Preparing Documentation to Support Clinical Supply Manufacture

This article is written to assist clinical manufacturing representatives at pharmaceutical companies who are faced for the first time with outsourcing the manufacture of clinical supplies. The author describes the identification, writing, and execution of documents required to support the contract manufacture of products for clinical studies.
Aug 01, 2007
Volume 2007 Supplement, Issue 3

Interactions between a sponsor and a contractor before and during the clinical manufacture of a drug product should involve discussions about responsibilities, current good manufacturing practices (CGMPs), regulatory requirements, and company operations. Documenting this information ensures both parties have a clear understanding of their roles and how the manufacturing operation will be conducted. The preparation and the ability of both parties to understand and agree upon their responsibilities in writing before the start of manufacture leads to a smooth and successful operation.

The task of identifying the contract manufacturing organization (CMO)is beyond the scope of this article. Information about CMO selection may be available through networking with pharmaceutical colleagues or in trade journals (1–5).

Confidentiality agreement

Once a contract facility is identified, a confidentiality agreement, also known as a nondisclosure agreement, is prepared by the sponsor's or the contractor's legal department before any exchange of information. When the confidentiality agreement is written by the sponsor, the agreement is forwarded to the contractor's legal department for review. If both companies differ on the content of the agreement, they negotiate the terms until a signed agreement is executed. The confidentiality agreement may be written by the contractor when the sponsor does not have a department that writes confidentiality agreements (e.g., a small start-up company).

The agreement must be a bilateral confidential disclosure agreement. This type of agreement provides for the sharing of information on a confidential basis between both companies. Both parties agree not to disclose the other's proprietary information to any third parties other than affiliated companies and consultancy firms that are bound to the terms of the confidentiality agreement.

Table I: Confidentiality agreement.
Confidential information should include all proprietary technical, nontechnical, and commercial information marked "confidential" or declared to be confidential by the disclosing party and given to the receiving party. The length of time this agreement should be in place also is specified (see Table I).

The confidentiality agreement is approved and signed by senior management at both companies. Confirmation of an executed confidentiality agreement by the clinical manufacturing representative is important before exchanging information about the active pharmaceutical ingredient (API), drug product, and manufacturing operation and performing a CGMP audit with the contractor.

Technical assessment

After the confidentiality agreement is signed, a technical assessment of the contract facility is recommended. The technical assessment can be performed by the clinical manufacturing representative and the formulator.

Table II: Technical assessment.
A technical assessment ensures the contractor has the type of equipment required to manufacture the batch, the ability to handle the batch size, and the technical expertise to manufacture the dosage form. In addition, a technical assessment includes evaluation of the batch record documentation and processing operations with respect to the product that will be manufactured (see Table II).

Of course, the most important aspect is to get a feeling for the type of working relationship the sponsor and the contractor will have (6). A good working relationship is especially important when the sponsor's long-term goal is to commercially manufacture the new drug product at the contract facility. This project involves the two companies working together through manufacturing clinical supplies, registration batches, technology transfer, process validation (7), and the US Food and Drug Administration preapproval inspection (8).

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