Regulatary Editor

FDA has extended until April 29 the comment period for the draft guidance for combination products the agency published in January, a document intended to offer more clarity on regulations for this class of products. The move was prompted at least in part by a request filed by the Combination Products Coalition (CPC; Washington) which petitioned the agency to add 30 days to the original March 30 deadline referenced in the accompanying Federal Register notice.

The draft guidance would supplant a 2004 guidance on combo product good manufacturing practices (GMPs) and offer more details as to how manufacturers could invoke drug and device GMPs in their product development efforts and their quality systems compliance frameworks. Former FDAer Dan Gottlieb of Epstein Becker Green (Washington) told Medical Device Daily that the draft, while useful in many regards, did not adequately take up the matter of design controls for legacy products, and that manufacturers would do well to have those design control documents and systems in place for subsequent FDA inspection (MDD, Feb. 4, 2015).

CPC's Feb. 13 letter to the docket makes note of "FDA's apparent sense of urgency" in originally allowing only 60 days to comment on the draft, but the letter also observes that design controls for combination products offer "one of the more complicated issues," given that a pharmaceutical agent embedded in a combination product are subject to Part 210 and Part 211. The docket remains open under docket number FDA-2015-D-0198.

TGA advises on Score knee system

The Therapeutic Goods Administration of Australia announced March 25 it and Amplitude Australia (Norwood, Australia) had issued an advisory regarding the use of the company's Score knee prosthesis. TGA said the use of the device with cementless fixation had produced a higher rate of revisions than expected when the patella is not resurfaced, but also that revisions were higher for cementless procedures than procedures using the Score device conducted with cemented fixation.

TGA said data from the National Joint Replacement Registry operated by the Australian Orthopaedic Association (Sydney, Australia) suggests that the revision rates for the Score system are "significantly higher for cases where no patella button is implanted at the time of primary surgery," with or without the use of fixation cement. However, other data indicate the Score system is less subject to revisions than other knee implants when a patella button is used. TGA noted further that the revision rate of cementless Score implants "when the patella button is used is not materially different than that of other implants."

Aetna passes on coverage of Nanostim

Leadless cardiac pacemakers are closing the gap with their implantable defibrillator cousins, but Aetna (Hartford, Connecticut) indicated in a recent clinical policy bulletin it is unimpressed with the data collected so far despite a positive review of one such device in Circulation.

Aetna said in a March 20 policy bulletin that the Nanostim, made by St. Jude Medical (St. Paul, Minnesota), and the Medtronic (Dublin, Ireland) Micra both still qualify as experimental/investigational "for arrhythmias and all other indications because of insufficient evidence of its safety and effectiveness." The key trial in the Aetna analysis appeared in Circulation March 24, 2014, and the authors, a group including Vivek Reddy of Mt. Sinai Hospital (New York) described the results of the Leadless study, a single-arm study of 33 patients followed to 90 days.

The study returned an overall complication-free rate of 94%, with one patient experiencing tamponade after device repositioning and hemodynamic collapse after device repositioning. This patient died at 18 days post-implant. The device ended up in the left ventricle in another patient despite placement in the apex, a situation created by the transition of the delivery catheter through an ovale. The device was retrieved and a new one implanted in the apex of the patient's right ventricle, but the authors acknowledged that the problem "could have led to an adverse outcome" had imaging not detected the issue.

The authors said that the complication-free rate of the Nanostim was comparable to that seen in pacemakers using leads, and that the absence of a separate pulse generator eliminates pocket erosion and pocket hematoma. The article pointed out that while the Nanostim is a single-chamber device, 20% of U.S. patients and 30% of patients in the European Union are implanted with single-chamber rather than dual-chamber units, a metric said to exceed 50% in some developing nations.

Aetna acknowledged that pacing performance had either improved or remained stable at three months, but indicated it preferred to see additional studies demonstrating safety, efficacy and stability before offering coverage. The next review will be in October 2016.

Aetna announced several other coverage policies in March 20 bulletins, including that flutemetamol F18-PET is experimental for Alzheimer's disease. The bulletin noted further that FDG-PET is experimental for adrenoleukodystrophy, splenomegaly, and multi-centric Castleman's disease.

The insurer noted that Clark et al (2011) evaluated whether florbetapir F 18 PET imaging conducted on live patients accurately predicts the presence of beta-amyloid formations at autopsy. While this and other studies answered the question in the affirmative, Aetna nonetheless held that a number of authors had drawn the conclusion that further study is required to "understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia."

Also among the batch of March 20 policy bulletins was one decreeing that cryoablation is experimental/investigational for treatment of abdominal wall endometriosis, pancreatic cancer, and tuberous sclerosis-associated renal angiomyolipoma. Aetna also addressed the use of endoluminal cryoablation for treatment of symptomatic varicose veins, deeming this use experimental and investigational as well.