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What’s ahead for pharmaceutical biotechnology ?

ELIZABETH  M.  TOPP,  PH.D.DANE  O.  K I LDS IG CHA IR  AND  DEPARTMENT  HEAD  DEPARTMENT OF   INDUSTR IAL  AND  PHYS ICAL  PHARMACY  PURDUE  UNIVERS ITY

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BIRS/SQA Summit on Regulatory ExcellencePurdue University, West Lafayette, INMay 18‐19, 2017

Cell‐based therapiesAND  DISTRIBUTED  MANUFACTURING

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3http://www.diamond.ac.uk/Home/News/LatestFeatures/02_09_15.html

4http://www.sciwri.club/archives/3115

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cGMP

Autologous vs. Allogenic 

Adapted from https://www.novartis.com

6Adapted from https://www.novartis.com

Local, distributed 

cGMP manufacturing ?

Dispensing ?

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7https://www.ucl.ac.uk/pharmacy/pharmacy‐news/print‐medshttp://medshadow.org/news/fda‐warns‐against‐tablet‐splitting‐save‐money/

BiosimilarsAND  ANALYTICAL  RESOLUTION  IN  QA/QC

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http://fineartamerica.com/featured/herceptin‐breast‐cancer‐drug‐dr‐mark‐j‐winter.html

http://fineartamerica.com/featured/herceptin‐breast‐cancer‐drug‐dr‐mark‐j‐winter.html

10S. Kozlowski et al., NEJM, 365/5: 385‐388, 2011

AspirinMW = 180 g/mol

Monoclonal antibodyMW = 150,000 g/mol

833x larger

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A generic drug is identical…to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use…chemically identical to [the] branded counterpart…

www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/understandinggenericdrugs/ucm144456.htm

Biosimilars are…highly similar to an already FDA‐approved biological product, known as the biological reference product … [and have] no clinically meaningful differences from the reference product.

www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm241718.htm

How (bio)similar is (bio)similar enough?

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Not different

Different

• Low resolution analytical methods

• Small sample number (n)

• Higher resolution analytical methods

• Larger sample number (n)

A statistics issue? 

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Which differences matter ?

Where do differences matter ?

Continuous ManufacturingAND  THE  MEANING  OF  “BATCH”

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http://www.pharmpro.com/articles/2011/08/continuous‐solid‐oral‐dosage‐processing

16http://xtalks.com/Continuous‐And‐Batch‐Manufacturing‐Pharmaceuticals.ashx

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Batch vs. continuousBATCH MANUFACTURING

Standard unit operations processing with limited process control

Off‐line testing after each unit operation and for final product

Regular cleaning and sterilization 

Familiar

Regulatory acceptability 

CONTINU0US MANUFACTURING

Smaller equipment and facilities, reduced capital cost

Process efficiency

Process flexibility

Shorter processing time

Reduced manual handling

In‐line monitoring

Closed loop process control

Real‐time release testing of finished product

17https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm341197.pdf

What’s a batch?

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21 CFR 210.3

Batch:  a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture

Lot: a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity

https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm341197.pdf

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19http://www.nicomac.com/granulation.html

20https://commons.wikimedia.org/wiki/File:Lyophilization_of_Pharmaceuticals_in_Vial.JPG

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Keeping UpRESOURCES FOR  YOUR  ONGOING  LEARNING

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22https://www.coursereport.com/resources/coding‐bootcamp‐vs‐college

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Colleges and academic units

Biotechnology Innovation and Regulatory Science

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$70 M federal$129 M state, industryTechnology innovationWorkforce development

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Re‐cap  Cell‐based therapies and distributed manufacturing

Biosimilars and analytical resolution

Continuous manufacturing and the meaning of “batch”

Keeping up and new types of education

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