INDIAN PHARMACEUTICAL ASSOCIATION CONVENTION 5 … Bakshi - 7.pdf · indian pharmaceutical...

INDIAN PHARMACEUTICAL ASSOCIATION CONVENTION CONVENTION

5THAND 6TH JUNE 2015.

TRANFORMATION OF OSD MANUFACTURING

“ Right now, manufacturing experts from the 1950swould easily recognize the pharmaceutical

f i f d I i di d hmanufacturing processes of today. It is predicted thatmanufacturing will change in the next 25 years ascurrent manufacturing practices are abandoned in favorcurrent manufacturing practices are abandoned in favorof cleaner, flexible, more efficient continuousmanufacturing.”f g

Dr. Janet Woodcock,AAPS Annual meeting,October 2011.


Regulatory Definition of Batch: 21CFR 210.3“ A specific quantity of drug or other material that isi d d h if h d liintended to have uniform character and quality,within specified limits, and is produced according toa single manufacturing order during the same cyclea single manufacturing order during the same cycleof manufacture.”Batch refers to the quality of material and does notBatch refers to the quality of material and does notspecify the mode of manufacture.


Regulatory Definition of “Lot”: 21 CFR 210.3Lot ‐ a batch, or a specific identified portion of abatch having uniform character and quality withinbatch, having uniform character and quality withinspecified limits; or, in the case of a drug productproduced by continuous process, it is a specificidentified amount produced in a unit of time orquantity in a manner that assures its having uniformcharacter and quality within specified limitscharacter and quality within specified limits.Definitions for both “batch” and “lot” are applicableto continuous processes also.


h fThe vision of continuousmanufacturing is of anindustry with processesthat are integratedthat are integrated,based on a systemsapproach, having model‐based control andbased control, andmaking use of flow.Thus, seeing as acontinuousmanufacturing process.


Continuous manufacturing encompasses:Continuous manufacturing encompasses:Integration, a systems approach, flow, and model‐basedcontrol.Fewer partitions and few to no hallways as equipment will beFewer partitions and few to no hallways, as equipment will beplaced in larger areas where it can be engaged for a particularprocesses.Proper protective equipment would be used in a givenp p q p glocation to separate different product safety classes.Main production floor would consist of only equipment andpiping with pharmaceutical materials never exposed to theatmosphere.Cleaning could be performed without opening theequipment.


Apart from saving time and costs, continuous manufacturing canApart from saving time and costs, continuous manufacturing candramatically reduce building, energy and carbon footprints.An oral solid dose continuous manufacturing unit occupies drastically lessspace that is just what is needed for traditional batch process equipment.space that is just what is needed for traditional batch process equipment.The continuous tablet making unit can be easily fitted into a existing area.Less waste and more recovery, mean that continuous manufacturingoffers the opportunity to increase their sustainability by delivering moreoffers the opportunity to increase their sustainability by delivering moreenergy‐efficient operations.Reduction of process steps, smaller footprint, smaller equipment, andhigher product quality all leading to cost savings reduced risk of producthigher product quality, all leading to cost savings, reduced risk of productfailure and stock‐outs, and in the end, better pharmaceuticals for patients.The number of “correction” steps can be reduced or eliminated.No Scale up issues and minimal documentation requirementNo Scale up issues and minimal documentation requirement.


A batch is defined as a fspecific amount

produced in a unit of time (e.g., a day) or quantity (e gquantity (e.g., kilograms or a tablet count) that has uniform characteristics within specified limits. The batch definition h ld llshould allow traceability in case of a recall.


Environmental Need large manufacturing areas, different rooms for the

Economical Energy costs.

different rooms for the equipment used. May need areas for different sizes of the same equipment or need a

Cleaning costs. Cost of maintaining in‐doors environment. of the same equipment or need a

storage area. The equipment are shared between different processes –

Efforts to maintain pressure differences between areas. Cost of storage of equipment.between different processes –

requiring cleaning. May produce more product than needed

Cost of storage of equipment. Cost of products stored.

needed.


Introducing


IPC based completely automated recipe management and process p g pcontrol


HSMG Wet Cone mill

FBE PTS

Dry Cone Blender Bin

millBlender Bin

Blender To Compressionp


High Shear Granulation:g◦ Hot Melt Extrusion◦ Roll Compaction

Low Shear Granulation:◦ Top Spray granulation in FBE◦ Top Spray granulation in FBE


“Hot‐melt extrusion (HME) is one type of continuous processing technology thatHot melt extrusion (HME) is one type of continuous processing technology thathas been embraced over the past decade, HME is a “battle‐hardened,” proventechnology that has been used for 50 years in other industries. The challenge forthe pharmaceutical industry is to learn this existing technology and apply its well‐known processing principles to pharmaceutical processing”p g p p p p g


“ Fine powder can beFine powder can beprocessed intodensified sheets bythe use of mechanicalthe use of mechanicalpressure exerted ontwo counter rotatingcompaction rolls, thedensified sheets canthen be granulated tothen be granulated toany desired meshsize.”


The technology can beThe technology can be used for continuous granulation of powder.Top spray granulationTop spray granulation enhances the uniformity in granules profile.This technology alsoThis technology also improves the productivity with simultaneous drying y gprocess with granulation.


PRINICIPLE OF MECHANISM : SPATIAL FREQUENCY FILTER

Majority will be in‐line or on‐line methods, that do not require sample preparation. In‐line methods monitor the process as it is occurring, and the sample is not removed from the process stream. On‐line methods – a sample is diverted from the manufacturing process but may returned. Near line – sample is taken to an analytical instrument located near process line. Off‐line – remote lab, current system


PROCESS ANALYTICAL TECHNIQUE:

Data collected at dry mixing stage shows large number offines.Due to the high spray rate of binder addition, a sudden sharpincrease in particle size (granules) is seen at that stageincrease in particle size (granules) is seen at that stage.At the start of the dry mixing process D10, D50 and D90values were noted as 122.3, 185.3 and 402.5 micronsrespectively.At the end of granulation, D10, D50 and D90 values wereobserved to be 137 6 204 8 and 838 3 microns respectively


observed to be 137.6, 204.8 and 838.3 microns respectively.

Volumes Batch Continuous

< 500 M tablets/Yr + ‐

500 – 2000 M Tablets/Yr 0 0

> 2,000 M Tabs/Yr ‐ +

Multi Products + ‐

Single Product ‐ +

High Value + ‐

High Potency ‐ +

Difficult Rheology ‐ +gy

Explosivity ‐ +

Seasonal + ‐

Existing Product + ‐g

Portability ‐ +

Active Coating + ‐

Multi ‐ Layer + ‐


y

Technology Observations

CONTINUOUS BLENDING/ MIXING

Multiple Technologies• Rotary Drums• Double Helical ribbon blenders• Double Auger• Zig Zag

• Capacities grams to metric tonnes per hr• Shaft seals may be a concern• Complex arrangements may be a challenge for cleaning

Zig Zag• Vibrating Rotating Pads

GRANULATION AND DRYING

Continuous Wet GranulationContinuous Extruders

• Wide range of capacities• Wide range of screw designsContinuous Extruders

• Hot Melt Extruder• Wide range of screw designs• Multiple feed ports required per ingredient• Thermal control required along length of unit• Cleanability concerns

DRYGRANULATIONDRYGRANULATION

• Roller Compactors • Established technology• Wide range capacities• Thermal control required in some instances


Technology Observations

CONTINUOUS DRYERS

• Vertical fluid bed dryers• Horizontal Fluid bed dryers

• Wide range of capacities• CIP and containment capabilities• Explosion risk• Explosion risk• Segmentalised for testing

TABLET PRESSES

Tablet Presses • Established technologyLi i d f i i• Limited range of capacities

• CIP and containment capabilities• True continuous inprocess testing is not available

CONTINUOUS COATING

• Coaters • Technology has been available for other industries• Very high capacities with limited turn down• Sequential start, stop and stand by• Multiple gun adjustments and controls• Inclining pan for full discharge• Capacity to switch to batch• Capacity to switch to batch


References:h f i◦ www.pharmamanufacturing.com

◦ USFDA◦ www.aaps.orgp g◦ Continuous Manufacturing of Pharmaceuticals symposium


The opportunities are there and an experiencedintegrator is here who canmake it happenintegrator is here who canmake it happen…….


INDIAN PHARMACEUTICAL ASSOCIATION CONVENTION 5 … Bakshi - 7.pdf · indian pharmaceutical...

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