Introduction to pilot plant and scale up technology

This presentation include basic introduction to pilot plant and scale up technology. following points are definition, objective , process evaluation, SUPAC , advantages and dis advantages etc

1. Pilot Plant And Scale Up Technique Introduction Presented By –Vasanti G. Patil M. Pharm First Yr.(QAT) 2019/020 Roll No. 26 Guided By – Dr. S.Daswadkar 1

2. Content Definitions Introduction Discussion Objective Process evaluation SUPAC Advantages Disadvantages Layout pf pilot plant of Tablet Case study of production ( SUNPHARMA ) Conclusion Growth chart of Indian pharma industry up to2019 References 2

3. Plant :- It is a place were the 5 M’s like money, material, man, method and machine are brought together for the manufacturing of the products. Plant of Torrent pharmaceuticals 3

4. Pilot Plant :- It is the 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. 4

5. Scale-up :- The art for designing of prototype using the data obtained from the pilot plant model 5

6. Pilot scale and scale up process 6

7. Pilot Scale and Scale-Up Means 7

8. Objective To try the process on a model of proposed plant before committing large sum of money on a production unit. Examination of the formula to determine it’s ability to withstand Batch-scale and process modification. Evaluation and Validation for process and equipments To provide master manufacturing formula with instructions for manufacturing procedure. To avoid the scale-up problems. 8

9. Why conduct Pilot Plant Studies? It is not possible to design a large scale processing plant from laboratory data alone with any degree of success. It is usually not possible to predict the effects of a many-fold increase in scale. 9

10. Continue…… It Gives rough idea about physical space required and of related functions. Production rate adjustment after considering marketing requirements. Appropriate records and reports are issued to support good manufacturing practices. 10

11. Development process for formulation Development batches  11

12. Laboratory scale batch • Early development at laboratory stage. • It is generally 100-1000 times less than production batch. • It is 1X (3-10 kg or 3-10 liters or 3000-10000 unit) batch . Uses • To support formulation. • For packaging development. • For preclinical trial. 12

13. Pre-exhibit batch • It is 1st step in scale up. • It generally 70 % of the size of the exhibit batch. • It prepaid with the complete process documentation and fully validated analytical methodology. Uses • To detect any problem arise in manufacture of exhibit batch . 13

14. Exhibit batch It is demonstration batch. It contains the mfg. documentation, product specification, accelerated stability data submitted to FDA. It generally 10 % of the production scale batch. It is 10X (30-100 kg or 30-100 liters or 30000-100000 unit) batch. It is manufactured under GMP . 14

15. Exhibit batch also called as :- NDA or ANDA batch Regulatory reference batch Bioequivalence batch Fully GMP batch Stability tested batch 15

16. Production batch It is produced during the routine marketing of product. It is 100X batch means :- 300-1000 kg or 300-1000 liters or 300000-1000000 unit 16

17. What is Scientific scale up Should done in incremental manner. Process being validated for each new scale. The equipment should possess following similarity 1) Geometric similarity 2) Kinematic similarity 3) Dynamic similarity 17

18. 18 General considerations

19. 2. Personnel Requirement :-  Scientists with experience in pilot plant operations. As they have to understand the intent of the formulator as well as perspective of the production personnel. personnel with engineering knowledge 19

20. 20 3.Space Requirement Administration And Information processing Physical Testing Area Standard Equipment Floor Space Storage Area

21. 21 3. Administration and information process: Adequate office and desk space should be provided for both scientist and technicians. The space should be adjacent to the working area .

22. 22  4. Physical testing area:- This area should provide permanent bench top space for routinely used physical- testing equipment

23. 23 5  . Standard pilot-plant equipment floor space:- Discreet pilot plant space , where the equipment needed for manufacturing all types of dosage form is located . Intermediate – Equipments used should be made portable where ever possible. Space for cleaning of the equipment should be also provided. floor space Epoxy coating PVC coating

24. 24 5.Storage Area:-  It should have two areas divided as approved and unapproved area for active ingredient as well as excipient . Different areas for the storage of the in-process materials, finished bulk products from the pilot-plant & materials from the experimental scale-up batches made in the production. Storage area for the packing material.

25. 25 Review of the formula The purpose of each ingredient and it’s contribution to the final product should be understood. Then the effect of scale-up using equipment that may subject the product to stresses of different types and degrees can more readily be predicted, or recognized.

26. 26 5 . Raw materials checking Raw materials used in the small scale production cannot necessarily be the representative for the large scale production 

27. 27 6. Equipment:- economical , simplest & efficient equipment The size of the equipment should be relevant. If the equipment is too small the process developed will not scale up. Whereas if equipment is too big then the wastage of the expensive active ingredients.

28. 28 Process Evaluation Parameter

29. 29   Master Manufacturing Procedures:- The three important aspects Weight sheet Processing directions Manufacturing procedure 

30. 30 Scale-up and post approval changes (SUPAC) FDA and American Association of Pharmaceutical Scientists (AAPS ) provided the scientific foundation for the scale up and post approval changes required for immediate release product Called as SUPAC. It provide guideline for post approval changes in the following Component Composition Site of mfg. Process and equipment 

31. 31 Advantages Members of the production and quality control divisions can readily observe scale up runs. Supplies of excipients & drugs, cleared by the quality control division, can be drawn from the more spacious areas provided to the production division. Access to engineering department personnel is provided for equipment installation, maintenance and repair. 

32. 32 Disadvantages The frequency of direct interaction of the formulator with the production personnel will be reduced. Any problem in manufacturing will be directed towards it’s own pilot-plant personnel's.

33. 33 LAYOUT OF TABLET PILOT PLANT

34. 34 Case Study The case study critically examines the supply chain strategy of ‘SUN pharma’ company and its acquisition strategy of Ranbaxy. The case illustrates the story of the mergers and acquisition from a supply chain theory point of view and thereby states how SUN has moved forward from its regional presence to global expansion.

35. 35 Sun Pharma's annual sales revenue before and after the acquisition of Ranbaxy

36. 36 Before merge, Ranbaxy used Aqua Logistics services to track and trace the shipments in order to avoid distribution centres at various overseas and domestic locations by keeping track of the current position of the shipment dispatched by it. To enhance global supply chain capability Sun Pharma, used Radio Frequency Identification ( RFID) technology replacing their bar coding system in order to track the stocks automatically .

37. 37 INDIAN Pharma Industry Growth Chart

38. 38 Conclusion :- A pilot plant is a small industrial system which is operated to generate information about the behaviour of the system for use in design of larger facilities. Pilot plants are used to reduce the risk associated with construction of large process plants To avoid the scale-up problems.

39. References :- The theory & practice of industrial pharmacy by Leon Lachman, Herbert A. Lieberman, Joseph L. Kenig, 3rd edition, published by Varghese Publishing house. “Pharmaceutical process scale –up” by Michael Levin marcel dekker inc volume-157, 2003. “Pharmaceutical process validation” by Robert A. Nash and Alfred H Wachter marcel dekker inc volume-129, 2003 . Page no. 17-21. 5. “Text book of industrial pharmacy” by Shobha Rani R. Hircmath, orient Longman pvt ltd Chennai .  39

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