A Official requirements
In Europe, the head of production is responsible for validation within the manu- facturing area. In accordance with §2.5 and 2.7 EU GMP Guide, he must ensure that the necessary validations of manufacturing procedures are carried out. The written instructions and operating procedures (manufacturing instructions) which are compiled under his responsibility form the basis of process validation. These documents must conform to the marketing authorization/registration doc- uments. Responsibilities should be clearly defined, if other internal areas (e.g. Engineering, Research&Development) are involved in the validation.
A written contract must be drawn up between the contract giver and the con- tract acceptor, if the task of process validation is transferred to third parties (EU GMP Guide §7.1). The contract must clearly define the responsibilities of both sides, and in particular regulate compliance with good manufacturing practice. The contract giver must ensure that the contract acceptor carries out the task in line with the instructions given. Transferring the task of process validation to external service providers does not change regulations concerning responsibility in line with EU GMP Guide in any way: the head of manufacturing can transfer the execution of, but not the responsibility for process validation. This means that he retains the legal and public responsibility for completing all validation work in line with regulations in his area.
The holder of the manufacturing authorization is responsible for ensuring that key personnel are able to carry out their duties in compliance with the regula- tions. In accordance with EU GMP Guide §2.2, he must bestow sufficient authority on staff in leading or responsible roles to enable them to meet the demands of their tasks. He must, therefore, make the necessary organizational arrangements (organizational diagrams and job descriptions) and provide the necessary utilities.
For compliance under United States laws and regulations, the firm holding the approvals and filings is legally responsible. The expectations and general requirements for validation are similar to the EU with the exception that the spe- cific person responsible for performing the validation is more flexible. The head of the appropriate organizational unit is responsible for assuring that validations are conducted and properly documented with the documented review and approval of the quality unit. The president or most senior manager/director of the firm is ultimately held accountable for all CGMP compliance requirements. Contracts and agreements can be executed to assign defined responsibilities for activities associated with validation; however, the ultimate direct responsibility always remains with the application holder and the firm’s quality unit. Under USA law, FDA expects and holds the drug application holder responsible for these regula- tory responsibilities and they cannot be delegated to a third party.
M. Hiob / M. Lazar
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