This chapter provides a practical approach to computerized system validation (CSV) for the pharmaceutical organizations for the users dealing with the validation. Validation package including plan, responsibilities, and documentation needed and created during the validation are also discussed. Any computer system can be validated utilizing the techniques described here. These activities address the organization commitment to implement the underlying system in order to improve, ensure and maintain the quality standards. The CSV is described as a reference and an orientation guide to understand the related quality processes. The activities presented here should be useful for initiating and conducting the principal tasks of validation. This chapter reflects a quick guide and addresses one of the “non-technical” aspects of CSV methodology. A clear approach is presented that defines the CSV activities and provides an efficient means of validation to new and existing systems, applications, and environments within the organization.
Several definitions are available to define computerized system including European Parliament in the Annex-11 (computerised system) relating to the respect of medicinal products for human use and investigational medicinal products for human use (EC, 2003); the FDA’s definition of computerized system (FDA, 1987a).
Computerized system may include operating environment (Unix, DOS, NT, etc) programming language (Basic, C++, Java, etc), data base (Oracle, Access, DB2, etc), any software, hard disk, processor, network materiel, data input, electronic processing and the output of the information to be used either for reporting or automatic control. It may include automated manufacturing equipment, process control systems, automated laboratory equipment, laboratory data capture system, clinical or manufacturing database systems, etc (Hussain et al. 2006).
Key Terms in this Chapter
Computerized System: A system that includes software, hardware, application software, operating system software, supporting documentation, e.g. automated laboratory systems, control systems, manufacturing, clinical, or compliance monitoring database systems, etc…
Acceptance Testing: Functional acceptance tests of the system performed with the supplier/developer.
GLP: Stands for good laboratory practice embodies an international set of quality regulations and guidelines applicable to the non-clinical studies in the evaluation of drugs, medical devices, biological product, etc… GLP provides a framework within which FDA ensures laboratory studies are planned, performed, monitored, recorded, reported and archived under 21 CFR Part 58.
SLA: Stands for Service Level Agreement and provides the predefined and standard level of services available in the organization and ease the process to establish a solution-specific SLA.
Functional Specification: It defines what the system should do, and what functions and facilities are to be provided. It provides a list of design objectives for the system (GAMP 4).
AFSSAPS: Stands for French Health Products Safety Agency is the French authority for all safety decisions taken concerning health products from their manufacturing to their marketing, i.e.: medicinal products, raw materials for pharmaceutical use, organs, tissues and cells and products of human and animal origins, etc.
Validation Plan: A plan created by the customer to define validation activities, responsibilities and procedures.
cGMP: Stands for current good manufacturing practice is an international set of quality regulations and guidelines applicable to the manufacture, testing and distribution of drugs, medical devices, diagnostic products, biological for human or veterinary use, etc. FDA ensures quality product applicable to GMP via 21 CFR Part 210 and 211 regulations.
GCP: Stands for good clinical practice is an international set of quality regulations and guidelines for design, conduct, monitoring, recording, auditing, analysis, and reporting of studies applicable to the clinical or human studies in the evaluation of drugs, medical devices, biological product, etc… FDA ensures quality product applicable to GCP via 21 CFR Part 50, 54 & 56.
GxP / BPx: GxP / BPx is generalization of any quality guidelines used in the pharmaceutical industry that groups together the following compliance practices, cGMP: Current Good Manufacturing Practice, GLP: Good Laboratory Practice, GCP: Good Clinical Practice.
Supplier: Entity (external company or internal department) that designs and produces the computerized system.
21 CFR Part 11: FDA code of US Federal Regulations, Title 21, Part 11 (21 CFR Part 11) Electronic Records; Electronic Signatures applicable since 1997 that defines parameters by which pharmaceutical companies can author, approve, store, and distribute records electronically.
Operation Qualification (OQ): Documented evidence that, under anticipated conditions, the system or a part of the system operates in accordance with the pre-established functional specifications.
FDA: Stands for Food and Drug Administration, the branch of US federal government which approves new drugs for sale and is responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines, and medical devices, including those used in the diagnosis, treatment, regulation, etc.. for USA.
GAMP: Stands for good automated manufacturing practice is a technical sub-committee of the International Society of Pharmaceutical Engineering (ISPE). Its goal is to encourage and promote a better understanding of the regulation and role of automated systems in the pharmaceutical industry.
Design Qualification (DQ): Documented evidence that the specifications, design, and implementation of the computerized system (hardware and software) are appropriate for their intended use.
Quality Management: Quality management is a continuous process that aims at quality improvement and overall performance in all processes and activities in the organization.
SOP: Stands for Standard Operating Procedure is a written document that describes in details how a particular procedure or method is executed for repetitive use. It is generally intended to standardize the procedure performance.
Code Review: A process to detect possible coding errors, implement path analyses and determine adherence to design specifications and standards by reviewing the source code.
BPF: Stands for “Bonnes Pratiques de Fabrication” in french. It is the equivalent of GMP.
DRP: Stands for disaster recovery plan is the plan for business continuity in the event of a disaster that destroys business resources. The goal of DRP is to recover the technical infrastructure that supports business continuity, in the event of a serious incident in the least possible time.
Change Management (CM): The complete set of processes employed for tracking all changes from existing and new systems, applications, and environments defined by a respective pharmaceutical regulatory conformance and to mange systematically the effects of change.
Performance Qualification (PQ): Verification that, under actual operating conditions, the computerized system operates as expected and that the results (actual data) are as expected.
Vendor Audit: A systematic and independent examination to determine whether quality activities and related results comply with a documented quality system and whether this documented quality system is implemented effectively and is suitable to achieve the contractual requirements placed by the customer.
Installation Qualification (IQ): Documented evidence that the computerized system (hardware and software) is installed in accordance with the requirements of the manufacturer and of the user and that the supplier documentation is in place.
Validation: Documented evidence providing a high degree of assurance that a specific process under consideration does what it purposes to do. Validation deals with the entire system lifecycle to ensure a system satisfies user requirements, meets compliance expectations and adequately maintained to provide a secure environment with accurate, reliable, and traceable information from conception to retirement. The term is also used to describe the overall validation approach including qualification. Validation includes but is not limited to manufacturing processes, equipments, computerized system, etc.