Pharmaceutical manufacture documentation

Figure 11.9 Examples of documentation associated with pharmaceutical manufacture.

Pharmaceutical Manufacturers Association (PMA). (1988). Results of a Questionnaire Involving the Design of and Experience with Carcinogenicity Studies. This document has not been published in the open literature but is widely available within the pharmaceutical industry. It may be obtained by writing to the Pharmaceutical Manufacturers Association, Washington, DC. 

This previous definition had been broadened after the FDA s issue of the PAT guidance document to encompass aU factors influencing the quality and efficiency of a chemical or pharmaceutical manufacturing process. Driven by developments in Six-Sigma and operational excellence programs an extended definition included such items as ... 

Adequate documentation forms an essential part of good manufacturing practice. For this reason, every aspect of pharmaceutical manufacture is characterized by the existence of extensive associated documentation. This is essential in order to ... 

Most documents associated with pharmaceutical manufacturing fall into one of four categories ... 

As we have already documented, a major market failure is the absence of incentives to develop some drugs that potentially have important social benefits, but that are not currently being developed, in large part because pharmaceutical manufacturers lack an adequate incentive to engage in R D to develop such socially beneficial products. Several types of vaccines are a case in point. Clearly the patent system has proven to be inadequate in providing a sufficient incentive. Perhaps other incentive plans can either replace or supplement existing incentives to correct this market failure. 

This book was designed and written for validation professionals responsible for writing and maintaining quality management systems for the successful operation of their companies. It provides a set of SOPs that can be used to manage and document critical validation and revalidation tasks in a pharmaceutical manufacturing facility. 

An example of a robust process is the design, development, and operation of a nonconformance process. Regulations require an operational process to identify, document, and correct nonconformances occurring in licensed pharmaceutical manufacturing facilities for approved products. Companies spend significant human... 

Discussions with training managers at pharmaceutical manufacturing companies audited by the FDA suggest that it is through documentation/recordkeeping that the FDA backs into an audit of a company s training. This typically happens in one of three ways ... 

Rules and Guidance for Pharmaceutical Manufacturers and Distributors, part 4, Guide to Good Manufacturing Practice for Medical Products, Chapter 6.7, Documentation, 1997. 

Although it is the responsibility of an excipient user to qualify their excipient suppliers, that burden is shared with the distributor as well. A pharmaceutical distributor must provide the user with the assurance that the excipients supplied are unadulterated, have not been tampered with, and are free from contamination. To ensure this, a distributor must have warehouse and internal controls in place, comply with current regulatory standards, and should be an active NACD member. Trace-ability of ingredients is another critical need that must be met by pharmaceutical distributors. This can be achieved by providing the manufacturer s original packaging, documentation, and manufacturing site address, confirmed by the manufacturer. 

In the United States a comprehensive document has been pubhshed by the EPA [25] outlining Best Available Treatment options and the regulatory treatment of effluents arising from pharmaceutical manufacture. However, the most comprehensive control system is currently that provided in the EU by the Directive on Integrated Pollution Prevention and Control [26], and this is becoming a model for the development of similar legislation across the world. 

US Environmental protection Agency (1998). Development Document for Pinal Effluent Limitations Guidelines and Standards for the Pharmaceutical Manufacturing Point Source Category, EPA-821-R-98-005. 

To summarize, the VMP or QMP should be a brief overview of the project, tasks, tools, resources, and methods that are going to be used during the project. This document should be described at a very early stage of a project by the engineering or manufacturing department of a pharmaceutical manufacturer or service provider. 

User requirement specifications cover more aspects than only the GMP requirement, because the URS is not written only for the validation procedure in fact, a URS is a very important project document covering technical as well as economic requirements of the technical system. Pharmaceutical manufacturing departments not only check the GMP aspects of a system additionally, following good engineering practice they will review the technical and economic aspects of a technical system. Obviously, the more experience a company gains, the more comprehensive a URS become. Past experiences such as project faults, inefficient technical systems, and bad commissioning can be included in a URS. 

Does the system provide adequate documentation of the application With this in mind and to achieve and maintain validated computer systems, pharmaceutical manufacturers need to include the following as part of their compliance policy ... 

The pharmaceutical manufacturer must establish effective policies and plans for regulatory compliance and validation to enable individuals to clearly understand the company commitment and requirements. Computer validation planning should ensure an appropriate training program, preparation of validation guidelines and procedures, system GMP compliance risk and criticality assessment, a documented validation strategy and rationale, clearly defined quality-related critical parameters and data for the manufacturing process. 

The pharmaceutical manufacturer must ensure that personnel are trained to an appropriate level in GMP and validation planning and requirements to enable them to adequately perform their function. This applies to any resource used in connection with GMP compliance and validation life-cycle activities and documentation. A training program should be in place and individual training records maintained. The records and suitability of external resources used by suppliers or contractors should also be examined. 

As with all validation life-cycle documents, a validation plan is a formal document produced by the pharmaceutical manufacturer. The plan should require that all validation documentation is under a strict document control procedure, with issue and revision of documents controlled by means of an approval table, identifying the name, signature, date, and level of authority of the signatory. 

The overall project itself requires formally structured planning and control in addition to the validation plans for the computerized operation. To provide this, a project and quality plan from the pharmaceutical manufacturer (or its nominated main contractor) is normally developed as a separate and complimentary document and needs to overview all activities, resources, standards, and procedures required for the project. The plan should define project-execution procedures, quality management procedures, engineering standards, project program, and project organization (with authorities and reporting responsibilities), and reference the project validation plan. There are instances in which the project and quality plan and the project validation plan can be combined into one document. 

As part of the supply contract each supplier or subcontractor needs to provide a corresponding project and quality plan to identify and outline the procedures, standards, organization, and resources to be used to align with the requirements of the pharmaceutical manufacturer s project. The contractors and suppliers involved with GMP work should reference the project validation plan and identify the specific requirements that are to be addressed to ensure the appropriate level of documentation in support of the pharmaceutical manufacturer s validation program. 

Project and quality planning by each company is important for multigroup projects, as it enables all those involved in the project—pharmaceutical manufacturer, vendor, or third party—to access a formal definition of project standards, schedule, organization, and contracted responsibilities and monitor interaction at all levels. If elements of the contracted work and supply are to be subcontracted the plan must detail how this work is to be controlled and reported. The supplier project and quality plan must be a contractual document agreed upon by the purchaser and supplier and needs to ensure that ... 

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). 

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