FDA issues warning letters to makers of caffeinated alcoholic beverages

The FDA today issued warning letters to four companies that make caffeinated alcoholic beverages.  This came nearly a year after the agency asked 30 manufacturers to provide their rationale, and supporting data and information, for concluding that their use of caffeine in an alcoholic beverage is GRAS (generally recognized as safe) or prior sanctioned.

“FDA does not find support for the claim that the addition of caffeine to these  alcoholic beverages is ‘generally recognized as safe,’ which is the legal standard,” said Dr. Joshua M. Sharfstein, Principal Deputy Commissioner.  “To the contrary, there is evidence that the combinations of caffeine and alcohol in these products pose a public health concern.”

According to the FDA, its action follows a scientific review by the Agency.  FDA examined the published peer-reviewed literature on the co-consumption of caffeine and alcohol, consulted with experts in the fields of toxicology, neuropharmacology, emergency medicine, and epidemiology, and reviewed information provided by product manufacturers.  FDA also performed its own independent laboratory analysis of these products.

Although the warning letters were sent to only four companies who did not respond to the agency's letter last year that asked for the safety data, it appears that the agency is on the path to ban all caffeinated alcoholic beverages.

Latest regulatory trends from RAPS conference

There were several excellent speakers at the RPAS (Regulatory Affairs Professionals Society) annual conference in San Jose last week.  They represented regulatory professionals in the private and public sectors, both domestically and abroad.  Here are some of the take-away messages from the speakers:

• FDA is stepping up enforcement.  This shouldn't come as a surprise if you've been following the agency's enforcement actions lately.  In his speech to the food and dietary supplement industry, FDA's Chief Counsel Ralph S. Tyler stated that the agency has just began its enforcement efforts and that more are yet to come.  Among the areas of concern are the good manufacturing practices (GMP) regulations for dietary supplement products, as well as the notification requirements for new dietary ingredients.  The agency also intends to hold individual more accountable for violations, which would result in more criminal prosecutions of company executives and even employees.
• FTC is stepping up enforcement.  Similarly, the FTC is stepping up enforcement in the area of claim substantiation.  The FTC will be looking at scientific data more closely to determine whether they support claims made about a product.   Companies should pay more attention to testimonials, because according to the government, they are never substantiated. 
• Companies are very interested in the Chinese market, but are frustrated by the regulatory framework there.  Among the conference speakers were five officials from the Chinese State FDA (SFDA), who provided an overview of the medical device approval process in China.  This presentation was one of the popular ones at the conference, and the numbers and types of the questions asked at the end of the presentation showed many companies (large and small) are very interested in the Chinese market, and yet are frustrated with the lack of transparency in the approval process.  Here are some of the policies that can cause frustration:
• According to a SFDA official, if a foreign company manufactures a medical device in China, the company will have to export the finished product out of China.  However, if a Chinese company puts its own label on the same product, it will be able to sell the device in China.  This policy seems to have little to do with safety and efficacy.  
• Also according to the same official, a medical device imported into China will not receive SFDA approval if the device has not received market approval in the country of origin.  The message seemed to be: if this device is not good for your country, it's not good enough for China.
• Questions were asked about whether the SFDA would accept data from clinical trials done outside of the China.  The answer was as clear as water - generally no, but we will decide on a case by case basis, but if we decided you need to do more clinical trials, you need to conduct them in China.  
• Questions were asked about whether the SFDA would meet with companies to discuss their products before the companies submit their applications for approval of their products.  The answer was that the SFDA holds a "open forum" every Thursday during which anyone can participate in a Q&A session with the agency to discuss any regulatory issues.  According to the SFDA official, no appointment is required and people can participate by phone.  So much for confidentiality. 

I am still reviewing my notes and materials from the conference, and plan to blog about other interesting topics I ran across there.

RAPS Annual Conference & Exhibition, October 24-27, San Jose, CA

I will be at the RAPS annual conference next week, and look forward to hearing more about the latest developments in the regulatory world and establishing professional contacts.  I will try to post interesting topics and discussions at the conference. 

Caffeine and Alcohol, conventional mix or beverage from hell?

Last November, the FDA notified nearly 30 manufacturers of alcoholic beverages containing added caffeine that it intends to look into the safety and legality of their products.  The FDA requested that each manufacturer provide its rationale, and supporting data and information, for concluding that its use of caffeine in an alcoholic beverage is GRAS (generally recognized as safe) or prior sanctioned, within 30 days of the notice.

The Pittsburgh Post-Gazette published a follow-up report on the FDA's inquiry today.  Nearly a year later, 19 of the 27 companies have responded, including some who asked for more time.  Apparently, the FDA is still evaluating this issue "as quickly as possible" but "a decision regarding the use of caffeine in alcoholic beverages could take some time."

An ingredient added to food (other than dietary supplements) is a food additive, which requires pre-market approval based on data demonstrating safety submitted to the agency in a food additive petition.  However, a substance is exempt from the definition of a food additive (and exempt from pre-market approval) if it is GRAS. 

For a particular use of a substance to be GRAS, there must be both (1) evidence of safety, and (2) a basis to conclude that this evidence is generally known and accepted by qualified experts. 

Doctors and state attorney generals have presented their "anti-GRAS" studies showing that those who use caffeinated alcohol beverages drink more often, binge drink more often and are more likely to engage in risky behavior such as driving with a drunk driver.

It would be interesting to see the outcome of this case as well as the basis of these manufactures' GRAS determination, if any.  Rum and Coke, anyone?

The Fed took action against unapproved "drug" manufacturer

The federal government has barred a Montana company from the manufacture and sale of unapproved new drugs and dietary supplements, the FDA announced this week.  The order came in the form of a consent decree, filed in U.S. District Court for the District of Montana Wednesday and subject to court approval.

According to the FDA, the company manufactured and distributed a variety of unapproved new drugs that "were ineffective in treating the diseases they claim to treat."

The products - sold under such names as Black Salve, Cancema and Can-Support -- included topical salves purported to treat skin cancer, and oils and capsules to combat "serious diseases such as breast cancer, asthma, anemia and epilepsy," according to the FDA.

The FDA characterized many of these products as dietary supplements.
"The FDA will not tolerate unsubstantiated health or disease claims that may mislead customers," Autor said. "The FDA is committed to ensuring that consumers do not become victims of false cures."

In signing the consent decree, the company agreed to stop making and selling unapproved new drugs and products with unauthorized health claims and to hire an independent expert to review claims made for any future products, according to the statement.

Had the company hired an independent expert to review claims made for their products before they put them on the market, I suspect they would not have ended up in such deep trouble.

Knee device should not have been cleared, says FDA

In a press release released by the FDA today, the agency announced that an orthopedic device used in the knee should not have been cleared for marketing in the United States.

According to the FDA, a scientific re-evaluation of the device was conducted because records from the original review was not adequate to "dispel questions about the role of outside pressures on the review process."

The timing of this press release is interesting because the FDA is currently re-evaluating its medical device clearance process to see if it needs to be improved to ensure the safety and effectiveness of medical devices marketed in the U.S.  Proponents of the change have argued that the current review process is not transparent enough and is susceptible to outside influences.  The finding by the FDA about the orthopedic device appears to support that assertion.

First clinical trial with human embryonic stem cell began

Geron announced yesterday that it has began the first clinical trial of human embryonic stem cells.  The primary objective of this Phase I study is to assess the safety and tolerability of the stem cells.  However, instead of using healthy objects like in a typical Phase I trial, this study is conducted with patients who have suffered from what's called a complete thoracic spinal cord injury.

According to CNN, the FDA first approved the trial in January 2009, but later required further research before the study could proceed.  The FDA gave final approval in July of this year.

Stem cells are cells that have the ability to divide and develop into many different cell types in the body during early life and growth.  When a stem cell divides, each new cell has the potential either to remain a stem cell or to become another type of cell with a more specialized function, such as a nerve cell, a skin cell, or a red blood cell.

Information about the trial is thin on the FDA's website, as expected.  However, the FDA did publish this PowerPoint presentation, which shed some light on the safety issues the agency was focusing on.  Among them is the ability to predict inappropriate differentiation / tumorigenicity of the injected cells. 

As discussed stem cells can differentiate into different type of cells, including cancer cells.  Because we still don't know how the body regulates this differentiation process, it is not surprising that the FDA is particularly interested in how Geron would track the injected cells and monitor the differentiation process.