requires formulation-development work before
clinical supplies are manufactured, the contractor's legal department prepares a development of a manufacturing agreement.
The type of agreement required depends on the activities the contractor will perform and the legal requirements of the sponsor
and contractor. These agreements capture the business relationship between the contractor and sponsor, whereas the quality
agreement captures the quality aspects of the product to be manufactured.
Clinical manufacturing representatives should be aware that these agreements may be required at their companies and that the
company may request that they review the agreements before the start of operations. Writing these agreements may be initiated
by the project manager or the business development group at the sponsor company, depending on the sponsor's internal procedures.
As applicable, these agreements should be reviewed by the sponsor's legal, QA, analytical, formulation development, clinical
manufacturing, and purchasing departments. Most important, the clinical manufacturing representative can ensure that all departments
that provide input to these agreements are involved at the onset of the writing of these agreements. These agreements are
approved and signed by senior management at both companies.
Once there is a clear understanding of the manufacturing operation and what the sponsor is requesting, the contractor's technical
group may prepare a manufacturing protocol. The manufacturing protocol includes the scope of the project and details the contractor's
manufacturing responsibilities regarding the product. This document also becomes a guideline for writing the batch manufacturing
record (BMR). The protocol identifies the product to be manufactured, the quantity to be manufactured, and, if applicable,
the dimensions of the product, including imprinting or embossing for tablets or capsules (see Table V).
Table V: Manufacturing protocol.
The protocol also specifies whether the raw materials tested by the contractor meet United States Pharmacopeia–National Formulary (USP–NF), European Pharmacopeia (EP), and Japanese Pharmacopeia (JP) monographs, as applicable.