ddC: Buyers' Clubs Discontinue Sales After Potency Variations Found

On January 24, 1992, the U. S. Food and Drug Administration
visited three buyers' clubs -- PWA Health Group in New York,
Healing Alternatives Foundation in San Francisco, and PWA Fight
for Life in Fort Lauderdale, Florida -- and took samples of ddC
for analysis, after unconfirmed reports of variations in dosage
between capsules. On February 5 the FDA notified the New York
and San Francisco clubs that significant variations in potency
had been found, in lots number 119153 (New York) and 119153 and
1291125 (San Francisco). An independent test run by the
distributor also found unacceptable potency variations. Both
clubs stopped selling the ddC, sent their customers warning
letters as the FDA had suggested, and offered refunds.

The ddC in Fort Lauderdale, supplied by a different
distributor in the form of tablets, not capsules, had much less
variation. PWA Fight for Life (PWA Health Alliance) has only
limited supplies of this product, but is still making it
available.

Among persons with HIV, the greatest fear by far has been
that the treatment may become unavailable. There is also a
demand that better quality-assurance testing be in place in the
future, with test results made available to clients.

The FDA asked buyers' clubs to "strongly encourage your
customers who wish to take ddC to explore the options for
obtaining legally produced ddC through the existing expanded
access program or on-going controlled clinical trials." However,
these options have not been available in the recent past; the
expanded access program referred to, for example, has not allowed
ddC to be combined with AZT, although almost all the current
interest in ddC is in its use as part of this combination, not in
single therapy with ddC alone. And of the two clinical trials
testing the ddC plus AZT combination in comparison with other
treatments, one (ACTG 155) is already full, and another (ACTG
175) is only beginning now. The FDA is working with the drug's
developer, Hoffmann-La Roche, to liberalize the company's
existing expanded access program to provide an alternative to
buyers' club ddC to some of the patients who are not eligible to
receive the drug in trials. We do not know how inclusive a
program, if any, will be worked out.

Future availability of combination treatment with ddC plus
AZT is not guaranteed; the AIDS community may need to defend this
treatment access in the future.

ddC Quality-Control Problem: What Was Found?

A recent letter from the PWA Health Group, the buyers' club
in New York, to its clients summarized the test results on that
group's ddC:

"The results of FDA laboratory testing indicated that ddC
obtained through the PWA Health Group varied in potency from
64-188 percent of declared value. That means that the
capsules tested (they tested 10), which should have
contained 0.25 mg of ddC, were found to contain between 0.16
and 0.47 mg of ddC. The average potency was found to be 129
percent of declared value, or approximately 0.32 mg."

In San Francisco, of ten individual capsules tested from
each of the two lots (20 capsules altogether), the FDA found no
ddC in one capsule, and 2.3 times the stated amount in another;
the other 18 varied between .25 and 1.28 times the stated amount.

In Fort Lauderdale, the ddC was provided in 0.50 mg tablets
(instead of 0.25 mg capsules); the tablets were made by a
different manufacturer. These tablets were found to contain from
86-91 percent of their declared value.

There is no evidence of any problem with the ddC itself,
although FDA tests are continuing; the variation seems to have
been in mixing it with an inert ingredient for filling the
capsules. (In any case, the danger of impurities from the
manufacture of the chemical would be less with ddC than with most
other drugs, because ddC is used in very small doses; one gram is
enough to treat an adult for well over a year.)

The dosage problem appears to be new, apparently brought on
by an attempt to improve the inert ingredient used as filler in
the capsules (by using a hypoallergenic filler). Earlier tests
on capsules from the same distributor, in December 1990, March
1991, and December 1991, showed much better product consistency.

Where Do We Go from Here?

The big fear in the AIDS community now is that ddC may be
unavailable, with people unable to get the treatment which they
and their physicians want, and which in many cases has worked
well for them. The best way to prevent this from happening would
be for the FDA to approve ddC -- and in the meantime for
developer Hoffmann-La Roche to liberalize its current "expanded
access" program to make ddC available to those who want to use it
in combination with AZT.

In addition, the buyers' clubs must tighten their quality
assurance procedures. A simple requirement that a report of the
results of quality-assurance testing be on file for every lot
before that lot is sold -- with copies available for any customer
who wants one -- would have prevented the current situation from
happening. In some cases, the clubs should do their own quality
control, independent of that of the distributor. Buyers' clubs
from across the country were already developing such guidelines
and standards, even before the ddC problem was suspected.

Because of the strong emotions raised by the fear that ddC
will be cut off, there have been suspicions that the timing of
this issue was part of a plot, by pharmaceutical companies, the
FDA, or others, to discredit and ultimately destroy the buyers'
clubs. We have found no evidence, or even any reason to believe,
that this is the case. Since thousands of people have been using
the buyers' club ddC (some for well over a year), usually on the
recommendation of their physician, the quality-assurance problem
would have come to light on its own, without any conspiracy.
This is because many physicians have naturally been concerned
that the drug their patients were using was of good quality;
during the last year physicians have tried to get samples
analyzed, either by Hoffmann-La Roche or by the FDA. We do not
know what tests were done. But once a problem was found, it
would have been grossly improper to conceal it and not give a
warning. So far at least it appears that the FDA, and Hoffmann-
La Roche (if it has been involved at all), have acted properly.

Among those close to the buyers' clubs, many believe that
private conflicts among a few AIDS activists have complicated the
handling of this situation, and also complicated other aspects of
the relationship between the clubs and the FDA. These disputes
would not have affected the quality-control problem itself,
however, or the timing of its discovery.

There is also a concern that the current, easily correctable
ddC dosage problem may later be used, by the FDA and/or
pharmaceutical companies, as an occasion to shut down access to
treatments which should be available.

The AIDS community may need to fight for ddC access in the
future -- either for FDA approval as soon as possible (the best
option), a liberalized expanded-access program (second best),
and/or for reliable buyers' club access. If all of these
channels are blocked, then the drug will be available in the
least desirable way -- through a traditional black market, where
money talks and the community has little control. Those with
financial means and/or connections will continue to get
treatment, but access could become difficult and burdensome for
others.