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  Fig. 2.1: Reporting responsibilities under general considerations 10 Industrial Pharmacy II scale-up and the pilot-plant should have practical experience in pilot-plant operations. The level of education and type of education should be matched within the group because they have to understand each other perspective. The group should have personnel from different disciplines like engineering, economics, management, production, etc. The scientists with experience in pilot-plant production as well as actual production area should be preferred. The number of personnel required depends upon the number of products being supported and the level of support. 2.1.3 Space Requirements There are four types of space requirements of a pilot-plant i. Administrative and information processing ii. Physical testing area iii. Standard pilot-plant equipment floor space iv. Storage area Administrative and Information Processing i. Adequate space should be there. ii. Scientist and technicians should have a

  2.1.5 Raw Materials One of the main responsibilities of the pilot-plant is to validate and approve the excipients and active ingredients used in pharmaceutical product's formulation. The raw materials used in laboratory-scale production may not fit for the large-scale production batches. There may be several variations in size, shape, density, and solubility, flow properties, etc. A single supplier may not be able to fulfil the need of raw material for large-scale production and can leave the manufacturer defenceless. So, several batches with different alternatives to raw materials (supplied by two or more suppliers) need to be manufactured. All the data regarding the performance of this different raw materials (stability, quality tests, etc.) should be well-documented so that can be thoroughly analysed. 2.1.6 Equipment On small and laboratory-scale basic equipment has been used during the development of drug product. So during scale-up alternative manufacturing equipment should

  1. a 2. a 3. a 4. a 5. d 6. c 7. 1(d), 2(c), 3(a), 4(b) 8. a. money, material, machine b. prototype, pilot-plant c. laboratory d. scale-up e. calibration, QA QC activities, labelling. General Considerations and Pilot-Plant Considerations for Different Dosage Forms 9 2.1 GENERAL CONSIDERATIONS (Fig. 2.3) General consideration includes the following points to be kept in mind while planning for scale-up. 2.1.1 Reporting Responsibilities (Fig. 2.1) There should be adequate records and reporting arrangements to make the transfer of products from laboratory-scale to a commercial-scale smooth. The transfer is a multidisciplinary approach as it includes pilot-plant group and other groups like R&D, processing, engineering, quality assurance, regulatory, marketing, etc. There should be good communication and relationship between pilot-plant groups and other groups. R&D group should be with separate staffing. Production department can be under formulator and formulator can provide suppo

  ii. To review the processing equipment used in the manufacturing of a product iii. To check compliance with guidelines for production and process control iv. To conduct evaluation and validation of process v. To identify the critical characteristics of the process vi. To provide master manufacturing formula 1.3.4 Relation between Pilot-Plant and Scale-up (Figs 1.2 and 1.3) Fig. 1.2: Relations between pilot-plant and scale-up Introduction to Pilot-Plant and Scale-up 7 PRACTICE QUESTIONS Long Answer Type Questions 1. Define pilot-plant. Explain pilot-plant operations and need for conducting pilotplant studies. 2. Explain scale-up process. What are the steps in conducting scale-up studies? Short Answer Type Questions 1. What is pilot-plant? Explain the reasons for conducting pilot -plant studies. 2. Define scale-up and elaborate the need for scale-up. 3. Describe the relation between pilot-plant and scale-up. 4. What are the objectives of establishing pilot-plant? Objective Type Questio

  Introduction to Pilot-Plant and Scale-up 3 Starting up a new production unit is tricky but it would become risky if unforeseen difficulties would not be identified. At the initial stage of development the product is manufactured at laboratory-scale. It is many folds smaller than that of commercial scale. So, this is not an intelligent idea to directly transfer product from laboratory scale to commercial stage due to possibility of birth of many problems, e.g. corrosion, high cost on material, low yield, less profit, etc. So, to detect and avoid the unforeseen problems pilot-plant is used. Pilot-plant can be defined as “the manufacture of either drug or drug product by a procedure fully representative of and stimulating that used for full manufacturing scale.” Pilot-plant is a part of the pharmaceutical industry where a lab-scale formula is transformed into a viable product by development of liable and practical procedure of manufacture. 1.2.1 Reasons for Conducting Pilot-Plant Studie

  1.2.3 Pilot-Plant Operations A pilot-plant operation includes series of operational aspects. These are as follows: 1. Validation includes the following of all utility systems, process equipments, control systems so that pilot-plant can be fully validated and ensure compliance with CGMP i. DQ (Design Qualification) ii. IQ (Installation Qualification) iii. OQ (Operational Qualification) iv. PQ (Performance Qualification) 2. Training should be given in four areas i. Compliance with CGMP and other quality systems ii. Environmental and safety responsibilities iii. Compliance with SOPs iv. Technical knowledge and skills 3. Engineering support is required for i. Design, commissioning, and validation of pilot-plant facility ii. Co-ordination, direction and scheduling of ongoing operations at the pilotplant facility 4. Maintenance is required i. To compliance with CGMP norms ii. To ensure integrity of data and reliability of equipment 5. Calibration of equipment/instrument is required i. To c

  Pilot-Plant Scale-up Techniques 2 Industrial Pharmacy II The pharmaceutical industry is growing with high speed in the last few years. New drugs, as well as generic drugs, have been coming in the market. Research and development sector is also growing with good growth rate. Researchers are encouraged to use the latest processes and technologies. In short, Cona, the pharmaceutical industry, has witnessed significant innovations and inventions coming day by day. A huge sum of money is invested in the pharmaceutical production to this much loss unit. According to a recent study, developing a new prescription medicine which gains market approval is estimated to cost drug makers nearly $2 billion. One cannot afford loss after setting up a commercial production unit. So to avoid this loss, a replica of the main design has been set up but at a smallscale. This is known as pilot-plant and the data obtained from this pilot-plant is used in establishing a commercial plant is known as scale-up.

  12.4.1 NABL Vision 187 12.4.2 NABL Mission 187 12.4.3 Achievements of NABL (As per the Official Website of NABL) 188 12.4.4 Scope of NABL Accreditation 188 12.4.5 Benefits of Accreditation 189 Long Answer Type Questions 190 Short Answer Type Questions 190 Objective Type Questions 190 Summary 193 xvi Industrial Pharmacy II UNIT 5: Indian Regulatory Requirements 13. Central and State Drug Regulatory Authority of India 206 13.1 Drug Regulatory Authority 206 13.2 Central Drug Standard Control Organisation (CDSCO) 208 13.3 State Licensing Authorities (SLA) 212 Long Answer Type Questions 213 Short Answer Type Questions 213 Objective Type Questions 213 14. CTD and New Drug Approval Process in India 215 14.1 Common Technical Document 215 14.2 Certificate of Pharmaceutical Product (COPP) 217 14.3 New Drug Approval in India 218 Requirements for New Drug Approval 220 Long Answer Type Questions 221 Short Answer Type Questions 221 Objective Type Questions 222 Summary 224 Index 229 1. Introduction

  2.5 Documentation 21 Long Answer Type Questions 23 Short Answer Type Questions 23 Objective Type Questions 23 UNIT 1: Pilot-Plant Scale-up Techniques xii Industrial Pharmacy II 3. SUPAC Guidelines and Platform Technology 25 3.1 Purpose of Guidance 25 3.2 Evolution of SUPAC Guidance 25 3.3 Terminologies used in Guidance Document 26 3.4 Level of Changes 28 3.5 Type of Changes 28 3.6 Introduction to Platform Technology 37 Long Answer Type Questions 39 Short Answer Type Questions 39 Objective Type Questions 39 Summary 41 UNIT 2: Technology Development and Transfer 4. Technology Development and Transfer 50 4.1 Technology 50 4.2 Technology Development 50 4.3 Technology Transfer 50 4.4 Technology Transfer in Pharmaceutical Sciences 51 4.4.1 Reasons for Technology Transfer 54 4.4.2 Types of Technology Transfer 55 4.4.3 Methods of Technology Transfer 56 Long Answer Type Questions 57 Short Answer Type Questions 57 Objective Type Questions 57 5. WHO Guidelines for Transfer of Technology 60 5.1

  6.4.3 TIFAC (Technology Information Forecasting and Assessment Council) 95 6.4.4 BCIL (Biotech Consortium India Limited) 97 6.4.5 TBSE (Technology Bureau for Small Enterprises)/SIDBI (Small Industries Development Bank of India) 98 6.5 TOT Related Documentation 99 6.5.1 Confidentiality Agreements 99 6.5.2 Licensing 100 6.5.3 MoU 102 6.5.4 Legal Issues 103 Long Answer Type Questions 104 Short Answer Type Questions 104 Objective Type Questions 104 Summary 107 UNIT 3: Regulatory Affairs and Regulatory Requirements for Drug Approval 7. Regulatory Affairs and its Role 114 7.1 Introduction 114 7.2 Historical Overview of Regulatory Affairs 115 7.3 Regulatory Authorities 116 7.4 Role of Regulatory Affairs Department 117 7.5 Responsibility of Regulatory Affairs Professionals 119 Long Answer Type Questions 120 Short Answer Type Questions 120 Objective Type Questions 120 8. Drug Development and Non-Clinical Studies 122 8.1 Drug Development Teams 122 8.2 Non-clinical Drug Development 124 8.3 Toxi

  FDA submissions, management of clinical studies. UNIT 4 08 Hours Quality management systems: Quality management & certifications: Concept of quality, total quality management, quality by design (QbD), six sigma concept, out of specifications (OOS), change control, introduction to ISO 9000 series of quality systems standards, ISO 14000, NABL, GLP UNIT 5 07 Hours Indian regulatory requirements: Central Drug Standard Control Organization (CDSCO) and State Licensing Authority: Organization, Responsibilities, Certificate of Pharmaceutical Product (COPP), Regulatory requirements and approval procedures for new drugs. Recommended Books: Latest Editions 1. Regulatory Affairs from Wikipedia, the free encyclopedia modified on 7th April available at http, //en.wikipedia.org/wiki/Regulatory_ Affairs. 2. International Regulatory Affairs Updates, 2005. available at http://www.iraup.com/about.php 3. Douglas J Pisano and David S. Mantus. Text book of FDA Regulatory Affairs A Guide for Prescripti