Technology Transfer Pilot Plant scale up supac guidelines

1. Technology Transfer From R and D to Pilot Plant to
Plant for Non-Sterile Semisolids
Presented By: Guided By:
Mr. Shivshankar k chandapure Dr.Mr.Avinash R Tekade
M.pharm (semester-I) ( Professor & HOD Of
….Pharmaceutics Pharmaceutics)
Marathwada Mitra Mandal's College of
Pharmacy

2. Contents
 Introduction to technology transfer
 Importance of technology transfer
 Pilot plant
 Scale up of semisolid
 SUPAC guidelines
 Case study
 References

3. Technology transfer
Introduction:
 A process of successful progress from drug
discovery to product development,
clinical trials and finally to full scale
commercialization.
 Technology transfer is helpful to develop
dosage forms in various ways as it
provides efficiency in process, maintains
quality of product, helps to achieve
standardized process which facilitates

4. Importance of technology transfer in
pharmaceutical industry
 To elucidate necessary information to transfer
technology from R and D to actual manufacturing.
 It provide an opportunity to reduce cost on drug
discovery and development.
 It maintain quality of product and achieve
standardization process.
 Documented evidence of manufacturing process for drug
product.
 Technology transfer includes not only the patentable
aspects of production but also includes the business
processes, such as knowledge and skills.

5. Reasons for technology transfer
 Lack of manufacturing capacity.
 Lack of resources
 Lack of marketing and distribution
capability
 Exploitation in a different field of
application:

7. Pilot plant
 A pilot plant can be defined as the pre-commercial
production system which includes new production
technology and produces small volumes of new technology-
based products.
Pilot plant includes following:
 Development,
 Early development activities,
 Clinical supply manufacture,
 Technology evaluation
 Scale up and Transfer to production site

8. Pilot plant scale up activities
The major activities takes place during scale up in early
development phase are;
 Technical aspects of process development,
 Technical aspects of scale up
 Organisation-Organisation responsibility
 Determination of responsibility of technology transfer
team.
 Technology transfer documentation.
 FDA pre-approval inspection preparation.

9. Objectives of scale up
 Avoidance of the problems associated with the
scale-up.
 Production and process controls guidelines
preparation.
 To identify the critical features of the process
 Preparation and providing of Master
Manufacturing Formula for manufacturing.
 Evaluation and Validation for process and
equipment.
 Examination of the formula to assess the batch
stability.

10. Significance of scale up
 Standardization of formulae.
 Review of range of relevant processing
equipment.
 Optimization and control of production rate.
 Information on infrastructure of equipment
during the scale up batches.
 Information of batches physical space required
for equipment.
 Identification of critical features to maintain
quality of a product.
 Appropriate records and reports to support

11. Semisolids
Introduction:
Pharmaceutical semisolid includes
Ointments,creams,pastes,gel and
rigid foams.
They contain one or more active
ingredients dissolved or uniformly
dispersed in suitable base or in any
suitable emulsifier,viscosity
increasing agents.

12. The following parameters are to be considered
during the scale up of semisolid products;
 Mixing speed.
 Mixing equipment (Could be able to move
semisolid mass from outside walls to the centre
and from bottom to top of the kettle).
 Motors (Drive mixing system with appropriate
handling system at its most viscous stage).
 Heating and cooling process.
 Component homogenization.
Manufacturing of Semisolids

13.  Product transfer.
 Addition of active ingredients.
 Working temperature range.
 Shear during handling and transfer from
manufacturing to holding tank to filling lines.
 Transfer pumps (Easily must move viscous
material without applying excessive shear and
free of entrapped air).
 Packaging and storage

14. Mixing equipment
 Planetary mixer has great function of
blending, shearing and dispersing, which
suits well in dispersing and blending of
materials in solid to solid, solid to liquid,
liquid to liquid. Planetary mixer is widely
used in chemical, food processing, drug
producing, construction materials and
light industries.

15. Homogenization process
 Homogenization is the process of
converting non-uniform mixture
to a colloidal state or a uniform
mixture. It is done by reducing
particle size of mixtures or
uniform dispersion of the
mixtures making the product
homogenous..

16. Colloidal mill
A colloid mill is a machine that
is used to reduce the particle
size of a solid in suspension in
a liquid, or to reduce the
droplet size in emulsions.
Colloid mills work on the rotor-
stator principle: a rotor turns at
high speeds

17. Transfer pumps for semisolids

18. SUPAC GUIDLINES
(scale up post approved changes)
 SUPAC represents the changes recommended by the US
FDA at the time of scale up or approval of NDA / ANDA.
 In the process of developing a new drug product, the
batch sizes used in the earliest human studies are small
and the size of the batches is gradually increased (Scale-
up).
 The scale-up process and the changes made after approval
in the composition, manufacturing
 Process, manufacturing equipment, and change of site
have become known as Scale-Up and Post approval
Changes, or SUPAC.

19. SUPAC guidline defines
 The level of changes – Minor, Moderate and
Major Changes.
 Test – Application test, in vitro dissolution and
in vivo
 Filing – Annual report, changes being effected
supplement and Prior Approval Supplement.
 The level of changes may impact on formulation
and quality performance in following levels;
 Level 1: unlikely to have detectable Impact.
 Level 2: could have significant impact.

20. These guidelines provide recommendations for
post approval changes in;
 The components or composition change,
 The site of manufacture change,
 The scale-up of manufacture change
 The manufacturing (process and equipment)
change.

21. Scale-Up of an Oil/Water Cream
Containing 40% Diethylene
Glycol Monoethy Ether
 Drug development and industrial pharmacy 26 (1), 71-77, 2000
 The purpose of this study was to scale up an oil/water (o/w) cream
formulation containing 40% diethylene glycol monoethyl ether (DGME),
developed via 300-g laboratory batches in a 25-2fractional factorial design, to
7-kg batch sizes in a Brogli-10 homogenizer. The o/w cream was
manufactured via a standard phase-inversion process in the Brogli-10
homogenizer. Partitioning studies of DGME were conducted in test tubes at
ambient temperature and after 24 hr at 70°C in a convection oven.
 Phase height was measured by vernier calipers. Microscopy studies of
excipients with and without treatment with water or a DGME/water mixture
were conducted with a Nikon microscope after equilibration at 35°C for 24 hr.
During creation of the 7-kg pilot-scale batches, congealed material was
observed between the sweep agitation blade and the discharge port, where
the Brogli-10 homogenizer is not temperature jacketed.

22.  Factors that increased the amount of congealed material were higher
temperatures during primary emulsification and longer cooling times.
Partitioning studies revealed that DGME resides in the aqueous external
phase of this formulation.
 Microscopy studies revealed that DGME in the external phase of this cream
has a profound impact on the solubility of certain solid, waxy excipients
(e.g., cetyl alcohol and polyoxyethylene-2-stearyl ether) at 35°C. From this
study, it appears that DGME resides in the external phase of the o/w cream.
 During manufacturing, it is hypothesized that the presence of DGME in the
external phase alters the solubility of certain solid, waxy excipients in the
formula such that they no longer primarily reside in the internal oil phase.
 On cooling, these materials precipitate or congeal in the external phase. The
fractional factorial experimental design at the 300-g laboratory scale did not
predict the issues encountered during scale-up. Differences between
laboratory scale and pilot plant scale that explain why this phenomenon was
not seen during laboratory scale are differences in cooling times,
nonjacketed or “cold spots” in the Brogli-10 homogenizer, and a low
proportion of congealed material in relation to the total batch size (<1.5%).

23. References
1) Leon Lachman,Herbert A.Liberman,:Industerial
pharmacy.Special Indian edition 2009 page no.681
2) Michael Levin,Pharmaceutical process scale up ,Second
edition ,volume 157
3) Roop K Khar, Farhan J Ahmad, A Vashishtha, S. Harder, GV
Buskirk, JV Battista. PilotPlant Scale-up and Production
Management. In: Roop K Khar, SP Vyas, Farhan J Ahmad,
Gaurav K Jain, Editors. Industrial Pharmacy. 4th edition. New
Delhi: CBS Publishers & Distributors Pvt Ltd, 2013. pp. 947-
1002.

24. 4) Dhobale AV, Mahale AM, Shirsat M, Pethkar S,
Chakote V. Recent Advances in Pilot Plant Scale Up
Techniques - A Review. Indo Am J Pharm Res 2018;
8(4): 1060-1068.
5) Mounica NVN, Sharmila RV, Anusha S, Evangeline
L, Nagabhushanam MV,Nagarjunareddy D, et al.
Scale up and Postapproval changes (SUPAC)
Guidance for Industry: A Regulatory note. Int J Drug
RegulAff 2017; 5(1): 13-19.
6)Shayne Cox Gad, Pharmaceutical Manufacturing
Handbook ,Publisher ;A John Wiley and Sons ;67-80.

25. THANK YOU