FDA fights ‘dishonest actors’ to preserve clinical potential of stem cell research

The FDA is increasing its stem cell therapy enforcement activity to diminish the influence of “unscrupulous actors” while protecting the promise of responsible stem cell therapy innovations. According to FDA Commissioner Scott Gottlieb, the agency plans to release a new comprehensive policy framework in the fall of 2017 to properly describe the rules governing the new field of regenerative stem cell research and product development. The framework will provide a more efficient means for stem cell product developers to gain FDA approval.

Enforcement

The announcement of stepped up enforcement activities follows a warning letter issued by the FDA on August 24, 2017 to US Stem Cell Clinic of Sunrise, Florida, due to the manufacturers “significant deviations from current good manufacturing practice requirements” and the seizure, on August 25, 2017, of an unapproved vaccine, which the California Stem Cell Treatment Centers in Rancho Mirage and Beverly Hills, California were using to create an unapproved stem cell product for cancer patients. The warning letter followed an investigation which revealed the clinic failed to develop appropriate procedures to prevent microbiological contamination. The seizure of the vaccine followed an inspection which revealed the vaccine was used to create an intravenous stem cell cancer product with unproven efficacy and risks of serious health problems related to using the virus.

Guidance

In response to the recent enforcement measures, the FDA launched a new working group focused on pursuing similar, “unscrupulous clinics.” The new framework develops a bright line to accommodate what Gottlieb called “good actors working on genuine science.” The FDA plans to set out the policy in a series of guidance documents.

Compounding pharmacy enjoined from manufacturing until remedial measures are implemented

Isomeric Pharmacy Solutions LLC (Isomeric) and three executives are permanently enjoined from manufacturing and distributing drugs considered adulterated in violation of the federal Food, Drug and Cosmetic Act (FDC Act) (21 U.S.C. §301 et seq.). The injunction was entered in the Utah district court following a complaint entered by the Department of Justice (DOJ) after finding that Isomeric, a compounding pharmacy, was producing drugs under insanitary conditions.

Isomeric

Isomeric manufactures, labels, and distributes drugs, particularly injectable hormones and corticosteroids, as well as ophthalmic drops. Most of the drugs are directly distributed to physicians. The company initiated three recalls in 2016 involving three types of injectable drugs. In April 2017, Isomeric recalled all lots of non-expired drug products that should have been sterile and were compounded between October 4, 2016 and February 7, 2017.

Complaint

According to the complaint, the FDA found that Isomeric repeatedly found several types of microorganisms in the air and on surfaces that should have been sterile. Products that were manufactured in these areas were prepared in insanitary conditions. The FDA found that Isomeric deviated from current good manufacturing practice requirements, and failed to thoroughly review discrepancies or failures found in batches of drugs.

The injunction was entered through a consent decree as part of a settlement. Isomeric and its chief executive officer, chief sales officer, and chief operating officer will not resume manufacturing, holding, or distributing drugs until proper remedial measures have been taken.

FDA warns Hospira to clear up flaws in injectable manufacturing

The FDA sent a letter warning Hospira Inc., a Pfizer Company, that some of the manufacturer’s drugs are adulterated due to violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. Following an FDA inspection, the agency identified a number of CGMP failures, including a lack of adequate controls, the presence of visible particulates in sterile injectable products, and inadequate procedures to prevent contamination. The FDA noted that the failure to promptly correct the identified violations could result in seizure and injunction.

The FDA inspected Hospira’s McPherson, Kansas, facility from May 16 to June 8, 2016. The inspection revealed violations of the federal Food, Drug, and Cosmetic Act (FDC Act) (21 U.S.C. § 351(a)(2)(B)), as well as federal regulations (21 C.F.R. parts 210 and 211). Some of the violations stemmed from inadequate investigation, including multiple instances where Hospira determined that visible particulate in sterile injectable products were pieces of cardboard but closed the investigations without taking further corrective action. The inspection also identified poor aseptic technique due to the use of unsterilized materials in an aseptic manufacturing environment. The FDA also determined that Hospira failed to submit field alert reports to the agency after the manufacturer identified numerous cases of extensive label deterioration.

An announcement by Momenta Pharmaceuticals, Inc. indicates the company’s position that the warning letter should not impact the production of Momenta’s Glatopa™ 20 mg (glatiramer acetate injection) product, which is filled and finished by Pfizer. However, Momenta’s Glatopa 40 mg abbreviated new drug application (ANDA), which is still under FDA review, is dependent on the “satisfactory resolution of the compliance observations at the Pfizer facility used to make the final product.” As a result, Momenta indicated that approval in the first quarter of 2017 is unlikely.

Fishy manufacturer shut down until it literally cleans up shop

An Alabama district court has permanently enjoined a seafood manufacturer from distributing adulterated and misbranded seafood products. The Department of Justice (DOJ), at the FDA’s request, filed a complaint alleging that BEK Catering LLC d/b/a Floppers Foods LLC and its owners caused food to be held under insanitary conditions. The injunction prevents the company and its owners from processing, packing, and holding fish or fishery products.

Inspection and complaint

In 2015, the FDA found that the company failed to control the risk of the growth of three different types of bacteria, and did not have adequate control over hazards that could be created by allergens and additives. The bacteria found during the inspection can cause foodborne illness, botulism, and listeriosis. The complaint noted that five different inspections beginning in 2011 revealed insanitary conditions and repeated regulatory violations.

Consent decree

The consent decree requires the company and its owners to cease operations beyond those incidental to product transport and delivery. In order to resume operations, they must notify the FDA 90 days in advance, comply with a set of remedial measures, and undergo inspection. The remedial measures include hiring an expert to ensure that operations conform with seafood hazard analysis critical control point (HACCP) and current good manufacturing practice (cGMP) regulations, all deficiencies are addressed, an employee training program is developed, and the FDA approves all changes.