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Validation of Aseptic Pharmaceutical Processes: A Comprehensive Review of Current Standards and Reco



Ms. Thomas has over two decades of cGMP hands-on industry experience in both pharmaceutical and medical device manufacturing operations. Her experience covers all Quality Systems; as well as, all areas of validation; including, process/product validation, facilities validation, CSV and 21 CFR Part 11, test method validation, equipment/automated processes and cleaning validation.


To properly complete process validation, manufacturers must carry out and document all three stages of IQ, OQ, and PQ on the equipment they will use to manufacture their devices. The three stages all validate different aspects of the equipment and its associated processes:




Validation of Aseptic Pharmaceutical Processes free download



The current trend is for the aseptic preparation of sterilised drugs to be carried out in hospital pharmacies.(1,2) Many hospitals are gradually abandoning their sterilised production line for a redeployment of resources in aseptic manufacturing (see Figure 1). There is a need for individualised ready-to-use injectables, such as paediatric parenteral nutrition, antibiotics, cytostatic drugs or intensive care pharmaceuticals,(3,4) and many hospital pharmacies have developed their aseptic production units considerably to improve the safety of injectable drugs, thus offering better quality assurance compared with preparations in wards.(5)


Documented procedures and protocolsA structured and comprehensive documentation, including written and approved SOPs for all the critical processes, especially aseptic preparation, is needed. Simple and understandable procedures must be edited for routine operations such as gowning of the operators in the cleanroom. Different qualifications and validations have to be performed on the basis of written protocols, and all the results have to be fully documented. It is important to transcribe every step of every preparation to standardise daily manipulations as much as possible. To summarise, every operation has to be written, approved and traceable at any time.


Quality control of the production environment and equipmentFor aseptic production, the principal equipment is the cleanroom and the laminar airflow hoods (or isolators) installed inside. Initial qualifications of the cleanroom design and filtration system are mandatory. The cleaning and sanitisation of the controlled environment and the validation of its efficiency have become major GMP topics. Routine monitoring of viable and nonviable particle contamination is a necessary task of the quality control laboratory. In addition, microbiological in-process controls, such as settle plates and glove fingerprints, ensure the sterility of the preparation background atmosphere. Discussing monitoring results with operators is of great value, as it involves them in the improvement of the cleanroom quality control.


  • Describes the methodologies and best practices of the sterile manufacture of drug products Thoroughly trained personnel and carefully designed, operated, and maintained facilities and equipment are vital for the sterile manufacture of medicinal products using aseptic processing. Professionals in pharmaceutical and biopharmaceutical manufacturing facilities must have a clear understanding of current good manufacturing practice (cGMP) and preapproval inspection (PAI) requirements. Sterile Processing of Pharmaceutical Products: Engineering Practice, Validation, and Compliance in Regulated Environments provides up-to-date coverage of aseptic processing techniques and sterilization methods. Written by a recognized expert with more than 20 years of industry experience in aseptic manufacturing, this practical resource illustrates a comprehensive approach to sterile manufacturing engineering that can achieve drug manufacturing objectives and goals. Topics include sanitary piping and equipment, cleaning and manufacturing process validation, computerized automated systems, personal protective equipment (PPE), clean-in-place (CIP) systems, barriers and isolators, and guidelines for statistical procedure. Offering authoritative guidance on the key aspects of sterile manufacturing engineering, this volume: Covers fundamentals of aseptic techniques, quality by design, risk assessment and management, and operational requirements

  • Addresses various regulations and guidelines instituted by the FDA, ISPE, EMA, MHRA, and ICH

  • Provides techniques for systematic process optimization and good manufacturing practice

  • Emphasizes the importance of attention to detail in process development and validation

  • Features real-world examples highlighting different aspects of drug manufacturing

Sterile Processing of Pharmaceutical Products: Engineering Practice, Validation, and Compliance in Regulated Environments is an indispensable reference and guide for all chemists, chemical engineers, pharmaceutical professionals and engineers, and other professionals working in pharmaceutical sciences and manufacturing. About the Author Sam A. Hout, PhD, MBA, is a Chartered Chemical Engineer, certified in business management by the American Production and Inventory Control Society (APICS), and a member of the International Society of Pharmaceutical Engineers (ISPE). Dr. Hout held the position of Senior Director of Engineering, project management, and technology process transfers at Siegfried Pharmaceuticals. Previously, he was Senior Manager of Engineering at TEVA Pharmaceuticals and Director of Operations at the HPLC company Phenomenex. Permissions Request permission to reuse content from this site


The EU GMP Annex 1 Revision: Manufacture of Sterile Medicinal Products, updated in 2020, outlines a need for cleaning processes to be validated to remove any residue that could impact effectiveness, as well as minimise the risk of cross-contamination. For manual cleaning procedures, validation requires that strict cleaning procedures are followed and that the environment is monitored before and after disinfection.


In general, process validation remains the responsibility of the biopharmaceutical manufacturer. Supplier data should be appropriately used. Leveraging supplier data requires the end user to understand how the supplier data were developed and assess their suitability to the processes.


A validation master plan (VMP) outlines the principles involved in the qualification of a facility, defining the areas and systems to be validated, and provides a written program for achieving and maintaining a qualified facility. Master plans are written to assist an organization with validation strategies or to provide control over a specific process. The VMP is different from a validation procedure (SOP), which describes the specific process for performing validation activities. The VMP is beneficial for planning purposes because it identifies anticipated resource needs and provides key input into scheduling of project timelines. It documents the scope of the validation effort including impacted product, processes, procedures, facilities, equipment, and utilities.


The validation approach defines the purpose of the VMP in demonstrating the critical equipment, systems, and processes perform as designed and intended. The approach assures all validations will be conducted prospectively following written and approved protocols. It addresses change control and qualification of equipment and systems and ensures they will be conducted in a manner consistent with policies and procedures. The approach states that specific equipment, systems, and processes to be validated will be determined based on a documented risk assessment.


Joy McElroy is the founder and principal consultant at Maynard Consulting Company, which provides services in validation engineering, process engineering, quality control, and quality assurance. McElroy began her career in the pharmaceutical industry performing environmental monitoring and sterility testing, and then moved into a supervisory role overseeing quality control. From there, she moved into QA, and then into equipment qualification and process validation. In addition to consulting, she develops and delivers webinars, on-site training, and seminars in areas such as technical writing, equipment qualification, cleaning validation, FDA audit preparation, and more. You can reach her at joy@maynardconsultingcompany.com or connect with her on LinkedIn. 2ff7e9595c


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