Preparing Documentation to Support Clinical Supply Manufacture - Pharmaceutical Technology

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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.


Pharmaceutical Technology


A written report of the outcome of the technical assessment is recommended by one clinical manufacturing representative in conjunction with the formulator. This report, filed in a retrieval location within the representative's company, provides colleagues the opportunity to review the contractor's capabilities for this project and future projects. A positive technical assessment grants the go-ahead for the quality assurance (QA) audit. If the assessment is negative, then the decision may be to suggest remediation steps or evaluate another contract facility.

The clinical manufacturing representative who performs the technical assessment also should attend the clinical manufactures at the contract facility. This representative is the contact person who should work firsthand with the contractor in planning, executing, and following through to manufacturing completion.

QA audit

If questionable issues arise during the technical assessment, then a request can be made to the sponsor's QA representative to address these concerns in an audit. The technical assessment and QA audit may be performed simultaneously. Nonetheless, the purpose of performing the technical assessment before the QA audit is to ensure that the contractor has the capabilities to perform the manufacture. If the contractor does not meet manufacturing requirements, then there is no reason to pursue a relationship with the contractor for this project.


Table III: Quality assurance audit.
The sponsor's QA department arranges with the contractor's QA department to conduct a facility inspection. This CGMP audit includes but is not limited to an inspection of the building and company operations. This inspection also should include an audit of the departments with which the product will come in contact such as the warehouse, manufacturing areas, packaging areas, quality control (QC), and analytical laboratories. In addition, the review of personnel training files, standard operating procedures (SOPs), equipment validation reports, equipment cleaning validation, and equipment calibration programs are subject to inspection. Another area of concern is how the contractor maintains the sponsor's confidentiality when other clients are in the contractor's facility performing audits and observing manufactures (see Table III).

At the conclusion of the inspection, the QA auditor conducts an exit meeting with those representatives who participated in the inspection. The exit meeting summarizes the observations of the auditor during the inspection. Inspections typically last a day and a half or longer, depending on the size of the facility, level of CGMP compliance at the contractor site, the length of time it takes for the contractor to retrieve requested information, and the number of departments that are inspected. Observations should be discussed as they are noted during the audit and agreement reached before the exit meeting. During the exit meeting, the auditor notes issues that already may have been addressed and corrected. The QA auditor then approves or denies the use of the facility. If appropriate, the auditor may conditionally approve the facility with stipulations such as:

  • Only particular equipment may be used
  • Manufacturing operations may only be conducted in a particular manufacturing area
  • Additional testing of raw materials may be required
  • Special requests may be made regarding the operations (e.g., a representative from the sponsor's company must be on-site during batch manufactures).

As a follow-up, the QA auditor issues a written report to the contractor detailing observations that were discussed during the exit meeting. In turn, the contractor responds to the observations in writing. The contractor's response should include the corrective action to take place with a timeline for implementation, or the contractor may reply that the current procedure is acceptable and include a justification for this decision. If the contractor's response is unacceptable and the observation is deemed critical, then the status of the contractor may change.

Contract facilities are usually very flexible and, within reason, special requests can be handled. After all, the contractor wants the pharmaceutical company's business and if it is making the request, chances are another client will do the same. In addition, the QA auditor often identifies the contractor's weaknesses, and it may be to the contractor's advantage to reevaluate its operations.


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