State

of the Industry
Liz Tierney, Publisher

Topics Covered
The Growth of Biologics and Temperature
Sensitive Packaging
FDA Global Shift from GMPs to Quality
PDA/FDA Joint Regulatory Conference
Serialization and beyond
.

Biologics
Estimated, global biologics market will be at
$221 billion by 2017
High value products diagnosing, treating, and
preventing chronic, life-threatening diseases
Expected to grow faster than overall pharma
market

Biologics
What is a biopharmaceutical?
aka biological medical product, biologic or biological
Any medicinal product manufactured in or extracted from
biological sourcesmanufactured in a living system
Microorganism
Plant cells
Animal cells

Biologics

Most biologics are very large, complex

molecules or a mixture of molecules
Many are manufactured using
recombinant DNA technology

Biologics

Biologics
Examples include:

Monoclonal antibodies
Vaccines/theraputic vaccines
Blood and blood products
Gene therapies
Cell therapies

Biologics
There are 907 biologics reported now in the
pipeline represent the cutting edge of
medicine.
They will be used to treat cancer, infectious
diseases, autoimmune disorders, etc.
Targeting 100 diseases--not only treat, but to
prevent or diagnose.

Biologics

Biologics
1/3 of new drug approvals in developed
markets have been biologics
Accounted for 6 of the 10 best selling drugs in
2015
Probability of clinical success is less than 12%

Biologics
Biologics offer major pharmaceutical
manufacturers built in patent protection.
The product is the process. Living systems can
be very sensitive to minor changes in the mfg
process and can change the way the biologic
functions

Biologics
So the sheer size of these APIs (active
pharmaceutical ingredients) are behemoths
when comparing their relative molecular mass
to even the largest of conventional drugs.
Highly unstable, susceptible to vibration, light
and temperature excursions.
The COLD Chain

Biologics
The Centers For Disease Control and Prevention
estimates that $300 million of vaccines alone
are destroyed due to improper storage and
distribution.
Numbers for other bio-therapeutics not known!
Figures include only product known or
suspected to be compromised.

Biologics
The Last Mile
An assessment of 721 primary care doctors
offices revealed 17 to 37 percent of staff
members had exposed their vaccine inventory to
improper conditions.

Biologics
Refrigerators set too warm or too cold
Placing vaccine in the refrigerator door
Placing food in same cooling unit
Leaving inventory out on table during group
vaccinations
Returning warm, unused doses to refrigerator

FDA Office of Quality

Ten years ago the FDA created a Vision for 21st
Century Manufacturing. The agency wanted an
efficient, flexible pharmaceutical manufacturing
sector producing high quality drugs without
extensive regulatory oversight.

FDA Office of Quality

So how are we doing a decade later?
tremendous increase in field alert reports.
Recalls have increased dramatically
Drug shortages increasing as well
Source: Russell Wesdyk, FDA Office of Pharmaceutical Science

FDA Office of Quality

Cancer patient on a pretty special drug.
Lets say complex and expensive to
manufacture. (Biologic?)
The plant is registering 50% of batches failing.
Does that sound like a validated process to
you? You start running into availability
issues.

FDA Office of Pharma Quality

FDA talking to industry to develop data that may
signal which manufacturing plants are straying
from standards and may need inspection.
The agency currently only collects such
information during inspections.
The thrust of the office is to head off potential
concerns before the agency wields penalties.

FDA Office of Quality

A question of resources.
Inspectors are often responsible for a wide variety
of facilities:

Food
Medical device
Pharmaceutical
Biologics

FDA Office of Quality

The focus for the FDA to act globally (FDASIA)

puts even more pressure on resources, making it
more imperative to make predictions about
where investigation would do most good, or
catch problems percolating under the surface.

FDA Office of Quality-Metrics

Whats FDASIA Looking For?
Lot acceptance/lot failure rates
Product quality complaint rate
Low acceptance rate for whole site
Confirmed out of spec rates
Recalls
Rework

FDA Office of Quality

Gaming The System

FDA Office of Quality

But certainly plants ranked high would not be
on a priority list to inspect up to ten years.
Huge incentive for well-run, top-tier
manufacturers to keep FDA out of their hair.
Concentrate on the bad actors.

FDA Office of Quality

How could patient groups or insurance
companies use this data?
Could you see a label by the pharmacy stating:
The medication you are about to take was
made at a plant rated 1,447 out of 5,000 plants
in quality.
What does that even mean?

FDA Office of Quality

From the same Bloomberg report
A fourth Ranbaxy facility was banned from U.S.
exports after FDA inspectors found drugs were
being retested to gain favorable results after
initial analysis failed.
Gaming the system, indeed.

FDASIA TAKES FDA GLOBAL

Regulatory Conference Update

Food And Drug Administration Safety and
Innovation Act. July 9, 2012
FDASIA includes a set of provisions, contained in
Title VII of the statute, which give FDA new
authority to address the challenges posed by an
increasingly global drug supply chain, including
shortages. FDA is working to implement these
authorities.

Regulatory Conference Update

Supply chain fun facts

300,000 foreign factories

150 different countries
130,000 regulated importers
Shipping to 300 U.S. ports

Regulatory Conference Update

50% of fruit
20% of vegetables
80% of seafood and spices
40% of drugs
80% of the APIs used to make drugs
Typical drug mfr. employs 35 contract mfrs
around the globe
No distinction between U.S. and foreign plant

Regulatory Conference Update

Drug Shortages
Between 150 and 200 drugs suffered from
acute shortages, a four-fold increase between
2005 and 2012.
2012FDA Safety and Innovation Act was
passed to help eliminate drug shortages
FDA helped prevent 681 drug shortages since
2012
In 2015, only 68 shortages thru end of June

Regulatory Conference Update

While reasons include raw materials shortages or
not enough manufacturing capacity, the number
one reason is product quality
problems at the manufacturing/processing stage
The FDA is looking to the continuous process
industries and asking, why can't we have the
same quality metrics?

Serialization
Since California Board of
Pharmacy set deadlines

Serialization

Serialization

Serialization

Serialization

Serialization

Serialization

Serialization

On The Frontier
Serialization IT and the Cloud, CMOs
Wearables and medical device cyber security
Clinical trial global supply chainorphan
drugs and cold storage and transport.
Surgical Robots and smart kitting

Thank You!
Sources
Pharmaceutical Research and Manufacturers of America
GxP Lifeline (A Master Control Publication)
Healthcare Packaging magazine
Pharmaceutical Manufacturing Magazine
Business Monitor International
PharmaManufacturing.com
Bio Industry Organization
Fisher BioServices
Bloomberg
Healthcare Packaging Magazine