Quality control testing on sterile preparation shall be carried out inhouse andor outsourced. Pharmaceutical microbiological quality assurance and control. Manufacturers cannot afford to overlook key quality, sterile product attributes or parts of their pharmaceutical quality system pqs that identify and mitigate risk. Formulation approaches that discuss a variety of dosage. Applying quality by design to sterile manufacturing processes. Qualified clean room facilities shall be inspected routinely by auditors from the pharmacy practice and development division, ministry of. Justification for the use of aseptic filling for sterile. The packaging process parameters may affect the final product quality. 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.
Addresses the key concepts and applications in sterile product area. 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. Sterile products can be processed by aseptic manufacturing or can be terminally sterilized. As a result we sometimes default to time tested, familiar solutions known to have worked in the past. Pdf intravenous admixture compatibility for sterile. Concepts in sterile preparations and aseptic technique. Design, validation, and control of sterile manufacturing. Sterile product development ekirja ellibs ekirjakauppa. Sterile product packaging systems consist of glass, rubber, and plastic materials that are in intimate contact with the formulation. Fdaapproved labeling product package insert rarely describes environmental quality e. 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.
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. Quality by design qbd of sterile dosage form packaging. Clean areas for the production of sterile products are classified into grades a, b, c and d. Illustrates fundamental understanding as well as practical implications in sterile product development life cycle. During the development of packaging for sterile products, it is important to understand the impact of material attributes and process parameters on cqas. Sep 16, 2010 in the ideal state, the safest product is brought to market initially. 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. This is accomplished primarily by validation of the sterilization process or of the aseptic procedures.
Applicant has indicated that pharmaceutical equivalence data. 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. This limit for contamination is necessary to reduce the risk of product contamination. Significant concerns with the final packaging, manufacturing process, or methods for use were difficult to resolve at that point. 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 drug products produced by aseptic processing current good manufacturing practice guidance for industry september 2004. A pharma product administered parenterally bypasses the bodys natural defense mechanisms. The development of a sterile product requires that specific critical. Finishing of sterile products references further reading.
Sterile pharmaceutical products download ebook pdf, epub. Aug 22, 2012 packaging aspects must be considered during the development of sdfs. Sterile manufacturing has become increasingly more complex because of the increase in the number of poorly stable compounds, new technologies, unit operations, and controls. 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. 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. Provides guidelines for development of policies and procedures for the safe preparation of sterile preparation. Accompanying reconstitution diluents1 should also be included in the development strategy. Note that for lyophilized products, vials of sterile products are stoppered but not fully sealed until the lyophilization process is completed. Annex 6 who good manufacturing practices for sterile. Broad range of indepth information on numerous topics. These products by design are required to be free from living microorganisms, pyrogens and unacceptable particulate matter. Key concepts relevant to the successful development of sterile products are illustrated through case studies and are covered under three sections in this book.
Guidance on the manufacture of sterile pharmaceutical. Sterile drug products produced by aseptic processing. Process design is typically the biggest challenge for a companys process development team and has tremendous impact on the success of the product. 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. In the ideal state, the safest product is brought to market initially. Molecule and manufacturability assessment leading to robust commercial formulation for therapeutic proteins ranjini ramachander, nitin rathore. Microbial ingress must be prevented, while still permitting gasliquid flow ensuring product sterility e. Overview development and manufacturing of injectable. Design of a given area involves satisfying microbiological and particle criteria as defined by the equipment, components, and products exposed, as well as the. Sterile product formulation development is more than just deciding which excipients to use with the given drug substance. Pharmaceutical microbiological quality assurance and.
Parenteral parenteral refers injectable route of administration. Sterile definition of sterile by medical dictionary. These products must be produced in conditions that. Formulation, process, quality and regulatory considerations this comprehensive book encompasses various. Packaging aspects must be considered during the development of sdfs. 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.
Emphasis will be oriented toward formulation development and product manufacture of quality sterile dosage forms that meet or exceed expected good manufacturing practice requirements. Basic requirements for aseptic manufacturing of sterile. Sterile product facility design dme engineering for life sciences. Product and manufacturing process development, as well as safe use and product design, are among the elements of enhanced technical. Sterile product development formulation, process, quality and. Pda presentation sterile product package testing usp 1207. 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 products pharmaceutical development center pdc. Pharmaceutical compounding nonsterile preparations. 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. Sterile product development formulation, process, quality. 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. Identify factors contributing to the development of sterile. These materials can significantly affect the stability of the.
Guidance on the manufacture of sterile pharmaceutical products produced by terminal sterilization. Sterile pharmaceutical products produced by terminal sterilization. The key aspect of the pharmaceutical development process is to design a product and create a manufacturing process that consistently. Formulation, packaging, manufacturing, and quality teaches the basic principles of the development and manufacture of high quality sterile dosage forms. Basic principles of sterile product formulation development martin a. 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. Formulation development studies achieve those optimal conditions through either the use of additives or the manner in which the drug is processed. 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. 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. If a product is prepared for a single patient, end product testing is not needed j. Pharmaceutical compounding sterile preparations established requirements for the aseptic preparation of sterile dosage forms.
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. Chapter formulation development of parenteral products. Key concepts relevant to the successful development of sterile products are. Pharmaceutical sterile products training nsf international. Pdc has sterile fill capabilities for small volume powders to support phase i and phase ii clinical development. So it is a route of administration other than the oral route. Sterility is best achieved through sterile filtration of the bulk using a membrane filter 0. Formulation development an ophthalmic formulation could be a solution, suspension, ointment or an emulsion. Pharmacopeial procedures are not by themselves designed to ensure that a batch of product is sterile or has been sterilized. Clean areas should be ma intained to an appropr iate. We documented that your investigations into these product quality defects were inadequate and failed to spur appropriate corrective actions and preventive actions. The comparator product is a lyophilized powder while the proposed generic product is a ready to use solution. Consequently, any quality defect could potentially cause serious harm to the end user. Under special conditions we have depyrogenated powders at low temperature and under complete vacuum to avoid stability issues with temperature and oxygen sensitive drugs.
1052 1322 773 1231 1502 487 1302 466 1460 1317 40 36 382 879 1003 842 367 1130 651 116 1179 106 887 863 158 1174 31 1086 157 617 903 59 457 1392 898 479 500