Sorry About That Vaccine

[Guest guest]

Sorry About That Vaccine

By Gottlieb

Since May, patients prescribed the wonderful drug Enbrel for rheumatoid

arthritis have toted around a special card, to verify for their

pharmacist

that they were eligible to receive the newly-approved medicine.

Sounds like a methadone clinic, right? These tight checks, however,

aren't

performed because Enbrel is a controlled narcotic or an

experimental new

medicine. The drug is a monoclonal antibody, part of a

revolutionary new

class of compounds that must be specially crafted with designer

bacteria.

The drug's creator, Seattle-based Immunex, simply cannot make

enough of

it.

Poor planning? A fire on the Immunex production line? None of these.

As badly as the company wants to bring more manufacturing space

on line,

they have been hobbled by a morass of FDA regulations that

stretch months

into years. And because most small companies like Immunex can't

risk investing

in a $300 million manufacturing site years before their drugs

pass regulatory

muster, there are few facilities coming online anytime soon. The

result

is a worldwide shortage in manufacturing space for monoclonal

antibodies

and long waiting lists for Enbrel.

Americans want safeguards built into the process by which drugs and

vaccines

are manufactured. They don't want cockroaches crawling around

the fermentation

vats. But the process for certifying new manufacturing space has

become

so byzantine that it now takes a year to build a plant, then

three years to get it inspected and approved.

One reason is that calling the FDA is more akin to calling the phone

company than the fire department. Inspectors don't show up on

time. At

each of dozens of regulatory pauses, biotechnology companies

must stop

and bring in FDA inspection teams, who take weeks or even months

to come

on site.

The need to expand manufacturing space was the cover story when Health

and Human Services Secretary Tommy threatened to go to

Congress

to seek a generic version of the Anthrax-killing antibiotic

Cipro. In

that case, the threat was mostly to strong-arm Bayer into

lowering the

drug's price. But the pitch was believable, and the public

bought it.

Even the Canadians fretted that they didn't have enough

antibiotic stashed

away to respond to doomsday scenarios. We're lucky. Ramping up

production

in a bona fide crisis is no small task. There were already large

stores

of Cipro on the shelves.

Consider Bayer's response to mushrooming Cipro demand: converting a

facility

that formerly produced Baycol, a cholesterol-lowering drug that

(ironically)

was withdrawn by the FDA last month for an " unusually high "

number of side effects. The old Baycol facility has been turned

into a

Cipro factory. The FDA is crash-inspecting the new line, but

ramped-up

production will still take several months.

Similar issues are stalling the manufacture of an FDA-approved vaccine

for anthrax, manufactured by Michigan-based BioPort. The company

continues

a seven-year struggle with regulators to maintain manufacturing

compliance,

failing for everything from fans that are too small to a bug

found on

a laboratory floor.

Regulatory rules on vaccine production are also getting in the way of

preparations for a hypothetical smallpox attack. The government

plans

to rush inspection of new vaccine production lines, but it still

will

take almost a year. Secretary has received proposals

from ten

companies, all of which will have to prove quickly that they can

redirect

staff, equipment and facilities. In this case-with the watchful

eye of

the secretary fixed on their hides-FDA regulators have said they

can do

the approvals in months, instead of the usual years. They can do

it quickly-when

they need to.

BioPort has not been as lucky. It upgraded its anthrax-vaccine

manufacturing

space a half-dozen times. Since 1999, it has been given an

ever-expanding

list of required changes for the FDA to validate the plant. The

high cost

of regulatory compliance is one reason some major pharmaceutical

companies have left the vaccine business altogether. And why this season

there will

be a shortage of flu vaccine.

The future looks grim. In the case of monoclonal antibodies like Enbrel,

more than 200 companies are involved in developing approximately

twice

that number of antibodies, to treat a variety of human diseases.

When

other blockbuster drugs such as Enbrel or Neupogen-Amgen's new

drug to

help cancer patients fight infection-are added to those figures,

it is

clear the production crunch is just beginning.

Some manufacturers have been forced to bet the farm-literally-on an

alternative

manufacturing method called transgenics. Genzyme Transgenics,

Viragen

and CropTech are transferring human genes into goats, chickens

and tobacco

plants, in order to produce protein drugs more efficiently.

One bit of good news is that regulatory strictures have created new

industries

from scratch. Whole slates of companies, for example, specialize

in the

outsourced production of these drugs, freeing research-intensive

companies

from the risk of anticipating demand for experimental drugs that

may not be approved. But if demand suddenly takes off, even those

facilities may

not be enough to match demand.

Over-regulation of pharmaceutical manufacturing drives up the cost of

new medicines and keeps others off the production lines

altogether. If

the inspection process were not so slow and expensive, companies

would

be likelier to mothball spare production lines, anticipating

future demand.

And Washington might find the necessary capacity the next time

we have

an unexpected problem.

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