WHEELING, W.Va., July 17 — Two lots of generic propofol vials have been recalled by Teva Pharmaceuticals because of contamination with bacterial endotoxin.

The announcement quickly prompted questions as to whether the contaminated propofol might have played a role in music legend Michael Jackson’s death last month, but a Teva suggested it didn’t.

Propofol vials manufactured by Teva were found in Jackson’s home. (See Propofol Found in Jackson’s Home)

A Teva spokeswoman said the company had been contacted by the Drug Enforcement Administration about a lot number on a specific propofol vial “in relation to an investigation they are conducting,” which she did not confirm or deny involved the Jackson death.

That lot number, she said, is not one of those involved in the recall.

The recall involves lot numbers 31305429B and 31305430B. Providers and pharmacies with vials from these lots should stop using them and return them to the distributor.

Teva said it had been notified of 41 propofol-treated patients who experienced postoperative fever, chills, and other flu-like symptoms.

“Based on available information it appears that all febrile or flu-like reactions were self-limiting with spontaneous resolution,” according to the firm’s announcement.

Federal investigators said the cases were in Florida, Missouri, and Arizona.

The Teva spokeswoman said the firm sold the lots to a distributor and had no knowledge of where the drug vials may have been shipped after that.

She said the company did not yet know how the contamination occurred. An investigation is ongoing.

Although the adverse effects reported so far have been mild, exposure to endotoxin contamination could lead to acute respiratory distress syndrome, shock, and death — fueling the speculation about a connection to Jackson’s death.

The Los Angeles County coroner’s office has not yet released its autopsy report on the pop singer, who died June 25 after collapsing in his home.

Related source:

• Teva’s recall notice

Related Article(s):

• Propofol Found in Jackson’s Home

LATITUDE Pharmaceuticals, Inc. (LPI), a San Diego-based drug formulation developer, announced today that it has initiated two new collaboration programs for its Phospholipid Gel (PG) Depot drug delivery platform. The programs are designed to provide prolonged and peak-free pharmacokinetic profiles for 3 and 7 days following a subcutaneous injection for an antibiotic and a protein drug, respectively. The new studies bring the total to seven feasibility/license agreements that are applying the PG Depot to deliver small molecules, peptides, and proteins for pain, metabolic disease, anti-bacterial, and cardiovascular applications.

Andrew Chen, PhD, LPI’s president, noted, “Our newest feasibility studies represent a growing validation of our PG Depot technology. Like our ongoing collaborations, the new programs aim to transform a cumbersome routine of multiple injections each day into a convenient once-daily or once-weekly format. Both pharma and biotech companies definitely see high value in simplifying parenteral drug administration and extending or resurrecting IP protection through novel delivery technology. The protein-friendly nature of the PG Depot will create many opportunities to convert biologics from daily to weekly injections.”

About PG Depot

LPI’s proprietary PG Depot technology is a versatile parenteral drug delivery platform for small molecules and biological therapeutics that delivers 1-7 days of low burst, peak-free sustained drug release following a subcutaneous or intramuscular injection. The PG Depot is provided as a single-phase, ready-to-use, self-administration-capable gel that is injectable through fine (27G or smaller) needles. The gel is compatible with hydrophilic and hydrophobic small molecule drugs as well as peptides and proteins and can be manufactured using conventional processes. Because it is composed of FDA-approved injectable and biodegradable ingredients, the PG Depot has key advantages over other depot systems, which use new polymers or animal-derived materials and face ever-increasing safety hurdles at the FDA and other regulatory agencies.

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LATITUDE Pharmaceuticals, Inc.

WHEELING, W.Va., July 17 — The FDA has clarified how it plans to regulate drug additives intended to thwart counterfeiting and make it easier for authorities, providers, and consumers to spot fake prescription drugs.

The agency issued a draft guidance to industry this week covering anticounterfeiting measures that legitimate manufacturers might use to authenticate their products.

In particular, it addresses so-called physical-chemical identifiers — unique, hard-to-duplicate, readily detected additives that would distinguish drugs made at approved facilities from cheap, unlicensed fakes — placed on or in pills and capsules.

The scale of counterfeiting in the U.S. is unknown, but drug manufacturers take it very seriously.

At a Washington seminar last month, a Pfizer security official said he was recently asked to authenticate a batch of products ostensibly produced by the company and shipped from overseas.

They were addressed to U.S. residents and had arrived at a mail facility over the course of a week.

Of 250 packages labeled as Viagra (the company’s formulation of sildenafil for erectile dysfunction), all turned out to be counterfeit, he said.

At the same seminar, an FDA enforcement official said the agency had opened 56 new counterfeiting investigations in 2008.

“Drug counterfeiting is a serious public health concern,” FDA Commissioner Margaret Hamburg, MD, said in announcing the guidance.

She said the agency wanted to work with industry “to help ensure that consumers are not exposed to products containing unknown, ineffective, or harmful ingredients.”

Much of the guidance is unsurprising, such as a recommendation that additives not be allergenic or used at unsafe levels.

The agency said it expects that manufacturers would generally prefer identifiers based on existing food additives or colorants, or on drug excipients with well-established safety profiles.

“To minimize toxicological risk, FDA recommends using permissible direct food additives, including those affirmed as generally recognized as safe or those ingredients listed in the FDA Inactive Ingredient Guide,” according to the guidance.

For additives considered unlikely to cause adverse effects in patients taking the drugs, companies may simply report the addition in an annual report rather than seek prior approval, the FDA said.

Companies will also be able to use their own discretion in deciding whether to list the identifiers as ingredients on the label.

Manufacturers might wish to do so when the identifier is visually obvious, the agency said, so that healthcare providers and patients know to look for it.

However, the guidance noted, such labeling changes will be subject to the FDA’s usual reporting and approval process.

In all cases, manufacturers will need to document the identifier’s chemical composition, how it will be incorporated in solid oral drugs, and at what concentration.

They will also need to verify that it doesn’t alter the drug’s biological behavior in any way.

Technically, the FDA’s guidance documents are merely suggestions, representing the agency’s “current thinking” on issues. But companies usually follow them closely.

The agency will take comments on the draft through Oct. 7, after which it will release a final version.