The Quality Lowdown: Diversion, Cross-Contamination And PR Mix-Ups

McKesson meets with US FDA over opioid diversion warning letter, while UK MHRA takes risk-based approach to cross-contamination recalls and firm says it’s the other Guardian Pharmacy.

 

Earlier this month, US FDA disclosed that top officials from San Francisco-based distributor McKesson Corp. went to Washington and met with Commissioner Scott Gottlieb about the warning letter the firm received for failing to look into an opioid diversion issue.

Meanwhile, an interesting risk-based approach to cross-contamination risks came to light in which the UK regulatory authority suggests asking the manufacturer about the previous products it made at a facility in India.

The International Council on Harmonization is proceeding with efforts to appraise how well its new members are harmonizing their regulations, and its quality discussion group has grown quite large.

Risk management and much more is on the US FDA’s regulatory agenda for this year.

And bad publicity over one compounding pharmacy’s products that impaired patients’ vision has turned into a PR nightmare for another pharmacy of the same name and nearby location.

McKesson Brass Meet With Gottlieb Over Warning Letter

Brian Tyler, McKesson Corp.’s chief operating officer, and Lori Schechter, the pharmaceutical distributor’s general counsel and chief compliance officer, met with FDA Commissioner Scott Gottlieb March 6 to discuss a warning letter the agency sent the firm a month before.

The warning letter faulted McKesson for failing to respond appropriately to an opioid diversion case despite the firm’s responsibilities under the Drug Supply Chain Security Act. (Also see "FDA Warning Letter Hits Distributor McKesson For Allowing Diversion Of Opioids And Other Medications" - Pink Sheet, 12 Feb, 2019.)

The warning letter is based on inspections last summer at a McKesson distribution center in Wilsonville, Oregon, and at the firm’s San Francisco headquarters. Although FDA disclosed the fact of the meeting, the agency didn’t disclose what transpired there.

Catch Up With The Lowdown

The Pink Sheet's periodic Quality Lowdowns offer quick takes on manufacturing quality and compliance developments. Recent additions include:

• (Also see "The Quality Lowdown: Valsartan Options, Supply Chain Warnings, Button Cameras" - Pink Sheet, 18 Mar, 2019.)
• (Also see "The Post-Shutdown Quality Lowdown" - Pink Sheet, 3 Feb, 2019.)

Tyler is set to succeed John Hammergren as CEO April 1 after Hammergren retired.

The warning letter is the first concerning a violation of the Food Drug & Cosmetic Act provision at 21 CFR 582(c)(4), added by DSCSA to set forth the responsibilities of wholesale distributors to make sure they’re not sending counterfeit drugs to pharmacies.

Three Rite Aid pharmacies in Michigan said McKesson sent them bottles of oxycodone tablets that had been tampered with, most likely at a McKesson distribution center in Oregon. The opioids were missing and in their place were smaller amounts of over-the-counter pain relievers and antibiotics. But McKesson failed to respond to the reports, for example by quarantining and investigating suspect product.

Additionally,  the Albertsons store chain received illegitimate divalproex and losartan products from McKesson, and another pharmacy received a product labeled as Triumeq from McKesson that instead contained gemfibrozil.

Limited Cross-Contamination Recalls Urged For Micro Labs Plant

EU member states should take an unusual type of risk-based approach to recalling drug products based on cross-contamination control failures that the UK Medicines and Healthcare products Regulatory Agency identified during a Nov. 15, 2018 inspection of a Micro Labs Ltd. facility in Hosur, India, the agency said.

They should contact the site to find out if the products released to their markets had been manufactured at the site with granulation, blending or compression equipment following manufacture of low permitted-daily-exposure products in the same equipment. If so, they should consider recalls, MHRA said in a Jan. 24 EU GMP noncompliance notice. The notice applies to all batches not released to market, MHRA said.

One non-EU authority, the World Health Organization, said in a March 8 notice that it contacted the facility about potential risks associated with WHO-prequalified products on the market and concluded that a recall would not be necessary. However, WHO suggested that procurers and distributors of drug products manufactured at the Micro Labs facility may want to consider switching to alternative suppliers for specific products, depending on the risk.

ICH Implementation Assessment Underway

The International Council on Harmonization is moving ahead with assessing implementation of its guidelines by its rapidly growing cadre of regulatory members and observers.

The council is accepting responses this month to an implementation survey sent to members and observers in February, according to a summary report of its Jan. 30 management committee teleconference.

The group has added a page to its website on guidelines implementation that defines what implementation is and isn’t, as well as what adherence to ICH guidelines is and isn’t.

For now, adherence is for the regulators to judge. But eventually, they will have to consider industry’s view as well, according to a footnote in the definitions.

ICH Quality Discussion Group Swells To 31

After debating concerns about the size of the group, the International Council on Harmonization’s management committee agreed on its Jan. 30 teleconference to approve all 21 experts nominated for the Informal Quality Discussion Group the council is establishing. (Also see "ICH Aims For Drug Quality Standards That Promote Continual Improvement, New Technology" - Pink Sheet, 29 Nov, 2018.)

Risk Management On FDA’s 2019 Drug Quality Guidance Agenda

Risk management planning for drug manufacturing is on the agenda for pharmaceutical quality and chemistry, manufacturing and controls guidance at the US FDA for 2019.

There also is likely to be guidance on stability testing for new drugs, generics, biologics and active pharmaceutical ingredients, according to the guidance agenda FDA published earlier this month.

There will be guidance on using USP’s pending monograph process to harmonize compendial standards with drug application CMC approval requirements.

Look for guidance on quality in continuous manufacturing, in-vitro opioid abuse deterrence evaluation, and endotoxin limits for oncologic drugs and biologics.

There will also be advice regarding type V drug master file reference information on drugs combined with devices that involve electronics or software.

In addition, the agency plans to issue guidance related to specific dosage forms, including transdermals and topicals, topical ophthalmics, and on visible particulates in injectables.

The agenda includes some guidance documents that already have been issued, at least in draft, such as one on voluntary consensus standards. (Also see "FDA Proposes To Rely On Industry-Driven Consensus Quality Standards In New Drug Reviews " - Pink Sheet, 13 Feb, 2019.)

There will be some procedural guidance of interest to the manufacturing quality community. For example, there will be revised guidance on identifying distribution trading partners under the Drug Supply Chain Security Act – and guidance on notifying FDA about permanent manufacturing discontinuance or interruption.

The Other Guardian Pharmacy’s PR Nightmare

Publicity surrounding vision impairment of at least 43 patients injected during cataract surgery with a steroid and anti-infective compounded by a Dallas, Texas, pharmacy has been a public relations nightmare for another pharmacy of the same name, which also has a Dallas area location.

It was JMA Partners Inc. doing business as Guardian Pharmacy Services of Dallas that compounded the vision-impairing steroid/anti-infective with high levels of a surfactant that had never been approved for intravitreal use. (Also see "The Quality Lowdown: ICH Q13 and Q14, Gene Therapy CMC, Drug Shortage Gaps, And An Excipient Misstep" - Pink Sheet, 25 Jun, 2018.)

It certainly was not Guardian Pharmacy Services of Atlanta, a long-term care services pharmacy that recently acquired Pharmacy Concepts in Arlington, Texas, and renamed it as Guardian Pharmacy of Dallas-Fort Worth, a point the Atlanta-based firm’s PR agency, Cookerly, made clear in an email to the Pink Sheet following its report on the lodging of a consent decree concerning the Dallas pharmacy. (Also see "Guardian Pharmacy Ordered To Stop Making Sterile Drugs Under Terms Of Consent Decree " - Pink Sheet, 15 Mar, 2019.)

Cookerly asked for a “disclaimer” saying that “Guardian Pharmacy Services in Dallas is not affiliated with Guardian Pharmacy of Dallas-Fort Worth in Arlington, a member of the national long-term care Guardian Pharmacy Services headquartered in Atlanta.”

Recent Drug Recalls Of Note

Recalls of valsartan and similar blood pressure medications tainted with nitrosamines continued, but other issues also generated recalls over the past week.

Hospira Inc. March 15 recalled three lots of 8.4% sodium bicarbonate injection USP due to glass particulates.

Mylan Institutional March 18 recalled two lots of levoleucovorin injection it had distributed after copper salt particulates were discovered during 12-month stability testing. Alidac Pharmaceuticals Ltd. manufactured the lots.

Kingston Pharma LLC, Massena, New York, March 20 recalled one lot of oral liquid cough syrup distributed in Dollar General stores because of potential for contamination with Bacillus cereus and Bacillus circulans that came to light in audit testing.

Stokes Healthcare Inc. March 13 recalled one lot of pilocarpine 0.1% ophthalmic solution found to contain high levels of the preservative benzalkonium chloride.

Meanwhile, Legacy Pharmaceutical Packaging LLC March 15 and March 19 recalled losartan potassium tablets due to detection of a nitrosamine impurity in the active pharmaceutical ingredient.