Christine Blank

Shortages of vital generic drugs—particularly since the start of the coronavirus disease 2019 (COVID-19) pandemic in the US—are well known by pharmacy teams in both health systems and community settings.

And, although pharmacy associations appreciate the Trump administration’s efforts to move more pharmaceutical and active pharmaceutical ingredient (API) manufacturing to the United States via a recent executive order, they say government initiatives must include an overall plan for drug pricing, payment model, and supply chain transparency.

Since the start of COVID-19, the incredible demand for medications relating to patients being on ventilators—including sedatives, vasopressors, and neuromuscular blockers—led to several shortages. Fentanyl injection, midazolam injection, rocuronium injection, and propofol injection were among those that were most in short supply, according to Erin Fox, PharmD, senior director of drug information and support services at the University of Utah

However, the COVID-19-related shortages have largely been resolved, with the exception of neuromuscular blockers, ASHP Vice President of Government Affairs Tom Kraus, told 

Although generic drug shortages have been a serious challenge during the pandemic, there are hundreds of drug shortages that occur each year, Kraus pointed out. “In the hope of getting a response from policymakers, COVID-19 shines a light on this, but it is not a new problem.”

Major Initiatives Underway to Solve Problem

Although generic drug shortages have been around for years, new government and industry initiatives may help alleviate future problems.

ASHP is urging the US government to provide “economic incentives” for foreign manufacturers to produce high quality generic drugs and APIs.

“Over half of drug shortages relate to quality problems, which result in a plant coming offline and not producing product. Particularly for low-cost generic drugs, there may not be nearly enough economic incentives for that manufacturer to bring that plant online quality,” Kraus said.

In addition, hospitals and other drug purchasers need some clarity and transparency in relation to when their products will be available. “One way we could connect the dots is let’s publish transparency around the supply chains. Purchasers could steer volume to manufacturers that have a more robust supply chain and could potentially pay a premium for that. That could be a reward for manufacturers,” Kraus said.

In another major effort to prevent generic drug shortages, President Donald Trump recently issued the “Executive Order on Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs Are Made in the United States”, which says the federal government should buy “essential” drugs and supplies made in the US rather than from overseas companies.

“We wouldn’t buy all our essential equipment for a military operation from China or from Russia, so why should we rely so heavily on international rivals for our essential prescription drug supply of generic medications which make up 90 percent of all prescriptions in the US?” NCPA CEO B. Douglas Hoey said in a news release supporting the Order.

“We have seen so many active pharmaceutical ingredients moved offshore, particularly to China and India. When there is a hitch in the supply chain, it ripples through the distribution channels and causes shortages for pharmacies and the patients,” Hoey told 

, there have been problems with generic manufacturing overseas,” Scott Knoer, executive vice president and CEO of APhA told 

®. “I don’t know the right answer to fix it…the pharmaceutical manufacturers can make it cheaper over there. There are potential advantages to making more [drugs and APIs] in the US; however, there will be offsetting increased costs.”

However, although ASHP believes that there is a need for more medications and APIs to produced domestically—and using government purchasing power to incentive manufacturers to produce more domestically is one avenue—that should not come at the expensive of disrupting private sector supply chains and it should not preclude purchasers from utilizing foreign manufacturers, Kraus said.

“We are highly dependent on foreign manufacturers. While we should diversify manufacturing, we shouldn’t do that at the expense of foreign APIs, because they are an important source,” Kraus said. The pharmaceutical supply chain should be more diversified, he pointed out, in order for APIs to originate from a “broad range of foreign countries, so we are actually less dependent on one country.”

The Association for Accessible Medicines (AAM) supports the diversification of the pharmaceutical supply chain, but noted n a news release

that generic manufacturers already make “tens of billions of doses of safe, effective and affordable medicines here in America each year.”

“The pharmaceutical supply chain has demonstrated its resilience during the pandemic by responding to unprecedented demand with strategies that ensured uninterrupted access to essential medicines for millions of patients,” said Jeff Francer, interim CEO of AAM.

However, without addressing the undervaluation of generic and biosimilar medicines in the US with sustainable market supply plans, “we simply cannot secure the domestic market and supply chain with scale and sustainability,” Francer said. To that end, AAM drafted recommendations, 

A Blueprint for Enhancing the Security of the U.S. Pharmaceutical Supply Chain

, which it is discussing with the Trump administration and Capitol Hill.

The resulting rulemaking from the Order must also include a broader solution that does not just mandate increased US manufacturing of medications and APIs, Hoey pointed out. “The payment model has really driven manufacturers offshore because there is so much pressure to get cheap [medications] over quality and over accessibility. If the Administration is going to make a change, it needs to be a holistic change,” Hoey said.

The entire distribution model, including the payment model, must be more transparent because “if the squeeze is going to make pennies per bottle, then there is going to be pressure to repeat the same mistakes that have been made that have resulted in so much of our APIs being offshore,” Hoey said. “This helps, but in a vacuum it is not going to address the issue of shortages and a reliance on a foreign source for critical drugs.”

Executive Order on Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs Are Made in the United States. White House; August 6, 2020. Accessed August 21, 2020. 

https://www.whitehouse.gov/presidential-actions/executive-order-ensuring-essential-medicines-medical-countermeasures-critical-inputs-made-united-states/

NCPA statement on ‘Buy American’ Executive Order. News release. NCPA; August 6, 2020; Accessed August 21, 2020. 

https://ncpa.org/newsroom/news-releases/2020/08/06/ncpa-statement-buy-american-executive-order

Generic and biosimilar industry statement on Essential Medicines Executive Order. New release. Association for Accessible Medicine; August 6, 2020. Accessed August 21, 2020. 

https://accessiblemeds.org/resources/press-releases/statement-on-essential-medicines-executive-order

A Blueprint for Enhancing the Security of the U.S. Supply Chain. Associaton for Accessible Medicine; April 2020. Accessed August 21, 2020. 

https://accessiblemeds.org/sites/default/files/2020-04/AAM-Blueprint-US-Pharma-Supply-Chain.pdf

Articles

Pharmacy organizations stress that government initiatives must include an overall plan for drug pricing, payment model, and supply chain transparency.

Generic Drug Shortage Solutions on the Horizon

The National Association of Boards of Pharmacy (NABP) has issued nearly 50,000 “passports”, or temporary licenses, for pharmacists and pharmacy technicians.

“Launched in response to the [coronavirus disease 2019 (COVID-19)] crisis, this new service supports member state boards of pharmacy in processing requests for temporary and emergency licensure to pharmacists and pharmacy technicians,” NABP said in an email sent to 

NABP Passport allows those seeking temporary or emergency nonresident licensure to submit state-specific requests for an NABP Passport through their NABP e-Profile. NABP then conducts the necessary license verification and disciplinary history review at no cost to the individual or the boards of pharmacy. 

Pharmacy Job Demand Could Grow Because of COVID-19

To streamline the process for applicants, multiple states can be included in each request. As a result, the number of passports issued is higher than the number of requests-which reached 6800 by the end of May.

“Pharmacists must have at least 1 existing license to apply for the Passport, and pharmacy technicians must have a license/registration or hold a certification from the Pharmacy Technician Certification Board or Exam for the Certification of Pharmacy Technicians. Interns and pharmacy businesses can also apply for a Passport if allowed by the state in which they are seeking temporary or emergency licensure,” NABP said.

Currently, 19 jurisdictions have indicated they will make use of the passport program, and 8 states have approved the service for interns. 

Pharmacy licensure testing sites, which were closed at the height of the COVID-19 pandemic, are now reopened, Lemrey “Al” Carter, PharmD, executive director and secretary of NABP, told 

“Most test centers are open and are increasing the capacity in accordance with state and federal regulations,” Carter said. In addition, in late May, 

 gave access to 61 additional select sites to take the NAPLEX and MPJE, Carter said.

The National Association of Boards of Pharmacy (NABP) has issued nearly 50,000 “passports,” or temporary licenses, for pharmacists and pharmacy technicians.

NABP Issues Nearly 50,000 Temporary Licenses for Pharmacists, Techs

The Trump Administration’s Operation Warp Speed, formed to accelerate the development, manufacturing, and distribution of a coronavirus disease 2019 (COVID-19) vaccine, should rely on the “proven record of pharmacies and pharmacists for the rapid deployment of COVID-19 vaccines when they are available,” NACDS said in a 

“For more than a decade since the 2009 H1N1 pandemic, government planning to distribute and administer federally purchased pandemic vaccine to the American public rapidly, efficiently, and safely has included modeling that heavily draws on the strength of chain pharmacies, pharmacists, and private sector distribution channels,” NACDS President and Chief Executive Officer Steven C. Anderson, FASAE, CAE, IOM, wrote on behalf of NACDS in a 

 to the directors of Operation Warp Speed.

Among other objectives, which include the development of therapeutics and diagnostics for COVID-19, Operation Warp Speed is tasked with facilitating substantial quantities of a safe and effective COVID-19 vaccine by January 2021, according to the US Department of Health & Human Services.

Americans appreciate the opportunity to receive their vaccinations at pharmacies, NACDS noted. “With more than 60,000 community pharmacies nationwide-in which nearly 90% of all Americans live within 5 miles of a pharmacy-pharmacies stand ready to support Operation Warp Speed’s efforts to safely and efficiently bring the COVID-19 vaccine to the American public,” Anderson wrote.

NACDS COVID-19 Report: Top Reopening Priorities and How Pharmacies Can Help

In fact, around 1 in 3 adults, or 38 million, who received the influenza vaccine during the 2018-2019 season did so at their community pharmacy, according to the letter.

The organization’s letter detailed federal government studies showing that pharmacists can help vaccinate 25 million more Americans per week, and can help vaccinate 80% of the country seven weeks sooner than if neighborhood pharmacies were not engaged.

 that community pharmacies can mitigate up to 23.7 million pandemic symptomatic cases, yielding a cost savings of approximately $100 billion.

“Many community pharmacies can also deploy mobile vaccine programs that can be tailored to those in underserved, rural, or vulnerable communities,” NACDS said.

1. NACDS Urges Operation Warp Speed to Prepare Now to Accelerate COVID-19 Vaccinations through Pharmacies. News Release. NACDS; June 2, 2020. Accessed June 2, 2020. https://www.nacds.org/news/nacds-urges-operation-warp-speed-to-prepare-now-to-accelerate-covid-19-vaccinations-through-pharmacies/.
	2. Anderson SC. RE: Accelerate Distribution of COVID-19 Vaccines to Americans through Community Pharmacies. NACDS; June 1, 2020. Accessed June 2, 2020. https://www.nacds.org/pdfs/government/2020/NACDS-COVID-19-Vaccine-Operation-Warp-Speed-Letter-6-1-2020.pdf.
	3. Trump Administration Announces Framework and Leadership for ‘Operation Warp Speed’. News Release. HHS; May 15, 2020. Accessed June 2, 2020. https://www.hhs.gov/about/news/2020/05/15/trump-administration-announces-framework-and-leadership-for-operation-warp-speed.html
	4. Bartsch SM, Taitel MS, DePasse JV, et al. Epidemiologic and economic impact of pharmacies as vaccination locations during an influenza epidemic. Vaccine. November 2018. doi: 10.1016/j.vaccine.2018.09.040

Pharmacies and pharmacists can help the rapid deployment of COVID-19 vaccines when available, NACDS said. 

NACDS Urges Trump Administration to Rely on Pharmacists for COVID-19 Vaccinations

This article has been updated with additional information. 

 of the carcinogenic ingredient N-nitrosodimethylamine (NDMA) in certain extended release (ER) metformin products, the first 2 major recalls are underway. Both Apotex Corp and Amneal Pharmaceuticals have issued a voluntary recall of its metformin hydrochloride extended-release tablets, according to the FDA. 

Apotex Corp is voluntarily recalling all lots of metformin hydrochloride extended-release tablets, USP 500 mg, within expiry to retail level. 

“Apotex was notified by the US Food and Drug Administration (US FDA) that one lot of Metformin Hydrochloride Extended-Release Tablets, USP was tested and showed results for N-Nitrosodimethylamine (NDMA) levels in excess of the Acceptable Daily Intake Limit (ADI) and recommended recall of the one tested lot,” Apotex said in a company announcement. 

Out of an abundance of caution, the company is extending the recall to all lots of metformin hydrochloride extended-release tablets in the United States, Apotex added. 

However, Apotex stopped selling this product in the United States in February 2019, and there remains only limited product on the market. To date, Apotex has not received any reports of adverse events related to use of that product, it said.

Amneal is voluntarily recalling all lots of metformin hydrochloride extended-release tablets, USP, 500 mg and 750 mg, within expiry to the retail levels. The affected products were distributed nationwide in the United States directly to wholesalers, distributors, retailers, and repackagers. Amneal is notifying its direct customers via mail by mailing a recall notification letter and is arranging for the return of all the recalled product. Anyone with an existing inventory of the product should quarantine the recalled lots immediately. 

 the carcinogenic ingredient NDMA in metformin products, the agency’s testing found elevated levels of NDMA in extended release (ER) metformin but not in the immediate release (IR) formulation, FDA said in a statement issued to 

FDA has contacted a total of 5 manufacturers with ER metformin above the acceptable level and “will continue to take quick and appropriate action when needed to protect American consumers,” the agency said.

The FDA said that patients should not stop taking their prescription medications without first talking to their health care providers. 

In early February, the agency posted the results of its laboratory analysis showing NDMA levels in some samples of the metformin products it tested. Overall, the levels of NDMA found in metformin ranged from “not detectable to low levels” at the time. 

According to the agency, no sample of metformin that was tested by the FDA exceeded the acceptable daily intake of NDMA.

In December, regulatory agencies outside of the United States recalled some metformin drugs due to low levels of the impurity, prompting FDA officials to test samples of metformin sold within the United States 

1. Apotex Corp. Issues Voluntary Nationwide Recall of Metformin Hydrochloride Extended-release Tablets 500 mg Due to the Detection of N-nitrosodimethylamine (NDMA). Company Announcement. Apotex Corp; May 27, 2020. Accessed May 29, 2020. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/apotex-corp-issues-voluntary-nationwide-recall-metformin-hydrochloride-extended-release-tablets

2. Amneal Pharmaceuticals LLC Issues Voluntary Nationwide Recall of Metformin Hydrochloride Extended Release Tablets, USP, 500 mg and 750 mg, Due to Detection of N-Nitrosodimethylamine (NDMA) Impurity. Company Announcement. Amneal; May 29, 2020. Accessed June 2, 2020. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/amneal-pharmaceuticals-llc-issues-voluntary-nationwide-recall-metformin-hydrochloride-extended

Apotex Corp is voluntarily recalling all lots of metformin hydrochloride extended-release tablets, USP 500 mg, within expiry to retail level.

Author | Christine Blank

Articles

Generic Drug Shortage Solutions on the Horizon

NABP Issues Nearly 50,000 Temporary Licenses for Pharmacists, Techs

NACDS Urges Trump Administration to Rely on Pharmacists for COVID-19 Vaccinations

First Big Metformin Product Recalled, More on the Way