Center for drug evaluation and research, guidance for industry. This information would be included in the filing as part of the process justification. The scaleup process and the changes made after approval in the composition, manufacturing process, manufacturing equipment, and change of site have become known as scaleup and post approval changes, or supac. Change in manufacturing process of the drug substance. Some changes in the scale of manufacture may also be classified in this category. Pharmaceutical process scale up, edited by michael levin 119. Fda releases supac guidance pharmaceutical technology. In simple terms, the process of increasing batch size is termed as scale up. Solid oral dosage forms scaleup and postapproval changes. Scaleup studies in pharmaceutical products development.
This guidance provides recommendations on new drug applications or abbreviated new drug applications on the levels of post approval changes, recommended tests and documentations for cmc changes. This revised draft document combines and supersedes. Comparability assessment and protocols as enablers of change. Pilot scale pilot scale is a first view into continuous processing of a product 3. Scaleup chemical engineering in chemical engineering, the migration of a process from the labscale to the pilot plantscale or commercial scale.
Scaleup, a type classroom layout and learning environment. Mcconville very well presented, gave me a glimpse into the complexity of chemical engineering and how much is possible when transferring. Best practices for the development, scale up, and postapproval. Chemistry, manufacturing and controls, in vitro dissolution testing, and in vivo bioequivalence. Supac guidelines pdf this guidance has been prepared by the immediate release scaleup and post. Bench or laboratory scalethis is an earlystage tools to assess and scaling new product or technology 2. Supacir questions and answers about supacir guidance fda. Bench or laboratory scale this is an earlystage tools to assess and scaling new product or technology 2. Secrets of batch process scaleup ensuring effective translation of laboratory processes to pilot plant scale 24 october 2018 stockholm, sweden elite palace hotel a 3 day course given by francis x. Pqri post approval changes for sterile products working. Chemistry, manufacturing and controls cmc changes are inevitable due to many reasons including changing needs, new findings and continuous improvement. Changes seen after a marketing approval of a medicinal product change in the genetic construct of the cell line andor change in the cell line change in the fermentation process. Post approval change reporting requirements to regulatory authorities, ema and fda.
Fda recommendations for comparability studies to support. Major changes require approval by regulatory authorities before they can be. Try to mimic plant conditions in lab to anticipate effects when scale up. Best practices for the development, scaleup, and postapproval. For applications that make use of the design space concepts, post approval changes may be modified from the descriptions in the documents below, and will be specified and agreed to as part of the application approval process. D is the diameter of the impeller z is the height of the liquid in the vessel and t is the diameter of the tank. The size of the batches is gradually increased scale up. Looking for clarification on reporting postapproval. This webinar is intended for formulators, process engineers, validation specialists and quality assurance personnel, as well as production managers occupied with process and product scaleup and changes in any fda approved production. Since then a number of questions have arisen in interpreting the guidance as it applies to specific situations encountered or that could be encountered in the pharmaceutical industry. Post approval changes in the size of a batch from the pivotalpilot scale biobatch material to larger or smaller production. Fda has released a draft guidance of scaleup and postapproval changes that combines and supersedes previous guidance documents. In addition, drug development must establish the physicochemical properties of the nce.
Problems associated with scaleup might require changes in postapproval that would affect the final formulation composition, site change, and manufacturing process or equipment changes strovel et al. The final guidance encourages drugmakers to use a riskedbased approach in evaluating equipment changes during the scale up and post approval change supac process. Guidance for industry on scaleup postapproval changes. On november 30, 1995, the scaleup and postapproval changes guidance for immediate release products supacir was published.
Comparability assessment and protocols as enablers of. The scale up process and the changes made after approval in the composition, manufacturing process, manufacturing equipment, and change of site have become known as scale up and post approval changes, or supac. Therefore, regulations require that all changes be evaluated carefully and follow the proper. This changes includes process changes like mixing times and operating speed. Introduction to scaleup and postapproval changes supac. Regulation of post approval changes or change control, is one of the most important key elements of regulation of vaccines by the national regulatory authorities. The sizes of the batch is gradually increased scale up. Chemistry, manufacturing and controls, in vitro dissolution testing, and in vivo bioequivalence documentation. All process validation data for process b 10,000l scale trending of all historical data both process a and b clearly labeled including release, characterization, stability data, and an evaluation of process comparability for upstream and downstream process parameters provide evidence that the assay you currently have in place to. Part ii post approval change reporting requirements to. Q11 development and manufacture of drug substances 2012 barely touches on postapproval changes and the guidance for industry. One easy method of developing such estimates is to base them on a known cost.
In vitro release testing and in vivo bioequivalence documentation guidance. Draft guidance for industry on scaleup and postapproval. In the process of developing the new product, the batch size used in earliest human studies are small. Example of manufacturing scale process extract from batch log sheet for crystallisation 1.
Secrets of batch process scaleup scientific update. Chemistry, manufacturing and controls, in vitro dissolution testing, and in vivo bioequivalence documentation supacir, which published in november 1995, and guidance for industry. Immediate release and modified release solid oral dosage forms, manufacturing equipment addendum, and 2 supacss nonsterile semisolid dosage forms, manufacturing equipment addendum. In the united states of america the scale up and post approval changes guidance provides information on various aspects of post approval changes. If change does not alter the stability of the drug product, the previously approved expiration dating period can be used. But now supacir, mr, ss guidance are followed for stability studies.
Controls coordinating committee cmc cc of the center for drug evaluation and. Development and scale up in api manufacture part 2 quality. The scaled up parameters may include such geometric ratios as d t, and zt. N and others published scale up and postapproval changes supac guidance for industry. Questions and answers on post approval change management protocols regulatory authority. The 1987 stability guideline and the 1998 draft stability guideline withdrawn in 2006 provide a good background on fda thinking with regard to stability requirements for postapproval changes. Furthermore, the fdas manual of policies and proce dures mapp.
Chemistry, manufacturing and controls cmc changes are inevitable due to many reasons including changing needs, new findings. Where process changes are introduced in late stages of. This replaces the draft guidance of the same name that combined and. Scaleup and postapproval changes how is scaleup and. This guidance combines and supersedes the following scaleup and postapproval changes supac guidances for industry. Manufacturers must optimize the process they use to make the chemical so they can scale up from a medicinal chemist producing milligrams, to. Revalidation needs to be done to ensure that changes have not take place. Immediate release solid oral dosage forms, scaleup and postapproval changes. The new draft guidance fills an important void as the existing guidance for industry. Who regulation of post approval changes to vaccines.
Changes, also refer to variations in other document, to vaccine composition, manufacturing process, quality control, equipment. Leen schellekens, mettler toledo, ucd engineering building, 19th oct 2004. Demonstration scale in this step, the process flowsheet is. Second edition, revised and expanded, edited by allen cato, lynda sutton, and allen cato iii 121. Sep 30, 2014 4the scale up and post approval changes supac task force which was established by the center for drug evaluation and research cder chemistry, manufacturing and controls coordinating committee to develop guidance on scale up and other postapproval changes 6 7. Scaleup and postapproval changes how is scaleup and postapproval changes abbreviated.
The final guidance encourages drugmakers to use a riskedbased approach in evaluating equipment changes during the scaleup and postapproval change supac process. The scaledup parameters may include such geometric ratios as d t, and zt. Pilot batch size should correspond to at least 10% of the production scale batch, i. Pharmaceutical process scaleup, edited by michael levin 119. Fda updates scaleup and postapproval change guidance.
Taking a process or product from the bench to viable production scale is a complex task. This leads to both speed of deployment and greater stability, as discussed in the 2014 state of devops report pdf. Process equipment, cost scaleup obtaining corporate approval for new equipment or estimating detailed costs for a new plant often require that ballpark costs be calculated quickly for different types of hardware during both predesign and design phases. Learn how the fdas supac guidance defines principles for process and compositional changes in drug product manufacturing postapproval. Furthermore, the fdas manual of policies and procedures mapp, specifically. Federal register draft guidance for industry on scaleup. This course will provide a basic understanding of the fda scale up and post approval changes guidelines the 2004 fda guideline on changes to approved. Dermatological and transdermal formulations, edited by kenneth a.
Approval change supac expert working group of the chemistry manufacturing. Process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a. Approval change supac expert working group of the chemistry. Additionally, from the regulatory standpoint, scale up and scale down are preserved with the similar degree of examination. Manufacturers must optimize the process they use to make the chemical so they can scale up from a medicinal chemist producing milligrams, to manufacturing on the kilogram and ton scale. The 1987 stability guideline and the 1998 draft stability guideline withdrawn in 2006 provide a good background on fda thinking with regard to stability requirements for post approval changes. Changes are being made in the manufacturing process and chemistry of a drug product following.
Development and scale up in api manufacture part 2. Immediate release and modified release solid oral dosage. As part of product and process development, pat methods can be used to support process understanding and facilitate scale up and commercial site transfer. Regulatory aspects of scaleup and postapproval changes are addressed. Problems associated with scale up might require changes in post approval that would affect the final formulation composition, site change, and manufacturing process or equipment changes strovel et al. Scale up changes should be properly validated and if needed, inspected by appropriate agency personnel. As part of product and process development, pat methods can be used to support process understanding and facilitate scaleup and commercial site transfer. Modified release solid oral dosage forms scaleup and postapproval changes. Additionally, from the regulatory standpoint, scaleup and scaledown are preserved with the similar degree of examination. Scalability, the ability to function with different amounts of required work, or to be readily adjusted to do so. Comparative study of regulatory requirements for post. Sterile products scale up geometric similarity employs proportional scale up of geometric parameters of the vessel.
Pilot scalepilot scale is a first view into continuous processing of a product 3. Demonstration scale in this step, the process flowsheet is closely resemble commercial scale operations. Are a series of usual process stages and a range of equipment usually employed in api manufacture important to identify critical steps and parameters in process as soon as possible specialised techniques and equipment may be employed if process will still be cost effective post approval changes type of change determines. The scale up and post approval change guidances supac and the changes to an approved nda or anda issued in april, 2004 offer a significant amount. Fda updates scaleup and postapproval change guidance 2014. Requirements for permission of new drugs approval post approval changes in biological products. Development essential before scaleup and validation get process right first time constraints a major factor have process in control critical parameters consider differences between lab and plant scale. Scale up and post approval changessupac slideshare. Q11 development and manufacture of drug substances 2012 barely touches on post approval changes and the guidance for industry. Each area of change was further divided to reflect a hierarchy of significance and hence aided in establishing postapproval change filing.
Looking for clarification on reporting postapproval changes. The size of the batches is gradually increased scaleup. Scaleup problems may require postapproval changes that affect formulation. Best practices for the development, scaleup, and post. For postapproval changes for immediate release dosage forms that affect components and composition, scaleup, site change, and manufacturing process or. It also eliminates references to specific brands of equipment used in prior guidance and replaces them with general equipment categories. Table 1 comparison between the manual and the automatic mode of controlling the.
Pqri post approval changes for sterile products working group. Guidelines on procedures and data requirements for changes. This course will provide a basic understanding of the fda scaleup and post approval changes guidelines the 2004 fda guideline on changes to approved. Scale down below 1,00,000 dosage units is not covered by this guideline. The scale up and the changes made after approval in the composition manufacturing process, manufacturing equipment and change of site have become known as scale up and. Manufacturing process changes, biologic your logo product. Regulatory requirements related to stability testing. This webinar is intended for formulators, process engineers, validation specialists and quality assurance personnel, as well as production managers occupied with process and product scale up and changes in any fda approved production. The scale up and the changes made after approval in the composition manufacturing. Immediate release and modified release solid oral dosage forms, manufacturing equipment addendum and supacss nonsterile semisolid dosage forms, manufacturing equipment addendum. Bioreactor scale up new master cell bank new formulation new purification columnresin. These may be used in the process development or optimisation stage, may be used to s upport formal stability studies and also to s upport preclinical and clinical evaluation. Sterile products scale up geometric similarity employs proportional scaleup of geometric parameters of the vessel.
37 1057 899 666 279 717 831 286 853 756 1249 528 1235 91 1133 1133 198 676 750 1270 158 79 720 589 1393 417 1255 888 819 954 983 284 1476 505 931 1313 1310 518 372