Manufacturing Information documentation Manufacturability review

The excipient manufacturer should develop plans that identify the responsibility for each design and development activity which is updated as necessary. Organizational and technical interfaces between different groups should be identified and the necessary information documented, transmitted and regularly reviewed. 

Most hydraulic fluid preparations start as chemical mixtures. For instance, there is a considerable area of overlap in the specific petroleum hydrocarbon chemicals contained in the mineral oil and polyalphaolefin hydraulic fluids. For all classes of hydraulic fluids, there may be similarities with other original products intended for use as lubricants. The complications involved in documenting the environmental fate of mixtures increase under conditions encountered at many NPL sites, where it may be hard to determine the precise original product associated with chemicals identified at an area in need of remediation. In most instances, available peer-reviewed literature, supplemented with data obtained from manufacturers of particular formulations and information in trade magazines, can supply information about the original hydraulic fluid preparations. At NPL sites, site-specific evaluations of specific chemicals may be the only feasible way to address concerns over environmental fate and potential exposure risks. 

Information from pharmaceutical development studies can be the basis for risk management when these studies are designed with the aim of demonstrating that quality was built in by design. This document and the manufacturing science framework provide an area of common interest and opportunity for collaboration between the CMC review and CGMP investigations staff. 

A fundamental objective of a computer system applied to automate a pharmaceutical GMP operation is to ensure the quality attributes of the drug product are upheld throughout the manufacturing process. It is therefore important that quality-critical parameters are determined and approved early in the validation life cycle. The exercise should be undertaken to a written procedure with base information from the master product/production record file examined and quality-critical parameter values and limits documented and approved for the process and its operation. In addition, the process and instrument diagrams (P IDs) should be reviewed to confirm the measurement and control components that have a direct impact on the quality-critical parameters and data. This exercise should be carried out by an assessment team made up of user representatives with detailed knowledge of both the computer system application and process, and with responsibility for product quality, system operational use, maintenance, and project implementation. This exercise may be conducted as part of an initial hazard and operability study (HAZOP) and needs to confirm the quality-related critical parameters for use in (or referenced by) the computer control system URS. 

The URS can contain a large number of requirements and should therefore be structured in a way that will permit easy access to information. The requirement specification must be formally reviewed and approved by the pharmaceutical manufacturer. A number of general guidelines apply to this specification (and all validation life-cycle documents). 

From this point in the design and development it is normally the supplier s contracted responsibility to lead the review activities and to provide all documentation and information necessary to undertake each review. To best ensure that the requirements detailed during the definition phase are fully covered by system design and development, the key review sessions should have appropriate representation from the groups primarily involved with the system application and operation and should verify adherence to the supplier s project and quality plan. This involvement will afford the pharmaceutical manufacturer a better understanding of the documentation that details how the supplier is meet-... 

Authority to make inspections, review and copy documents, and take samples and collect other evidence Ability to enforce requirements and to remove products found in violation of such requirements from the market Substansive manufacturing requirements Accountability of the regulatory authority Inventory of current products and manufacturers System for maintaining or accessing inspection reports, samples and other analytical data, and other firm/product information Mechanisms in place to assure appropriate professional standards and avoidance of conflicts of interest Administration of the regulatory authority... 

The Committee was informed that the supplementary guidelines on GMP for the manufacture of herbal medicines had been reviewed and updated over recent years through an extensive consultation process. The Committee adopted the document with minor editorial corrections (Annex 3). 

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