Quality by Design (Q bD) : A new concept for …

1 Available online on Journal of Pharmaceutical Quality Assurance; 4(2);13-19 ISSN 0975 9506*Author for ArticleQuality by Design (QbD): a new concept for development ofquality pharmaceuticals*Amit S. Patil, AnilM. PetheSVKM s, NMIMS, School of Pharmacy and Technology Management Shirpur,Dist. Dhule, , IndiaABSTRACTQ uality by Design (QbD) has become a new concept for development of Quality pharmaceutical products,It is anessential part of the modern approach to pharmaceutical Quality ,QbD isa best solution to build a Quality in allpharmaceutical products but it is also a major challenge to the Pharmaceutical industry whose processes are fixedin time, despite inherent process and material variability,Under this concept of QbD throughout designing anddevelopment of a product, it is essential to define desire product performance profile [Target product Profile (TPP),Target Product Quality Profile (TPQP)] and identify critical Quality attributed (CQA).

2 On the basis of this we candesign the product formulation and process to meet the product attributes. This leads to recognise the impact ofraw materials [critical material attributes (CMA)], critical process parameters (CPP) on the CQAs andidentification and control sources of an emerging idea which offers pharmaceuticalmanufacturer with increased self-regulated flexibility while maintaining tight Quality standards and real timerelease of the drug product,This paper discusses the pharmaceutical QbD and describes how it can be used todevelop the pharmaceutical products well within the specifiedperiod of words: Quality by Design (QbD)Target Product Profile (TPP), Target Product Quality Profile (TPQP),Critical Quality Attributes (CQA), Critical Material Attributes (CMA), Critical ProcessParameter (CPP)INTRODUCTIONThe concept of QbDwas mentioned in the ICH Q8guideline, which states that Quality cannot be testedinto products, , Quality should be built in by Design According to ICH Q8 QbD is defined asA systematicapproach to development that beginswith predefinedobjectivesand emphasizes product and processunderstandingandprocess control, based on soundscience and Quality risk management[7].

3 QbDencompasses designing and developing formulationsand manufacturing processes which ensurespredefined product 2002, the FDAannounced a new initiative (cGMP for the 21stCentury: A Risk based Approach)[1]. This initiativeintended tomodernize the FDAs regulation ofpharmaceutical Quality ,and establish a new regulatoryframework focused on QbDrisk management, andquality initiativechallenged industry tolookbeyond Quality by testing (QbT)for ensuringproduct Quality andperformance. An importantpart ofQbD is to understand how process and formulationparameters affect the productcharacteristics andsubsequentoptimization of these parameters should beidentified in orderto monitor these parameters onlinein the production paper discusses the pharmaceutical Quality bydesign and describes how it can be used to ensurepharmaceutical Quality with emphasis on solid oraldosage forms of small molecules.

4 The pharmaceuticalindustry works hard to develop,manufacture, andbring to market new drugsand to comply withregulatory requirements to demonstrate that the drugsare safe and effective. A new approach to drugdevelopment could increase efficiencies, provideregulatory relief and flexibility, and offerimportantbusiness benefits throughout the product s life article explores the processes used in developinga market formulation and requisite supportive data,particularly in light of the industry s currentmovement toward submissions based on Quality bydesign (QbD). It outlines activities that should beperformed early in the drug development processbefore initiating manufacturing and attempting Food and Drug Administration (FDA) Office ofGeneric Drugs (OGD) has developed a question basedreview (QbR)for its chemistry, manufacturing andcontrols (CMC) evaluation of Abbreviated New DrugApplications (ANDAs).

5 QbR is a new qualityattributes. It is a concrete and practical implementationof some underlying concepts and principles outlinedby the FDA s Pharmaceutical CGMPs for the twenty-first century and Quality by Design (QbD) initiatives[12].Pharmaceutical Quality by Testing:In this system,product Quality is ensured by raw material testing,drug substance manufacturing, a fixed drug productmanufacturing process, in-process material testing,and end product Quality of raw material including drug substanceand excipients is monitored by testing. If they meet themanufacture s proposed and FDA approvedspecifications or other standards such as USP for drugAmit S. Patil, Anil M.

6 Pethe / Quality by , Vol4,Issue2, April-June, 2013,13-19 Page14substance or excipients, they can be used formanufacturing of the of uncertaintyas to whether the drug substance specification alone issufficient to ensure Quality , the drug substancemanufacturing process is also tightly controlled. Achange to the drug substance manufacturing processmay require the drug product manufacturer to filesupplements with the drug products are tested for Quality byassessing whether they meet the manufacturer sproposed and FDA approved specification. If not, theyare discarded. Root causes for failure are usually notwell understood. The manufacturers risk ongoinglosses of the product until the root causes of failure areunderstood and addressed or FDA approvessupplements to revise the acceptance criteria to passthe previously failed 1 shows asimplified Quality controldiagram under the currentquality by testing (QbT)[2].

7 Pharmaceutical Quality by Design :ICH Q8 definesquality as the suitability, of eithera drug substance ordrug product for its intended use. This term includessuch attributes as the identity, strength and QbD is a systematic, scientific, riskbased, holistic and proactive approach topharmaceutical development that begins withpredefined objectives and emphases product andprocesses understanding and process control. It meansdesigning and developing formulations andmanufacturing processes to ensure predefined productquality objectives[9]. QbD identifies characteristicthat are critical to Quality from the perspective ofpatients, translates them into the attributes that thedrug product should possess, and establishes how thecritical process parameters can be varied toconsistently produce a drug product with desiredcharacteristics.

8 In order to do this the relationshipbetween formulation and manufacturing processvariables(including drug substance and excipientsattributes and process parameters)and productcharacteristics are established and sources ofvariability identified. This knowledge is then used toimplement a flexible and robust manufacturingprocess that can adapt and produce a consistentproduct over 2 shows a simplified qualitycontrol diagram under the current Quality by Design (QbD).Enablers of Quality by Design :Knowledgemanagement and Quality riskmanagement are twoofthe primary enablers of play a criticalroleboth in development and inthe implementation ofQbD.

9 They are instrumental inachieving productrealization, establishing andmaintaining a state ofcontrol, and lastly facilitating continual brief description of thetwo enablers and their utilityis provided in the following sections[14]. Quality Risk Management: Quality risk management(QRM) is a key enabler for the development andapplication of QbD. During development, it enablesresources to be focused on the perceived critical areasthat affect product and process. It is one of the toolsthat provide a proactive approach to identifying,scientifically evaluating, and controlling potentialrisks to Quality . It also facilitates continualimprovement in the product and process performancethroughout the product life Management:Product and processknowledge management is an essential component ofquality by Design and must be managed fromdevelopment through the commercial life of theproduct, including discontinuation.

10 It is a systematicapproach to acquiring, analyzing, storing, anddisseminating information related to products,processes, and components. This also emphasizes on aIf failsIf fails,Product discardedMaterialDiscardedAcceptance criteriabased on one or morebatch data, Testing mustbe made to release batchesFig. 1: Quality control diagram using SubstanceMeeting ,MixingCompressionCoatingWith fixedProcessParameterExcipientMeeting S. Patil, Anil M. Pethe / Quality by , Vol4,Issue2, April-June, 2013,13-19 Page15transparency of information fromdevelopment tocommercial and vice versa. Prior knowledgecomprises previous experience and understanding ofwhat has been successful or unsuccessful, andrecognition of issues, problems, or risks that mayoccur and need to be of priorknowledge include the following.