Introduction, Objective; Significance; General consideration; Pilot plant scale up technique for solid, liquid and semi solids; SUPAC Guidelies; Introduction to platform technology

1. Pilot Plant Scale Up Techniques
PRESENTED BY- DRX SANDHYA PUNETHA

2. Content-
 Introduction
 Objectives
 Significance
 General consideration
 Pilot plant scale up consideration for solids, liquid orals and semi solids
 SUPAC Guidelines
 Introduction to platform technology

3. Introduction-
 Plant- It is a place where 5 M’s like- money, material, man, method and
machine are brought together for the manufacturing of the products.
 Pilot Plant- It is the part of pharmaceutical industry where a lab scale formula is
transformed into a valuable product by development of liable and practical
producre of manufacture.

4.  Scale up – It is an art of designing a prototype using the data obtained from the
pilot plant model.

5. Objectives-
Find mistakes on small scale and make profit on large scale”
1. Produce physically and chemically stable therapeutic dosage forms.
2. Review of the processing equipments.
3. Guidelines for the production and process control.
4. Evaluation and validation for process and equipments.
5. To identify critical features of the process.
6. To identify master manufacturing formula.

6.  To try the process on a model plant before committing large sum of money on
a production unit.
 Examination of master formula so that it can withstand in a batch process.
 To avoid scale- up problems.

7. Significance of Pilot Plant-
 Examination of formulae.
 Review of range of relevant processing equipment.
 Production rate adjustment.
 Idea about physical space required.
 Appropriate records and documentation to maintain GMP
.

9. Steps involved in Scale- up Techniques-
 Step 1- Define product economics based on projected market size and competitive sellingand
provide guidance for allowable manufacturing cost.
 Step 2- Conduct laboratories studies and scale up planning at the same time.
 Step 3- Define key rate controlling steps in the proposed process.
 Step 4- Conduct preliminarily studies larger than laboratories studies with equipment to be used in
rate controlling step to aid in plant design.

10.  Step 5- Design and Construct a pilot plant including provisions for process and
environment controls, cleaning and sanitizing systems, packaging and waste
material handling system and meeting regulatory agency requirements.
 Step 6- Evaluate pilot plant results ( Product and Process) including process.
Economics to make any corrections and a decisionon whether or not to
proceed with a full scale plant development.

11. General Consideration
1. Reporting responsibility
2. Personnel requirement
3. Space requirement
4. Review of formula
5. Raw materials
6. Equipments
7. Production rate
8. Process evaluation
9. Master manufacturing procedures
10. Product stability and uniformity

12. 1) Reporting Responsibility-
 Research and Development ( R&D) group with separate staffing.
 The formulator who develop the product can take into the production and can provide
support even after transition into production as been completed.

13. 2) Personnel Requirement-
 Scientists who have pilot plant operation and production areas experience are
most preferable.
 As they are able to understand the intent of the formulator and perspective of
the production personnel.
 The group should also have some persons with engineering knowledge as scale
up process also includes some engineering principles.

14. 3) Space Requirements-

15. a) Administration and information processing-
 There should be an adequate space for office and desk for both scientists and
technicians.
 Space should be adjacent to the working area.
 Computer facility should also be provided.

16. b) Physical testing area-
 This area should provide permanent bench top space for routinely used physical
testing equipments.

17. c) Standard pilot plant equipment floor space-
 Discreet pilot plant space , for the equipment needed for manufacturing of all types of
dosages forms located.
 Intermediate size and full scale production equipment are necessary for evaluating the
effects of scale up of research and formulation processes
 Equipment used should be made portable so that after use it can be stored in a small store
room.
 Space for cleaning of equipment should also be provided.

18. d) Storage area-
 There should be 2 types of storage areas- Approved storage area and
Unapproved storage area.
 Different areas should be provided for in process material, finished bulk products
from the pilot plant, materials from the experimental scale up batches made in
the production.
 Storage area for the packaging materials should also be provided.

19. 4) Review of formula-
 A thorough review of each aspect is important in the industry.
 Purpose of each ingredient and equipments used in the small scale laboratory is
very important.
 Than the problems that are generated in the industry during scale up
production can easily be recognised.

20. 5) Raw materials-
 Our puropose/ responsibility of the pilot plant is the approval of the ingredient
and excipient used in large scale production of dosage forms.
 Raw materials used for small scale production is not necessarily to be used for
large scale production.
 Ingredients may change in particle size, shape or morphology which may result
in change of bulk density, colour, rate of solubility etc.

21. 6) Equipments
 Equipments which are simplest, economical and effective are capable of
producing the product with proposed specifications
 Size of the equipment should be such that the experimental trial run should be
equivalent to the production sized batch.
 If the equipments are too small they will not take part in scale up process.
 If the equipments are too large they will create lot of wastage of the active
ingredients.

22. 7) Production Rate-
 There should be an immediate as well as future market trends requirements are
considered while determining the production rate.
 Their should be a proper demand and supply chain management which
indirectly affects the production rate.

23. 8) Process evaluation-

24. 9) Master manufacturing procedures-

25. 10) Product Stability and Uniformity-
 The primary objective of a pilot plant is to maintain physical and chemical
stability.
 Hence, stability studies are carried out for in- process materials, raw materials,
manufacturing products, finished product as well as also for packaging products.
 For this we include GMP consideration.

26. GMP Consideration-

27. Advantages-

28. Disadvantages-

29. Pilot plant scale up consideration for solids-
1. Material handling –
 Laboratory scale
 Deliver adequate amount to the destination.
 Large scale-
 Lifting drums
 More sophisticated techniques.
 Prevent crosss contamination by validation cleaning Procedure.

30. 2) Dry Blending
 Powders should be used for encapsulation or to be granulated to tablet prior to tableting
must be well blend to ensure good drug distribution.
 Inadequate blending could result in drug content uniformity variation especially when the
tablet and capsule is small and the drug concentration is low.
 Ingredients should be lumps free otherwise it could cause flow problems.

31. 3) Granulation-
 Reasons –To improve flow properties
To increase apparent density of powder
To change the particle size distribution to improve the blending properties of powder.
 Types of granulation- Dry granulation, wet granulation , direct compression.

32. 4) Drying-
 Drying can be done with the help of various equipments depending on our
needs.
 Hot air oven- Air temperature,Rate of air flow, Depth of granulation on trays.
 Fluidised bed dryers- Optimum load, Rate of air flow, Inlet air temperature,
Humidity.

33. 5)Reduction in Particle size-
 Particle size to particle size distribution is important for the compression
characteristic of granulation.
 Compression factors that may affect from particle size distribution are- flow
ability, compressibility, uniformity of tablet weight,

35. 6) Blending-

37. 7) Slugging-

38. 8) Compression-

40. 9) Tablet coating-

41. Capsules-

43. Oral liquids-