Bulletin Board of Oral Pathology

Forum for Clinical and Surgical Oral Pathology

Dear Colleagues:

Following the posting in January and subsequent discussion regarding the return of tetracycline to the United States commercial marketplace, I asked a long-time friend and physician who now works for a pharmaceutical company that happens to make tetracycline derivatives for some explanation or rationale of the spike in prices beyond simple capitalism.

He provided the following information that I thought would be of interest and worth sharing. 

Hello John,

Sorry for the delayed response, but here is what I have been able to piece together.

All of the tetracycline derivatives that are currently approved are manufactured by a semi-synthetic route;  the tetracyclic core shown below is produced by fermentation in large vats of Streptomyces spp and tetracycline is isolated from the growth medium.

For tetracycline derivatives such as doxycycline and minocycline, side chains are added to the left-hand part of the molecule.

In the past, it has been very cheap to produce tetracycline by fermentation and it was readily available.  However, within the past 5-10 years the following have occurred:

• Regulatory agencies (FDA in the US and EMA in Europe) have imposed increasingly stringent manufacturing requirements.  These were initially intended to cover biologics, but have also been applied to the older fermentation systems, increasing cost of production of tetracycline by approximately 100 fold
• The majority of manufacturing facilities have transferred from fermentation to the production of biologics where the profit margin is significantly higher
• Because of widespread tetracycline resistance, the demand for tetracycline as an antibiotic has markedly decreased – the majority of the tetracycline effects in dermatologic conditions are mediated by anti-inflammatory action of tetracyclines rather and antimicrobial activity

For these reasons, the majority of the manufacturing facilities that previously made tetracycline by fermentation, have stopped production, resulting in decreased supply which has led the shortage of doxycycline and the increasing prices.  There are a few older facilities still fermenting tetracycline and a couple of new ones have started production, but at increased costs.

I know that this doesn’t explain everything, but is what I have been able to discover so far. 

The teracyclines that we are developing are fully synthetic and no fermentation is required.

I will keep trying to find out more.

From: Kalmar, John 
Sent: Friday, January 31, 2014 4:57 PM
To: Bulletin Board of Oral Pathology (BBOPLIST@LISTSERV.BUFFALO.EDU)
Subject: tetracycline HCl returns

Dear Colleagues:

Some of you may have noticed this through recent dental advertising: tetracycline HCl (250 mg and 500 mg) has come back to the marketplace in the US through Heritage Pharmaceuticals, Eatontown, NJ.

While using the generic name, the company does not appear interested in generic pricing.  OSU pharmacy related that the pharmacy cost will be ~$400/100 of the 250 mg capsules and ~$800/100 of the 500 mg dose.   

Since the mark-up from pharmacy to consumer can be substantial (2-4 fold or more), it’s clear that even a small prescription could be surprisingly expensive for the unwary patient or uninformed prescriber.

For perspective, the cost to the patient for 120 tabs of generic tetracycline HCl 250 mg  (as reported by the same OSU pharmacy) back in March 2011 was $21.       

Have a good weekend.  And stay healthy.

John

John R. Kalmar, DMD, PhD
Associate Dean for Academic Affairs
Program Director, Oral and Maxillofacial Pathology
The Ohio State University College of Dentistry 
1159 Postle Hall, 305 W. 12th Avenue, Columbus, OH 43210-1267
614-292-4250 Office / 614-292-7619 Fax
kalmar.7@osu.edu http://dent.osu.edu

This electronic mail transmission contains confidential information intended only for the person(s) named. Any use, distribution, copying or disclosure is strictly prohibited. If you received this transmission in error, please notify the sender by reply e-mail and delete the message. Opinions, conclusions, and other information in this message that do not relate to the official business of The Ohio State University shall be understood to be neither construed nor endorsed by the university. When addressed to OSU patients, any information contained in this e-mail is subject to the terms and conditions governing patient care and privacy.