A Proposed Standard for the Documentation Used to Support Validation, Part 1
Editor's Note: This paper is excerpted from a presentation to be delivered at the InterPhex Show in Philadelphia during the week of March 15, 1998
By the Jett Consortium. Members:
Dale Noteboom, Pharmacia & Upjohn
James Brooke, Eli Lilly & Company
Michael Quane, Abbott Laboratories
James John, Allen-Bradley Company
Mitch Cook, Paul Mueller Company
Russell Lindsey, Paul Mueller Company
Introduction
This paper describes a proposed standard for documentation used to support validation of newly acquired, single-purpose, "packaged" or "skid-mounted" equipment or systems such as:
It also describes the responsibilities of the Customer (a pharmaceutical manufacturer [User] or its agent) and the Supplier (an equipment manufacturer or vendor) when producing those documents. We describe the JETT Consortium's methodology, a methodology which is based on the GAMP ("Good Automated Manufacturing Practices") methodology.
The JETT Consortium, originally known as the Joint Equipment Transition Team, was formed on 31 July, 1996 in response to a perceived need to standardize documentation requirements for packaged equipment. The original members included representatives from Abbott Laboratories, Eli Lilly & Company, Pharmacia & Upjohn, and Rockwell Automation (Allen-Bradley). The following issues were identified:
- Reduced internal resources have made it necessary for many Users to rely more heavily on the Suppliers for documentation which supports and aids validation.
- Reduced internal resources have made it necessary for many Users to purchase more "standard" systems and fewer "custom" systems.
- There is common frustration among many Users with the Supplier-provided "validation" documentation and, sometimes, the substantial upcharge which accompanied it.
These issues were discussed at length, and it was decided that the key objective of the Consortium would be to improve the documentation deliverables and the procedures which relate to validation (if necessary) of the Suppliers who provide "packaged" equipment.
Improved Customer/Supplier relationships will not come easily or quickly. There is frustration "on both sides of the table," so to speak. Customers are frustrated with Suppliers' lack of "proper" documentation and inadequate or poorly documented validation-related procedures. Many Customers believe that a documentation package such as this one proposed by the Consortium should not result in a substantial "up-charge" or "adder cost." They want documented evidence of the "built-in quality" that the Suppliers claim to provide, and they believe that this evidence should be included as "standard."
Suppliers, on the other hand, are frustrated with Customers' lack of clarity and precision in specifying equipment, procedure, and documentation requirements. Furthermore, these requirements, even when clearly and precisely communicated, are not consistent from Customer to Customer, even when the equipment is identical and intended for the same purpose. Therefore, the Supplier is required to create a "custom" documentation package for each Customer (even if the equipment is "standard"), resulting in a substantial cost to the Supplier which, of course, is passed on to the Customer. This problem is compounded when the Customer requires the Supplier to use a Customer-provided format.
Another issue is that many Customers are attempting to put more of the responsibility for validation documentation onto the Suppliers. There are two reasons for this. The first, which is more obvious but somewhat less important, is that all companies, pharmaceutical or otherwise, are reducing costs in an effort to be more profitable. Some of these cost reductions result in fewer resources for the validation of new equipment. Obviously, if the Customer can persuade the Supplier to make the Customer's validation process easier, faster, or require fewer personnel to complete, the resources required can be reduced.
The second, and more important, reason that Customers are trying to shift the responsibility for validation documentation onto Suppliers is that it is much easier to document the design and construction of new equipment while it is being designed and built than it is after delivery. Furthermore, this documentation, when developed by the Supplier during design and construction, is much more reliable. As a rule, the Supplier is more of an authority on its own equipment than the Customer's validation personnel are likely to be. Also, as a general rule, validation personnel are not "on hand" during design and construction.
How to Improve the Situation
The JETT Consortium recognized that in order to improve this situation, a common, standardized methodology would have to be developed and adopted. It was hoped that a documentation standard could be developed in which, irrespective of the type of system to which the documentation refers, the documentation would use the same or similar formats and place similar types of data in the same or nearly the same locations within the documents, if at all possible.
The GAMP methodology (Good Automated Manufacturing Practices) appeared to be a good pattern on which to develop a standardized methodology for the production of Supplier-provided validation documentation for packaged equipment. The GAMP methodology is gaining wide acceptance in Europe and variations on it are gaining some acceptance in the U.S. Further study provided evidence that the GAMP methodology was reasonably thorough and applied fairly well (for the most part) to packaged equipment. Most importantly, both the Customer's and the Supplier's responsibilities are well defined under the GAMP methodology. For these reasons, the JETT Consortium elected to use the GAMP methodology as the pattern for a proposed standard for Supplier-provided validation documentation used in the U.S.
Introduction to GAMP
The GAMP methodology was developed by the U.K. Pharmaceutical Industry Computer Validation Forum (the Forum) in conjunction with the Association of the British Pharmaceutical Industry (APB) and the Pharmaceutical Quality Group (PQG) of the Institute of Quality Assurance (IQA). It was developed to establish guidelines for Suppliers of automated systems to the pharmaceutical manufacturing industry. These guidelines refer, primarily, to the development of validation documentation but they also refer to the quality management systems which make those documents meaningful and reliable.
The GAMP methodology was developed initially for European Suppliers, but it takes into account the requirements of both the European and North American regulatory bodies. Furthermore, it makes use of existing internationally recognized standards where appropriate.
According to the GAMP Supplier Guide,
- In 1990, the validation of automated systems in pharmaceutical manufacturing assumed a much greater importance than had previously been the case.
Although regulatory guidelines concerning the use of such automated systems had been available for some time, these systems had been subjected to less regulatory scrutiny than some other areas, and the interpretation of the regulatory guidance was less mature than in more conventional areas.
The GAMP methodology is intended primarily for use by Suppliers to the pharmaceutical industry when developing software for automated systems, specifically, for "stand-alone" computer systems. The GAMP methodology can be applied to the design and development, construction, and testing of an automated system.
The JETT methodology is intended for use by both Customers and Suppliers of automated "packaged" or "skid-mounted" sterile production/processing equipment. Most or all of the design and development of this type of equipment has been accomplished and does not change significantly from one system to the next (assuming the same model and manufacturer). Therefore, the JETT methodology has greater impact on the construction and testing of packaged equipment than on design and development.
Overview of Validation
Validation is defined as "establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes."
- Validation is applied to many aspects of pharmaceutical manufacture; examples include services, equipment, computers, processes, and cleaning.
For a new facility, validation will occur in a prospective manner involving both the Customer and the Supplier and will follow a fairly sequential progression as items are handed over to the startup team from the main contractor. For example, buildings and main services may be completed first, followed by equipment and computer systems, then processes and cleaning. (See Note below)
Figure 1 shows the general philosophy of validation with a logical progression from specification through design, preparation of written test plans, performance tests, review of results, and ongoing operation. Supplier Guide.
Figure 1
Go to A Proposed Standard for the Documentation Used to Support Validation, Part 2
Note: Guide, Section 7, "Overview of Validation."
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