1 Review Article Pharmaceutical Process Validation: An Overview Md. Shoaib Alam* ABSTRACT. Research Scientist, PDL The goal of the CGMPs for the 21st Century initiative such as advancing Formulation, science and technological innovation. Update guidance based on regulatory Ranbaxy Lab Ltd, Paonta Sahib, experience since 1987. Process Validation emphasise on Process design Himachal Pradesh-173025 elements and maintaining Process control during commercialization and communicate that Process validation is an ongoing program and align J. Adv. Pharm. Edu. & Res. Process validation activities with product lifecycle. Process validation also emphasizes the role of objective measures and statistical tools & analyses and emphasizes knowledge, detection, and control of variability and gives assurance on consistent of quality/productivity throughout life cycle of product. Key words: Process Validation, Process Validation Decision Tree, Process Validation Stages, Validation Acceptance Criteria, Deviation INTRODUCTION careful and systemic attention to a number of Pharmaceutical Process Validation is the most importance factors, including: selection of quality important and recognized parameters of CGMPs.
2 Process through in- Process and end-product The requirement of Process validation appears of testing. . the quality system (QS) regulation. The goal of a quality system is to consistently produce REGULATORY REQUIREMENTS FOR. products that are fit for their intended use. Process VALIDATION . Process validation is a key element in assuring FDA regulation describing current good that these principles and goal are met.  The manufacturing practices (CGMPs) for finished Process validation is standardization of the pharmaceuticals are provided in 21 CFR parts validation documents that must be submitted 210 and 211. The CGMP regulations require that with the submission file for marketing manufacturing processes be designed and authorization. The Process validation is controlled to assure that in- Process materials intended to assist manufacturers in and the finished product meet predetermined understanding quality management system quality requirements and do so consistently and (QMS) requirements concerning Process reliably.
3 Process validation is required, in both validation and has general applicability to general and specific terms, by the CGMP. manufacturing Process . According to FDA, regulations in parts 210 and 211. The foundation assurance of product quality is derived from for Process validation is provided in Address for correspondence (a), which states that here shall be written Md. Shoaib Alam procedures for production and Process control Research Scientist, PDL Formulation, Ranbaxy Lab designed to assure that the drug products have Ltd, Paonta Sahib, Himachal Pradesh-173025. Email: the identity, strength, quality, and purity they purport or are represented to possess . The Access this article online CGMP regulations regarding sampling set forth a Journal of Advanced Pharmacy Education & Research Oct-Dec 2012 Vol 2 Issue 4 185. Md. Shoaib Alam, et al.: Pharmaceutical Process Validation: An Overview number of requirements for validation: samples According to US FDA.
4 Must represent the batch under analysis ( In 1978, . (b)(3)); the sampling plan must result in A validation manufacturing Process is one which statistical confidence ( (c) and (d)); and has been proved to do what it purports or is the batch must meet its predetermined represented to do. The proof of validation is specifications ( (a)). The CGPM obtained through the collection and evaluation of regulations also provide norms for establishing data, preferably, beginning from the Process in- Process specifications as an aspect of Process development phase and continuing the validation. Section (b) establishes two production phase. Validation necessarily includes follow when establishing in- Process Process qualification (the qualification of specifications. materials, equipment, system, building, The first principle is that in- Process personnel), but it also includes the control on the specifications for such characteristics [of in- entire Process for repeated batches or runs.]
5 Process material and the drug product] shall be In 1987, (6). consistent with drug product final specifications . Process validation is establishing documented The second principle is this regulation further evidence which provides a high degree of requires that in- Process specifications shall be assurance that a specific Process (such as the derived determined by the application of suitable manufacture of Pharmaceutical dosage forms). statistical procedures were appropriate . The will consistently produce a product meeting its CGMP regulations require that facilities in which predetermined specifications and quality drugs are manufactured be of suitable size, characteristics . construction, and location to facilitate proper In 2008, (6). operations ( ). Equipment must be of Process Validation is defined as the collection appropriate design, adequate size, and suitable and evaluation of data, from the Process design located to facilitate operations for its intended stage throughout production, which establishes use ( ).
6 Automated, mechanical and scientific evidence that a Process is capable of electronic equipment must be calibrated, consistently delivering quality products . inspected, or checked according to the written In 2011, program designed to assure proper performance The revised guidance also provides ( ). recommendations that reflect some of the goals In summary, the CGMP regulations require that of FDA's initiative entities Pharmaceuticals manufacturing processes be designed and CGMPs for the 21st century A Risk-Based controlled to assure that in- Process material and Approach, particularly with regards to the use of finished product meet predetermined quality technological advances in Pharmaceutical requirements and do so consistently and manufacturing, as well as implementation of reliability throughout product lifecycle. modern risk management and quality tools and concepts . Process VALIDATION DEFINITION According to EMEA. 186 Journal of Advanced Pharmacy Education & Research Oct-Dec 2012 Vol 2 Issue 4.
7 Md. Shoaib Alam, et al.: Pharmaceutical Process Validation: An Overview In March 2012, (1) Equipment design features ( material of Process validation can be defined as construction cleanability, etc.). documented evidence that the Process , operated Installation conditions (wiring, utility, within established parameters, can perform functionality, etc.). effectively and reproducibly to produce a medical Calibration, preventative maintenance, product meeting its predetermined specifications cleaning schedules. and quality attributes. Safety features. Continuous Process verification (PCV) has been Supplier documentation, prints, drawings introduced to cover an alternative approach to and manuals. Process validation based on a continuous Software documented. monitoring of manufacturing performance. This Spare parts list. approach is based on the knowledge from Environmental conditions (such as clean product and Process development studies and / room requirements, temperature, and or previous manufacturing experience.)
8 CPV may humidity). be applicable to both a traditional and enhanced Operational Qualification (OQ): Establishing by approach to Pharmaceutical development. It may objective evidence Process control limits and use extensive in-line, on-line or at-line action levels which result in product that all monitoring and / or controls to evaluate Process predetermined requirements. performance. (7) Process validation should OQ considerations include: confirm that the control strategy is sufficient to Process control limits (time, temperature, support the Process design and quality of the pressure, line speed, setup conditions, etc.). product. The validation should cover all Software parameters. manufactured strengths and all manufacturing Raw material specifications sites used for production of the marketed Process operating procedures. product. (7). Material handling requirements. Process change control. BASIC PRNCIPLE FOR Process . Training. VALIDATION (1, 3, 8, 12, 13).
9 Short term stability and capability of the The basic principle for validation may be stated Process , (latitude studies or control charts). as follows: Potential failure modes, action levels and Installation Qualification (IQ): establishing by worst-case conditions. objective evidence that all key aspects of the The use of statistically valid techniques such Process equipment and ancillary system as screening experiments to optimize the installation adhere to the manufacturer's Process can be used during this phase. approved specification and that the Performance Qualification (PQ): establishing recommendation of the supplier of the by objective evidence that the Process , under equipment are suitably considered. anticipated conditions, consistently produces a IQ considerations are: Journal of Advanced Pharmacy Education & Research Oct-Dec 2012 Vol 2 Issue 4 187. Md. Shoaib Alam, et al.: Pharmaceutical Process Validation: An Overview product which meets all predetermined Process VALIDATION WITHIN THE.
10 Requirements. QUALITY MANAGEMENT SYSTEM (3). PQ considerations include: Process validation is part of the integrated Actual product and Process parameters and requirements of a quality management system. It procedures established in OQ. is conducted in the context of a system including Acceptability of the product. design and development control, quality Assurance of Process capability as assurance, Process control, and corrective and established in OQ. preventive action. The product should be design Process repeatability, long term Process robustly enough to withstand variations in the stability. manufacturing Process and the manufacturing Re Qualification: Modification to, or relocation Process should be capable and stable to assure of equipment should follow satisfactory review continued safe products that perform adequately. and authorization of the documented change Corrective actions often identify inadequate proposal through the change control procedure.