Manila Central University College of Pharmacy Manuf Midterms PDF

MANILA CENTRAL UNIVERSITY College of Pharmacy LESSON 1: Introduction to Manufacturing Pharmacy BASIC LEVELS OF TRUSTEES/BOARD OF DIRECTORS LEVEL I-Consists of the Board of Trustees or the Board of Directors & The functions are:...

MANILA CENTRAL UNIVERSITY College of Pharmacy LESSON 1: Introduction to Manufacturing Pharmacy BASIC LEVELS OF TRUSTEES/BOARD OF DIRECTORS LEVEL I-Consists of the Board of Trustees or the Board of Directors & The functions are: -higher ups 1. To protect and make the most effective use of company assets - - 2. To establish objectives and determine the basic policies and general course of the business - 3. To represent and safeguard stockholder interests - LEVEL II-Consist of the President The functions include active planning, direction, coordination and control of business within the & - - - scope of policies established and authorized by the Board or Level I. LEVEL III-Consists of the 6 Vice President, General Managers and Department Managers The functions include management of the major departments of the company. They are fully responsible and accountable to the President or Level II for the success of their respective operations. manufacturing we Research and development have in with different functions quality assurance BASIC FORMS OF ORGANIZATIONAL STRUCTURE ↳ under : Functional structure Ex Human Resources GMP Validation. , marketing sales department & , o Groups all activities on the basis of similarity of functions alone Divisionalized structure Retail company Ex O. o Combines into one unit all different kinds of work necessary to accomplish a specific result. DRUG ESTABLISHMENTS Drug Establishments > related to manufacturing - -  Any organization or company involved in the manufacture, importation, repacking and/or notdistributions of drugs or medicines really associated with manufacture Types of Drug Establishment 1. Drug Manufacturer O Types: (a. Ethical Manufacturers S 2 b. Proprietary / Generic Manufacturers & I Brands PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 1 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy 3 c. Biologicals Manufacturers - d. Veterinary Products Manufacturers 5 e. Medicinal Chemical Manufacturers ↑ - not much engage ; most people involved were is Chemist ~ O f. Toll / Contract Manufacturers and manufacture ↳ Owner' of the product ask to toll Ap 00 2. Drug Importer/exporter/distributor ②  Imports or exports raw materials, active ingredients or finished products for its own use or for - ⑧ wholesale distribution on whole sale basis - 3. Drug Trader distribution & marketing of the products  registered owner of the drug product but subcontracts - ⑧ toll manufacture of such products to a - licensed & manufacturer ⑳  May also engage in distribution and or marketing of products 7 Departments in a Pharmaceutical Company I  Marketing 2  Research 3  Production  Quality Control -  Engineering manuf VS. DDS Lower Form  Purchasing - Applying - · higher form of technology  Medical more on traditional of technology small scale PART II. PLANT DEPARTMENT Larger scale - - D Pharmaceutical Manufacturing o Complete set of activities to produce a drug that comprise production and quality control from O - dispensing of materials to the release for distribution of the finished product difference o Manufacture, propagation, preparation and processing of a drug product in - - - a large scale o the making by physical, chemical, biological or any other procedure of any article that meets the definition of drugs Follow EDA guidelines packaging labelling in , o Manipulation, sampling, testing or control procedures applied to the final product or any other part of the process the packaging, repacking or changing the container, wrapper or label of any drug package in preparation for its distribution from the manufacturer to the final user MARKETING - PRODUCTION PLANNING ⑮BASIC STEPS IN THE MANUFACTURE OF MOST DOSAGE FORMS Q - - - - Assuring the availability of proper compounding and packaging equipment - - ⑳ Gathering and carefully weighing or measuring raw materials PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 2 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy ③ Processing ⑪ Forming the finished products ⑤ Packaging and labeling the product Purchasing Section - - Inventory control 3 A. SECTIONS OF PRODUCTION CONTROL & planning and scheduling ② 1. Purchasing Section E In charge of purchasing requisitioned items for the company, both from& local and imported sources - = O 2. Inventory Control Watches closely and records all materials used in production, controls the stock of both us raw materials and finished products planning a scheduling Check the stocks periodically · O 3. Planning and Scheduling Coordinates with⑧ Marketing on what products are required for supply, and then plans and schedules the manufacturing of the product. Then through a manufacturing order (M.O.) the production department manufactures theC = quantity scheduled at the time limit allowed. 5 sections of Warehouse division : ⑬ B. SECTIONS OF THE WAREHOUSE DIVISION ① Rawmaterials & Returned Goods 1. RAW MATERIAL: ② in process ⑤ Dispensing This section is consisting of 3 subdivisions: ③. Finished Product indisting a. Quarantine Area use Barcode c. Rejected Area 7 b. Approved for Use Area contains colored labels ; nowadays we When Finished product QC is passed = undergo quarantined, Approved , Rejected QUARANTINED MATERIALS yellow Are labeled QUARANTINE & Implies that the materials are subject to tests and assays by Quality Control and are not to be used in production APPROVED FOR USE MATERIALS ↳ en - Labeled with a green label with bold letters APPROVED FOR USE T PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 3 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy Materials from QUARANTINE AREA are found to conform to standards and specifications and are transferred to the APPROVED FOR USE AREA replacing the ① QUARANTINE label with green label. REJECTED MATERIALS ↳ Red - - O Those found to be substandard and are transferred from the QUARANTINE AREA to the REJECTED AREA replacing the QUARANTINE label with red label containing the bold letters REJECTED. · passed (such leak · These materials are either returned to supplier or destroyed moisture QU packed it Integrity of Packaging in > - once. , 2. In-Process Consists of the products which have been bottled - or stripped, packed but not yet labeled or packed into boxes or cartons because they are awaiting Quality Control tests and assays and final disposition In not Des yet packed or labeled , distribution a sale 3. Finished Products - This area contains the products packaged and finished and are ready for - distribution and sale 4. Returned Goods - placed in another warehouse pendingsition ① > Goods returned are stored in a section of the Warehouse Quality Control - pending disposition by - 5. Dispensing Area Consists of weighing , Balances - Dispensing , Area in the Warehouse where raw materials for use in the production are - in weighed and/or measured. Dispensing raw materials - used - - weighed for measured. Includes a supervisor, checker and Quality Control Inspector/s C.ENGINEERING AND MAINTENANCE SECTION Takes charge of the care and maintenance of all machines used in the Plant Department & Right Master 000 including electric lines, water lines, repair of defective equipment Formula PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 4 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy : Revit only DosageForms : Part III. MANUFACTURING OF PHARMACEUTICALS - more on Experimenting The general procedures for manufacturing of a product are as follows: - formulation Master Formula Master Formula : Focused Apl ingredients - on C Name of the product name -Potency ② Potency of the ingredient Batesize manuf vidia's · · 11) TOF-Ing e Batch size, amount of yield Size Applying the concept of - · Briz im p knt ② · List of ingredients and specifications and code numbers posageForms -high yield experiment e Quantity of each ingredient PRODUCTION CONTROL and product Signature of competent people who prepared it creating MANUFACTURING ORDER and also executing signature Scheduled date of them reff to production the aiteria in WAREHOUSE (DISPENSING) M.O.Number PRODUCTION the market master Formula manufacturing order M.O. + Finishing Order o Name Of Product number Focused the - · Batch size MANUFACTURING SECTION on · Potency PACKAGING SECTION quality of the List · all ingredients specifications, code number WAREHOUSE (IN PROCESS AREA) , · signature product Quantity Ingredients · of QC checks, tests and assays · warehouse manufacturing Order date * PACKAGING SECTION o scheduled dispensing 0 M O. number WAREHOUSE FINISHED PRODUCT SECTION ⑳ o packaging section CLASSIFICATION OF PHARMACEUTICAL PREPARATIONS COMMONLY MANUFACTURED IN LARGE SCALE ⑤ I.LIQUID A. SOLUTIONS - 1. Aqueous Solution 2. Sweet or Other Viscid Aqueous Solutions based oil injectable oil 3. Non-Aqueous Solutions can only be seen from cod liver - , B. EMULSIONS ~ 1. Oil in Water Type 2. Water in Oil Type C.SUSPENSIONS - 1. Gels > can be alsodemi-solid but - included not 2. Lotions 3. Magmas and Milk 4. Mixtures E II.SEMISOLIDS 1. Ointments - 2. Creams 3. Transdermal Drug Delivery Systems - PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 5 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy &insectamanita bl III.STERILE PRODUCTS 1. Small and large Volume Injectable Preparations or Injections 2. Biological Preparations. slente 9 product : 3. Irrigation Fluids Injectable Biological 4. Opthalmic Preparations Irrigation 5. Dialysis Solutions opthalmic 6. Pellets or Implants Dialysis Pellets Implants or IV. Tablets V. Capsules VI. Pharmaceutical Aerosols - VII. Cosmetics - PART IV. CURRENT GOOD MANUFACTURING PRACTICES (Gmp) Code al of the chapter Current Good Manufacturing Practices (cGMP) of FederalRegulation ⑧ part 211 o Chapter⑧ 21 of the Code of Federal Regulations Part 211 o were first promulgated by the US Food and Drug Administration (FDA) in⑧ 1963; and finalized in &1979 o Part of quality assurance which ensures that products are consistently produced and controlled to = - - the quality standards appropriate to their intended use (WHO 2007) - o System of quality assurance aimed at ensuring that products are consistently manufactured to a - quality appropriate for intended use and is concerned with manufacturing and quality control - - - - process and procedures (A.O.43 s. 1999) - A s 1999 o Part of quality assurance which ensures that medicinal products are consistentlye produced and e controlled to the quality standards appropriate to their intended use. CGMB Administrative order 43 1999-1st edition by FDA Philippine GMP Regulation AO 43 1999- adoption of the⑧ 1st edition of the current GMP guidelines by FDA padaptation ↑ a implementation AO2012-0008- adoption and implementation of the PIC/s GMP as the standard on the adoption and implementation of manufacturer Administrative Order 2012-0008 - PICS FDA MC 2012- Philippine FDA mandated all drug manufacturers to ensure strict and full O compliance to the newly adopted PICS FPAMC 2012 FDA mandated - Pharmaceutical all ang manus to Chapters of PIC/s GMP 2009· Inspection convention ensure strict & I. Quality management ① Quality Full compliance II. Personnel management personnel adoptio III. Premise and equipment ⑥ newly ③ Premise & Plus equipment PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 6 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy IV. Documentation V. Production VI. Quality control VII. Contract manufacture and analysis VIII. Complaints and product recall IX. Self-inspection all manufacturing process must be Basic Requirements of GMP (PIC/s 2009) crearly defined -O importan 1. All manufacturing processes are clearly defined, systematically reviewed in the light of experience - and shown to be capable of consistently manufacturing medicinal products of the required quality and complying with their specification 2. Critical steps of manufacturing process and significant changes to the process validated ⑧ 3. All necessary facilities for GMP are provided including A Change control A. appropriately qualified and trained personnel Adequate premises and space * In manut what is the definition of Qualified personnel ? , C. Suitable equipment and services trained and capable to - D. Correct materials, containers and labels do the work E. Approved procedures and instruction F. Suitable storage and transport 4. Instructions and procedures are written in an instructional form in an unambiguous language specifically applicable to the facilities provided 5. Operators are trained to carry out procedures correctly 6. Records are made, manually and or by recording instruments, during manufacture which demonstrates that all the step required by the defined procedures and instructions were in fact taken and that the quantity and quality of the product was as expected. If not recorded It is not happen , Any significant deviations - - are fully recorded and investigated 7. Records of manufacture including distribution which enable the complete history of a batch to be traced are retained in a ->comprehensible and e accessible form 8. The distribution (wholesaling) of the products minimizes any risk to their quality q ⑳o 9. A system is available to recall any batch of product from sale or supply - 10. Complaints about marketed products are examined - o O The cause of quality defects investigated and appropriate measures taken in respect of the defective products T E => = and to prevent reoccurrence T dispense all manufactured it is not & ↑ when ↑ Problem arise should present proofs , PHARM. MANUF. LECTUREINTRODUCTION TO MANUFACTURING PHARMACY 7 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy Aug 21 , 2024 LESSON 2 Product Life Cycle Management product life cycle & any product has & must have contingent Plan PART 1. HISTORICAL PATTERN OF PRODUCT LIFE CYCLE - - The life story of most successful products is a history of their passing through certain recognizable stages as shown in Figure 1. * If the product ⑧ - - product is generic , ↓ Introduce the product ! it has a lot of competitors. in market. AtFirst = hindi siya mapenta * improvermarketing in generic unless it is very needed Strategy 10 ⑧ drugs depends needs s ↓ on the & EX Ritmed no more. se growth * same formulation - due - day as to competitor sales B slowly increasingmarket by introducing in & - - - G - F ⑧ - - - O - ⑧ T 5 5 5 - created - " 5 Figure 1. Product Life Cycle Stage⑧ 1. Market Development This is when a new product is first= brought to market, before there is a proved demand for it, and often before it has been- = fully proved out technically in all respects. Generally, demand - has to be “created” during - the product’s initial market development stage. How long this takes depends on the product’s complexity, - - its degree of newness, its fit into consumer needs, and the presence of competitive substitutes of one form C. > > - companympopuaamgumtigovernmenta or another. inpharmaceutical Examples: 3rdwond Gantrydonotmakeorphandy aunited - states 1. A proved cancer cure would require virtually no market development; it would get immediate massive - - - support. trial => There must be a sueting cincal ↳ Example of wax process · 2. An alleged superior substitute for the lost-wax process of sculpture casting would take lots longer. production - · m Customer focused needs when producing a product PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 1 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy ② While it has been demonstrated time after time that properly customer-oriented new product development - is one of the primary conditions of sales and profit growth, what have been demonstrated even more = - conclusively are the ravaging costs and frequent fatalities associated with launching new products. = - F O Stage 2. Market Growth Qp 4. Stage 2: take offstage & ↳ Demand begins to accelerate and the size of the total market expands rapidly. It might also be called the - - “Take-off Stage.” tar off stage market development stage ~ The usual characteristic of a successful new product is a- - gradual rise in its sales curve during the market development stage. At some point in this rise, a marked increase in consumer demand occurs and sales take · off. This is the beginning of Stage 2—the market growth stage. The ensuing fight for the consumer’s patronage poses to the originating producer an entirely new set of problems. Instead of seeking ways of getting consumers to try the product, the originator now faces the more compelling problem of getting them to prefer his brand. This generally requires important changes in = marketing strategies and methods. But the policies and tactics now adopted will be neither freely the sole O choice of the originating producer, nor as experimental as they might have been during Stage I. The presence of competitors both- dictates and limits what can easily be tried—such as, for example, testing what is the => => = => best price level or the best channel of distribution. => Stage 3. Market Maturity competing more > - - effectively ⑧O Demand levels off and grows, for the most part, only at the replacement and new family-formation rate. - - - - This new stage is the market maturity stage. The first sign of its advent is evidence of market saturation. This = => means that most consumer companies or households that are sales prospects will be owning or using the - product. Sales now grow about on a par with population. No more distribution pipelines need be filled. Price = competition now becomes intense. Competitive -- attempts to achieve and hold brand preference now involve making⑳Ofiner and finer differentiations in the product, in customer services, and in the promotional practices - and claims made for the product. = Typically, the market maturity stage forces the producer to concentrate on holding his distribution outlets, retaining his shelf space, and, in the end, trying to secure even more intensive distribution. Whereas, during ⑳ the market development stage, the originator depended heavily on the positive efforts of his retailers and distributors to help sell his product. Retailers and distributors will now frequently have been reduced largely to being merchandise-displayers and order-takers. In the case of branded products in particular, the - - - - - originator must now, more - - than ever, communicate directly with the - consumer. The market maturity stage typically calls for a new kind of emphasis on competing more effectively. The originator is increasingly forced to appeal to the consumer on the basis O of price, marginal product O differences, or both. Depending on the product, services and deals offered in connection with it are often = PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 2 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy the clearest and most effective forms of differentiation. Beyond these, there will be attempts to create and promote fine product distinctions through packaging and advertising, and to appeal to special market segments. X ① = Stage 4.-Market Decline ⑨ The product begins to lose consumer appeal and sales drift downward. When market maturity & tapers off O & and consequently comes to an end, the product enters Stage 4—market decline. In all cases of maturity and - - decline, the industry is transformed. - Few companies are able to weather the competitive storm. As demand declines, the overcapacity that was = = = - already apparent during the period of maturity now becomes - endemic. Some producers see it coming but feel that with & = - - proper management and ecunning they will be one of the survivors after the industry-wide deluge they so clearly foresee. S To hasten their competitors’ eclipse directly, or to frighten them into early voluntary withdrawal from the industry, they initiate a variety of aggressively depressive tactics, propose mergers= - or buy-outs, and --- generally engage in activities that make life thanklessly burdensome for all firms, and make death the inevitable consequence for= - - ~ - - most of them. - A few companies do indeed weather - the storm, sustaining life through the constant - descent that now clearly characterizes the industry. Production gets concentrated into fewer hands. Prices and margins get -- depressed. History of Product Lifecycle Management (PLM) entireestyle ni aga ⑧ The concept of a product having stages of life (and the need to manage them) arose as early as 1931. ② Around 1957, an employee of Booz, Allen and Hamilton, the advertising agency, theorized a five-step life cycle for goods, beginning with the introduction phase, rising through growth and maturity, and = eventually hitting saturation and decline. Eventually, PLM developed as a manufacturing and marketing tool for businesses seeking to maximize the ⑧ advantage of bringing new products to the market first. PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 3 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy in business-decision making Guide us Product Lifecycle Management (PLM) ⑧ a Product lifecycle management (PLM) refers to the handling of a good as it moves through the typical = stages of its product life: development and introduction, growth, maturity/stability, and decline. This & involves both the manufacturing of the good and the marketing of it. The concept of product life handling cycle helps inform business decision-making, from pricing and promotion to expansion or cost-cutting. Effective product life cycle management brings together the many companies, departments, and employees involved with the product's production to& streamline their activities, with the ultimate goal of ⑧ producing a product that outperforms its competitors, is highly profitable, and lasts as long at consumer desire and technology permit. * Pharmacist in marketing aside from , highsalary in all information and , product market they, also responsible marketing strategy Identifying which stage of its life cycle a product is in determines how it will be marketed. For example, a new product (one in the introduction stage) needs to be explained, while a mature product needs to be differentiated. PLM can affect more fundamental elements of a product, too. Even after it reaches - maturity, a product can-still grow—especially if it is updated or augmented in some way. * life of product sales - Newpro-needs explain depends on marketing mature product needs to diferentiated Benefits of Product Lifecycle Management * should have good - a marketing strategy Sound product lifecycle management has many benefits, such as getting the product to market = faster, putting a higher quality product on the market, improving product safety, increasing sales opportunities, - = and reducing errors and waste. * Do you have special Skills ? Other benefits include: Benefits include : quality & reliability ⑦ improved product c st prototyping & Improved product quality and reliability - ② Reduced => sales 2 Reduced prototyping costs identication of > ③ Quick y opportunities grevent contributions - Quick identification z of sales opportunities and revenue contributions - the re-use ⑦ savings through = & Savings through the re-use of original data * of original dat - - a S A framework for product optimization - - - ↳ E Reduced waste ⑤ Framework for product 18 Improved ability to better manage seasonal fluctuation management ptimization · , ⑥ reducedwaste * 2 * * 0 Improved forecasting to reduce material costs &. E & & Maximized supply chain collaboration ⑦ Ability to better manage & Sessional fatuation manage ⑧ Forecasting to reduce ment Pharmaceutical Product life cycle material ⑨ maximized supply chair ① ⑳ A product's life cycle refers to a set of regulatory, administrative, and monitoring activities but the concept is of major importance in the prevention of adverse drug reactions and in the maintenance of a positive ei benefit/risk ratio of a health product during its entire life. PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 4 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy Because this life cycle refers to all stages preceding and following the marketing of a health product, it includes the following steps: the sale of product allow the e decision whether to product. D a. discovery of the product; a discovery of the ↓ preclinical studies a. 2 b. preclinical studies; C Clinical trials. c. clinical trials; d presentation ofproductnufacturer d. presentation of product information by the manufacturer to the regulatory agency for its evaluation and approval; e. decision whether to allow the sale of the product; f. distribution and sale of the product; g. monitoring, inspection, and post-marketing investigations. The ultimate goal is to ensure that patients have access to efficient and safe health products not only as - - - participants during clinical trials but also in real life following the marketing authorization of these health - - - - products. The pharmaceutical product life cycle comprises all the pharmaceutical processes from drug discovery through launch to access. These activities are monitored closely by the regulators, who intercept at the strategic decision points as shown in Figure 2. Q ①pre-discovery research ② ⑥ Discovery ③ Pre-clinical , laboratory & Animal studies ⑨ ③ EarlyFormulation development ⑤ Clinical trials & ⑦ & ⑰ ⑧. late Formulation Approval Pricing and development listing ⑦ ⑨ marketing ⑳ ⑤ Figure 2 shows the monitoring activities of the regulatory agencies as a variety of regulatory activities divided into a continuum. Thus, these activities can integrate and use information that continues to develop throughout the life cycle of a health product. The decision-making process is an integral aspect of drug development and determines the fate of a drug in terms of progressing to the next stage in the pharmaceutical product life cycle. PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 5 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD ⑯  MANILA CENTRAL UNIVERSITY College of Pharmacy "From / discovery to decline phase William & A Closer Look on the Product life cycle of Pharmaceuticals - McCarthy 1997) It is important to see the marketing process in the context of the complete product life cycle, from basic research to genericization at the end of the product patent. A typical product life cycle can be illustrated from discovery to decline (William and McCarthy, 1997). William & Macarthy 1997 O , The product's life cycle period usually consists of five major steps or phases: A 1. Product development ~ 2. Introduction ~ not marketing developmen 3. Growth 4. Maturity ↓ 5. Decline ~ 1.Product Development Phase ⑧ The product development phase begins when a company finds and develops a new product idea. This involves translating various pieces of information and incorporating them into a new product. A product = - undergoes several changes and developments during this stage. With pharmaceutical products, this - ⑳ depends on efficacy and safety. 2 for pharmaceutical product Pricing strategy must be developed at this stage in time forelaunch. Marketing plans, based on market - research and product strengths, for the launch and development of the product, are established and - approved within the organization. Research on expectations of customers from new products should form O a significant part of the marketing strategy. Knowledge, gained through market research, will also help to - O - O - segment customers according to their potential for early adoption of a product. Production capacity is ⑤ - = geared up to meet anticipated market demands. - 2.Introduction Phase = Product Launch Phase The introduction phase of a product includes the product launch phase, where the goal is to achieve maximum impact in the shortest possible time, to establish the product in the market. Marketing - & ① promotional spend is highest at this phase of the life cycle. Manufacturing and supply chains (distribution) - - must be firmly established during thisO - phase. It is vital that the new product is available in all outlets (e.g. - - pharmacies) to meet the early demands. - PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 6 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy entry new 3.Growth Phase -accepts ⑳ The growth phase is the time the when the market accepts the new entry and when its market share grows. The maturity of the market determines the speed and potential for a new entry. If the new product is highly innovative relative to the market, or the market itself is relatively new, its growth will be more rapid. Marketing becomes- more targeted and reduces in volume when the product is well into its growth. Other - aspects of the promotion and product offering will be released in stages during this period. A focus on the - efficiency and profitability of the product comes in the latter stage of the growth period. ad 4.Maturity Phase no longer stabilize ; may stabilize but with litire or no expansion The maturity phase comes when the market no longer grows, as the customers are satisfied with the ⑤ - choices available to them. At this point the market will stabilize, with little or no expansion. New product = - entries or product developments can result in displacement of market - => share towards the newcomer, at the expense of an incumbent product. This corresponds to the most profitable stage for a product if, with =>>>>>> - - little more than maintenance marketing, it can achieve a profitable return. - ⑳ A product's branding and positioning synonymous with the e e quality and reliability demanded by the customer will enable it to enjoy a= - longer maturity phase. The achievement of the image of ‘gold standard’ O for a product is the goal. In pharmaceutical markets around the world, the length of the maturity phase is O - ⑤ longer in some than in others, depending on the propensity of physicians to switch to new medicines. increased competition 5.Decline Phase - - - - e The decline phase usually comes with increased competition, reduced market share and loss of sales and O profitability. Companies, realizing the cost involved in defending against a new product entry, will tend to - reduce marketing to occasional reminders, rather than the full-out promotion required to match the - - - - O e challenge. With pharmaceutical products, this stage is generally realized at the end of the patent life of a - ⑧ medicine. Those companies with a strong R&D function will focus resources on the discovery and - - development of new products. = PHARM. MANUF. LECTURE PRODUCT LIFE CYCLE MANAGEMENT 7 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy LESSON 3 Pharmaceutical Quality System PART 1. Quality Risk Management CQRM) Quality Risk Management (QRM) is the overall and continuing process of appropriatelye managing risks to e - - product quality throughout the product's life-cycle in order to - optimize its benefit–risk balance. It is a 00eee systematic process for the assessment, control, communication and review of risks to the quality of the ② medicinal product. 2 Principles of Quality Risk Management ORM The evaluation of the risk to quality should be based on: 1. Scientific knowledge ~ ~ J part of QRm -dynamic , iterative & responsive 2. Linked to the protection of the patient methodologies The level of effort, formality and documentation of the QRM process should be commensurate with the level of risk. In addition to the two principles, the following principles are also part of the QRM methodology: When applied, processes using QRM methodologies should bee dynamic, iterative and eresponsive to change and that the capability for continual improvement should be- process. embedded in the QRM - - Figure 1 shows the overview of a typical quality risk management. ⑦ management Q Initiate quality risk process # Risk assessment & Risk identification. 2 Risk analysis. 3 Risk Evaluation · Control Ki I. Risk Reduction Risk. 2 Risk acceptance communication * ② output/Result of the quality risk management process T Risk Review 1. Review Events > - I Risk management tool PHARM. MANUF. LECTURE Pharmaceutical Quality System 1 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy Decision Decision points are not shown in the Figure 1 because decisions can occur at any point in the process. & The decision might be: to return to the previous step and seek further information; to adjust the risk models; or even to terminate the risk management process based upon information that supports such a decision. Face 5The approach described in these guidelines may be used to: a. systematically analyzes products and processes to ensure that the best scientific rationale is in place to improve the probability of success; - b. identifies important = knowledge gaps associated with processes that need to be understood to properly identify risks; c. provides the =communication process that will best interface with all relevant parties involved in the - - E QRM activities; d. facilitates the -transfer of process knowledge and product development history to ease product - - progression throughout its life-cycle - e. supplements already available knowledge about the product; enable the pharmaceutical industry to - - adopt a risk-based approach to development. FPP In recognizing risks and knowledge gaps, the - QRM process plays a significant role in proactively enabling - the prioritization and mitigation of risks. The objective is to develop the⑧ FPP through maximizing product and process knowledge and risk mitigation. As& FPP development progresses, in addition to supporting that development, the purpose of the QRM process is to determine and manage risks to bioavailability, safety, ---- and efficacy and product quality. - The long process of product development is inevitably complex and requires the continual exchange of data, decisions and updates both internally within companies and, where required, with external - stakeholders. A crucial aspect of product development and QRM is the maintenance of an effective and secure knowledge management and documentation system. Such a system must facilitate transparent communication and the highlighting of key issues to stakeholders and must also include a well-structured archive. QRM Quality Risk Management Process kinitiatiating process 3 Identify. leader the and necessary resources ① Define the problem ①Initiating a QRM process ② Assemble background information &. Specify the time deliverables , QRM activities should be performed using systematic processes designed to coordinate, facilitate and improve science-based decision-making with respect to risk. The possible steps to be taken in initiating and planning a QRM process might include the following: 1. O Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk. 2. Assemble background information and/or data on the potential hazard, harm or human health impact relevant to the risk assessment. PHARM. MANUF. LECTURE Pharmaceutical Quality System 2 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD  MANILA CENTRAL UNIVERSITY College of Pharmacy 3. Identify a leader and the necessary resources. 4. Specify a timeline, the deliverables, and an appropriate level of decision-making for the risk management process. Personnel involved in QRM The implementing party, i.e. the pharmaceutical manufacturer or regulatory authority, should assure that personnel with appropriate product-specific knowledge and expertise are available to ensure effective planning and completion of QRM activities. This may be best accomplished by assembling a multidisciplinary team according to the guidance.. 5 Risk review monitoring 1 ConductLisk analysis. , ad venization 6 The personnel appointed should be able to:. Identify and analyze the potential C risk I a. conduct a risk analysis 3. Evaluate the risk Impact of c risk 2 b. identify and analyze potential risks. 4 Recommend and implement risk Finding control measures 3 c. evaluate risks and determine which ones should be controlled and which ones can be accepted 4 d. recommend and implement adequate risk control measures 5 e. devise procedures for risk review, monitoring and verification G f. consider the impact of risk findings on related or similar products and/or processes. -- Risk Assessment ⑳ When risk assessment is conducted, safety and efficacy need to be considered in addition to the quality concerns. During the assessment, all the risks that may reasonably be expected to occur when conducting - the activity under evaluation should be listed. This is usually done when the risk assessment is made for - the first time, i.e. initiated, when there is a change or a concern and may also be applied to existing processes. An analysis should be conducted to identify which risks it is essential to eliminate or to reduce to acceptable levels. A thorough risk assessment is required to ensure effective risk control. Risk assessment should review the materials, operations, ---- equipment, storage, distribution and intended - use of the product. Typically, a list of the potential risks (biological, chemical and physical) which may be - - introduced, increased or controlled in each area should be drawn up. - In the risk assessment the following basic questions should be addressed: 1. What might& go wrong? 2. What is thee nature of possible risks? e of their occurrence and how easy is it to detect them? 3. What is the probability e 4. What are the consequences (the severity)? It should then be decided which of the potential risks should be addressed by the QRM activities and what - - control measures, if any, should be taken for each risk. If a risk has been identified at a step where control PHARM. MANUF. LECTURE Pharmaceutical Quality System 3 PREPARED BY: KARINA MARIE S. BATU, MSPH, PHD &  - MANILA CENTRAL UNIVERSITY College of Pharmacy is necessary for safety, and no control measure exists at that step or at any other, the product or process should be modified at that step, or at an earlier or later stage, to include such a control measure. More than one control measure may be required to control a specific risk and more than one risk may be controlled by a specified control measure. ↓ one control measure required control Normally, potential risks in relation to the following should be considered: a -materials and ingredients; a specific Risk -physical characteristics and composition of the product; & more than -processing procedures; one risk 1 materials d Ingredients -microbial limits, where applicable;. may be controlled -premises;. 2 Physical characteristics by specific control procedure -equipment;. processing 3 measure limits -packaging; 4 microbial -sanitation and hygiene; 5. Premises equipment -personnel (human error); 6. 7 Packaging -utilities;. 8 Sanitationhygiene. -supply chain 9 personnel. 10 · Utilities 11 , Supply chain The output of a risk assessment is either a quantitative estimate of risk (numeric probability) or a qualitative description of a range of risk (e.g. high/ medium/low) and may be related to a risk matrix. The scoring system and trigger points for mitigating action are subjective so the rationale for score categorization should be defined in as much detail as possible. If the score and trigger action are supported by factual evidence, it should be more obvious what mitigating action is required – the mitigating action is as important as the score assigned. - - = Professional judgement should be used in interpreting the factual evidence but must be subject to justification. Records of risk assessments should be maintained. The expectation of QRM is to assess risks - to the product quality and to the patient and then manage these risks so that they are kept at an acceptable level. Risk Control Risk control is a decision-making activity designed to reduce and/or accept risks. It usually occurs after risk assessment, and at a fundamental level its purpose is to reduce the risk to an acceptable level. During risk control activities the following key questions should be asked: 1. What can be done to reduce or eliminate risks? 2. What is the appropriate balance between benefits, risks and resources? 3. Are new risks introduced as a result of the identified risks being controlled? - PHARM. MANUF. LECTURE Pharmaceutical Quality System 4 PREPARED BY: KARINA MARIE S. BATU, MSPH