Applying quality by design to sterile manufacturing processes. Basic requirements for aseptic manufacturing of sterile. The development of a sterile product requires that specific critical. A typical eye care product is sterile, nearly isotonic, has some buffering capacity, contains antimicrobial agents unless the active itself is bacteriostatic and is packaged into a suitable tamperevident, multidose dispensing system. Clean areas should be ma intained to an appropr iate. These products must be produced in conditions that. Pdc has sterile fill capabilities for small volume powders to support phase i and phase ii clinical development. In addition, however, the temperature, humidity and air pressure of the environment should be regulated to suit the clean room processes and the comfort of the operators.
Sterile product packaging systems consist of glass, rubber, and plastic materials that are in intimate contact with the formulation. The initial risk assessment of cqas and cpps of a generic company should be based on desk research and own experience with the manufacture of the dosage form an example is illustrated in annex 2. Pharmacopeial procedures are not by themselves designed to ensure that a batch of product is sterile or has been sterilized. Justification for the use of aseptic filling for sterile.
Applicant has indicated that pharmaceutical equivalence data. Sterility is best achieved through sterile filtration of the bulk using a membrane filter 0. Sep 16, 2010 in the ideal state, the safest product is brought to market initially. Additionally, since the bodys natural defenses are bypassed when injecting this type of drug product, special care must be taken to ensure that microorganisms and other. Parenteral parenteral refers injectable route of administration. Annex 6 who good manufacturing practices for sterile. Sterile pharmaceutical products download ebook pdf, epub. Chapter formulation development of parenteral products. Clean areas for the production of sterile products are classified into grades a, b, c and d.
Equipment surfaces that contact sterilized drug product or its sterilized containers or closures must be sterile so as not to alter purity of the drug 211. Introduction to sterile product preparation this activity discusses the guidelines, best practices, standards, and regulations that influence and contribute to safe sterile product preparation practices. A pharma product administered parenterally bypasses the bodys natural defense mechanisms. Pda presentation sterile product package testing usp 1207. Emphasis will be oriented toward formulation development and product manufacture of quality sterile dosage forms that meet or exceed expected good manufacturing practice requirements. The packaging process parameters may affect the final product quality. Process design is typically the biggest challenge for a companys process development team and has tremendous impact on the success of the product. In the ideal state, the safest product is brought to market initially.
Sterile manufacturing has become increasingly more complex because of the increase in the number of poorly stable compounds, new technologies, unit operations, and controls. Formulation, packaging, manufacturing, and quality teaches the basic principles of the development and manufacture of high quality sterile dosage forms. Accompanying reconstitution diluents1 should also be included in the development strategy. Design, validation, and control of sterile manufacturing. Qualified clean room facilities shall be inspected routinely by auditors from the pharmacy practice and development division, ministry of. Sterile product development ekirja ellibs ekirjakauppa. Sterile product facility design dme engineering for life sciences. Pharmaceutical microbiological quality assurance and control. Dec 09, 20 equipment surfaces that contact sterilized drug product or its sterilized containers or closures must be sterile so as not to alter purity of the drug 211. Sterile product formulation development is more than just deciding which excipients to use with the given drug substance. Sterile drug products produced by aseptic processing.
This is accomplished primarily by validation of the sterilization process or of the aseptic procedures. Product and manufacturing process development, as well as safe use and product design, are among the elements of enhanced technical. Key concepts relevant to the successful development of sterile products are illustrated through case studies and are covered under three sections in this book. Render free of viable organisms surfaces that are in the vicinity of the sterile product validate the processes used to sterilize critical equipment, containers and closures. Concepts in sterile preparations and aseptic technique. This book is a useful resource to scientists and researchers in both industry and academia, and it gives process and product development engineers insight into current industry practices and evolving regulatory expectations for sterile product development. Sterile products can be processed by aseptic manufacturing or can be terminally sterilized. Pdf intravenous admixture compatibility for sterile. Under special conditions we have depyrogenated powders at low temperature and under complete vacuum to avoid stability issues with temperature and oxygen sensitive drugs. If a product is prepared for a single patient, end product testing is not needed j.
Finishing of sterile products references further reading. Formulation approaches that discuss a variety of dosage. So it is a route of administration other than the oral route. Drug product, container, and closure are first subjected to sterilisation methods separately and appropriately. Overview development and manufacturing of injectable. Guidance on the manufacture of sterile pharmaceutical products produced by terminal sterilization. Manufacturers cannot afford to overlook key quality, sterile product attributes or parts of their pharmaceutical quality system pqs that identify and mitigate risk. Chapman study points the requirements for sterile production grades of clean areas design and operation of clean areas isolators environmental monitoring preparation of aseptic products introduction the production of sterile medicinal products has special requirements. Sterile pharmaceutical products produced by terminal sterilization. Broad range of indepth information on numerous topics. Consequently, any quality defect could potentially cause serious harm to the end user.
Design of a given area involves satisfying microbiological and particle criteria as defined by the equipment, components, and products exposed, as well as the. Significant concerns with the final packaging, manufacturing process, or methods for use were difficult to resolve at that point. Formulation development studies achieve those optimal conditions through either the use of additives or the manner in which the drug is processed. Microbial ingress must be prevented, while still permitting gasliquid flow ensuring product sterility e. The key aspect of the pharmaceutical development process is to design a product and create a manufacturing process that consistently.
Guidance on the manufacture of sterile pharmaceutical. Basic principles of sterile product formulation development martin a. The comparator product is a lyophilized powder while the proposed generic product is a ready to use solution. Quality by design qbd of sterile dosage form packaging introduction the international conference on harmonization ich recently published the q8 r2 guideline for pharmaceutical development 1. Sterile drug products produced by aseptic processing current good manufacturing practice guidance for industry september 2004.
Headspace gas or pressure must be preserved ensuring product stability and sterility 3. Presented at the pda europe parenteral packaging conference brussels, belgium 11 march 2014. Healthcare engineering, product and project managers benefits of attending professionals charged with designing the proper sterile barrier system sbs for medical devices often are under time constraints and stringent budgets. This comprehensive book encompasses various facets of sterile product development. Gmp for sterile pharmaceutical manufacturing ankur choudhary print question forum no comments maintenance of sterile area is a critical task because of air, as well as the personnel working in the sterile classified area, are the main source of the contamination. Pharmaceutical compounding nonsterile preparations. This limit for contamination is necessary to reduce the risk of product contamination. Sterile product development formulation, process, quality and. Aug 22, 2012 packaging aspects must be considered during the development of sdfs. Key concepts relevant to the successful development of sterile products are.
Note that for lyophilized products, vials of sterile products are stoppered but not fully sealed until the lyophilization process is completed. Illustrates fundamental understanding as well as practical implications in sterile product development life cycle. As a result we sometimes default to time tested, familiar solutions known to have worked in the past. Pharmaceutical sterile products training nsf international.
During the development of packaging for sterile products, it is important to understand the impact of material attributes and process parameters on cqas. A method of producing a sterile product in which sterile bulk drug or sterile raw materials are compounded and assembled with sterile packaging components in a controlled environment, in which the entry or supply of air, materials, equipment, and personnel are. Formulation, process, quality and regulatory considerations this comprehensive book encompasses various. Formulation development an ophthalmic formulation could be a solution, suspension, ointment or an emulsion. Sterile products pharmaceutical development center pdc. Provides guidelines for development of policies and procedures for the safe preparation of sterile preparation.
Quality by design qbd of sterile dosage form packaging. These materials can significantly affect the stability of the. Beginning with a brief historical development of parenteral products and parenteral therapy including sterile product characteristics and the importance of sterility, components and packing, it then addresses canadas regulatory environment and professional requirements, guidelines governing the preparation of sterile products, the importance. Particular attention should be paid to the validation2 of analytical test methods so that the laboratory and pilotscale product and process development experiments identify the. In another warning letter, the fda depicts 1,500 complaints from 2012 to 2016 related to leaking, underfilled or empty bottles of a sterile solution. Molecule and manufacturability assessment leading to robust commercial formulation for therapeutic proteins ranjini ramachander, nitin rathore. Quality control testing on sterile preparation shall be carried out inhouse andor outsourced. These products by design are required to be free from living microorganisms, pyrogens and unacceptable particulate matter. Pharmaceutical microbiological quality assurance and. Fdaapproved labeling product package insert rarely describes environmental quality e. Identify factors contributing to the development of sterile. Pharmaceutical compounding sterile preparations established requirements for the aseptic preparation of sterile dosage forms. Concepts in sterile preparations and aseptic technique is an independent publication and has not been authorized, sponsored, or otherwise approved by the owners of the trademarks or service marks referenced in this product.
Addresses the key concepts and applications in sterile product area. With the support of a grant for research on regulatory science of pharmaceuticals and medical devices from ministry of health, labour and welfare of japan. Sterile definition of sterile by medical dictionary. Sterile product development formulation, process, quality. Packaging aspects must be considered during the development of sdfs. We documented that your investigations into these product quality defects were inadequate and failed to spur appropriate corrective actions and preventive actions.
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