12-Feb-2003

Putting validation

Abstract

Philip van Beek, of DBU Cleanroom Techniek, discusses the difference between commissioning and validation and how to make validation a continuous plan

Validation is not a process which starts following the completion of a facility, it is, or should be, an integral part of the design of the unit. From the very first phase of the process, validation should be taken into consideration.

To be sure of successfully validating a system, it is essential GMP principles are considered: a. Write good procedures. b. Follow those procedures. c. Document the work. d. Design and build proper facilities and equipment. e. Validate manufacturing and testing processes. f. Maintain facilities and equipment. g. Audit for compliance. Once these principles are incorporated into a daily routine, validation becomes a primary consideration. To facilitate this, thought should be given to a validation master plan which would control the procedures of, for example, facilities, utilities, equipment and processes.

Validation elements The first step is to ensure the validation processes are appropriate to the product being manufactured. Validation elements which can be used are: • DQ • Commissioning • IQ • OQ • Modified Qualification • Retrospective PQ • Prospective PQ • No validation Based on the impact the equipment in the system has on the final product, a choice has to be made on which elements are used. One solution is to classify the equipment into: • Direct impact. • Indirect impact. • No impact. This means it must be determined which instruments and equipment require GMP compliance with regard to maintenance, calibration and documentation. Determined by impact on safety, identity, strength, purity and quality, is the equipment critical or non-critical? The bottom line is, does it effect the product or process? Direct impact means it directly influences product quality, while indirect impact means it is not expected to influence quality, but supports a direct impact part of the system. It is important to understand that it is not necessary to maintain all equipment in a validated state. The table shows a general overview of the validation requirements defined by the system's impact on the process.

Commissioning vs validation Both demonstrate conformance to design specifications and user requirements, but there is a crucial difference between them. Commissioning is a business/engineering process in accordance with ISO 9001 and performed according to Good Engineering Practice. It is used for facilities with indirect impact and for qualification attributes not related with direct impact. Validation/Qualification, on the other hand, is a regulatory and quality process and is a final check of equipment, system installation and operation using pre-approved protocols to inspect and test for GMP compliance. It should not be forgotten, however, that some commissioning activities may be used to support qualification. This means the documentation has to be controlled and produced to GMP standards. After commissioning, it must be assured that the system is protected from change. Commissioning is normally used for the documented start-up and turnover of facilities, systems and equipment. It can be simply integrated in the normal validation sequence for systems with indirect impact. This means more transparency, avoiding duplication of work and saving time and money if, of course, the documentation is controlled and according to GMP standards.

Legacy systems Turning to inherited, or "legacy" systems, these are in daily practice difficult to validate. In certain cases a modified qualification sequence can be used by making a combination of the different qualifications. This offers a streamlined approach for indirect legacy systems. Firstly, the critical parameters must be defined using batch records. Drawings must then be checked and confirmed and the system documentation brought up to the required level. Finally, the performance of the system is assessed against the parameters. If this is carefully documented, it is defendable against the authorities and naturally saves both time and cost when compared to conventional methods.

Maintaining a validated state Before starting a revalidation programme, the supporting documentation must be checked, something which is commonly omitted when revalidating. The operational support must include documented instructions for operations, which are necessary to keep the system in a validated state over its full lifecycle. The requirements are: • Vendor manuals • Alarm handling procedures • Cleaning procedures. Important questions include: Is information available to restart the system in case of a catastrophic failure? Are the operators trained to perform the job? And not least, are the levels of security access defined? The ultimate goal in delivering products to the customer lies in consistency. And to assure consistency in the product delivered to your customer, the probability of contamination, mix-ups and errors must be reduced. It must be assured that the products are safe, pure and effective by managing and controlling procedures. Validation and maintaining a validated state is a must.

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