Effective Immediately: FDA Releases Guidance for Compounding Industry in Response to Beta-Lactam Shortage

Beta-Lactam Products Like Amoxicillin Oral Antibiotics are in Short Supply Across the World

The Food and Drug Administration (FDA) added amoxicillin oral powder for suspension to the drug shortage list and has released guidelines on the creation of compounded versions of specific beta-lactam oral suspension products due to the current lack of amoxicillin oral antibiotic powder for suspension.

Amoxicillin is a beta-lactam antibiotic that is commonly used to treat bacterial upper and lower respiratory infections in children. Compounding this drug in an environment without the necessary safety precautions could result in the contamination of other drug products. Some patients may experience allergic responses that are fatal.

The FDA Reports Drug Shortage

Amoxicillin is frequently administered to children to treat conditions like middle ear infections, Streptococcus A and other bacterial infections like strep throat, pneumonia, skin infections, and urinary tract infections among others.

Amoxicillin oral antibiotic powder for suspension products are currently on the FDA’s drug shortage list.

About four out of five pharmacies reported issues filling prescriptions for the antibiotic amoxicillin in a National Community Pharmacists Association survey completed by 332 stores at the end of January. About 93 percent were short in children's pain and fever medicines, according to the survey.

High demand for amoxicillin oral antibiotic suspension products, coupled with requests for clarification on the preparation of compounded versions, have prompted the Federal Agency to issue recommendations for pharmacists in state-licensed pharmacies and federal facilities not registered as outsourcing sites.

The FDA Releases Final Guidance on Beta-Lactam Shortage

The FDA issued a final guidance paper at the request of the Alliance for Pharmacy Compounding (APC), outlining the minimal precautions that pharmacies that compound beta lactam oral antibiotic suspension products must take to reduce the risk of cross-contamination with other products.

The FDA’s final guidance document is available here for download.  Some of the major points are listed below, as taken from the FDA Guidelines document:

1.     Use of FDA-approved beta-lactam tablets and capsules instead of bulk drug substances to compound the beta-lactam oral antibiotic suspension product.

2.     Temporal segregation of the compounding of these oral suspensions from non-betalactam products.

For facilities that intend to compound beta-lactam oral antibiotic suspensions, monitoring and reporting allergic reactions from accidental beta-lactam exposure from the use of non-beta-lactam products is highly recommended.

In November the FDA’s guidance document explained:

“There is currently an acute shortage of amoxicillin oral antibiotic powder for suspension. Amoxicillin oral antibiotic powder for suspension products currently appear on FDA’s drug shortage list. Amoxicillin is widely used for the treatment of bacterial upper and lower respiratory infections in the pediatric population, among other uses. As a result of this shortage, there is an urgent need to increase the supply of these beta-lactam oral suspension products. FDA has received a number of reports related to increased demand for amoxicillin oral antibiotic suspension products in particular. FDA has also received requests for clarification about preparation of compounded versions of those products from FDA-approved tablets and capsules.”

DOWNLOAD THE FINAL GUIDANCE DOCUMENT

The FDA’s final guidance states:

“FDA’s insanitary conditions guidance describes the processing of beta-lactams without complete and comprehensive separation from non-beta-lactam products as an example of an insanitary condition the Agency has observed. However, during the time that beta-lactam antibiotic powder for oral suspension products are on the FDA shortage list … compounders under section 503A of the FD&C Act that prepare beta-lactam oral antibiotic suspension products that appear on FDA’s shortage list without complete and comprehensive separation from non-beta-lactam products should take at least the following minimum steps to mitigate the potential risk of cross-contamination and reduce risk to patients.”

Pharmacy’s Appreciate the FDA’s Quick Turnaround Time on Guidance

The Alliance for Pharmacy Compounding (APC) alerted the FDA about the shortage.

“Both hospital and retail pharmacies knew they had the ability to compound amoxicillin suspension from commercially available tablets or capsules,” Scott Brunner, CEO of the APC, said in a statement.

“But they were unable to meet that requirement of complete and comprehensive separation from other products—and so they were concerned, rightly, about the potential for regulatory action to be taken against them for serving the need of their patients.”

Brunner was pleased with the FDA’s ability to act swiftly on this issue.

“This guidance is a remarkably rapid and helpful response from the agency, and I know compounders will take seriously their commitment to mitigate risks to get these medications to the children who need them,” he said.

As reported by the APC, these are the main steps a compounding pharmacy should take: “The steps include only compounding from FDA-approved beta-lactam tablets and capsules instead of bulk drug substances; use of dedicated or disposable equipment, utensils, and personal protective equipment; trituration of the FDA-approved product after wetting it with a quantity of the suspension vehicle sufficient to eliminate formation of product dust; and six other essential steps.”

Here are the Companies Reporting a Drug Shortage

Currently, as of January 11, 2023, and according to the Food and Drug Administration (FDA), these companies have reported a shortage in “Amoxicillin Oral Powder for Suspension” and has been labeled “Currently in Shortage”:

  • Aurobindo, USA

  • Hikma Pharmaceuticals

  • Sandoz

  • Teva Pharmaceuticals

As of November 2022, here are the reasons for shortages, according to the respective pharmaceutical companies:

  • Aurobindo refuses to provide availability information.

  • Hikma is allocating amoxicillin to current customers to meet the planned contracted demand.

  • Rising has amoxicillin capsules and tablets available.

  • Teva did not provide a reason for the shortage.

The Amoxicillin Oral Powder for Suspension shortage was originally reported by the FDA on October 28, 2022 in the therapeutic categories: Anti-Infective; Pediatric.

You can visit the link here regularly for updates.

FDA’s List of Shortages and Growing Concern About China’s Stronghold Over Prescription Drugs

As of January 2023, 123 drugs were listed on the FDA's current list of drugs that are in shortage. The current list includes a lot of what you’d find in the hospital ICU or emergency room, and include several drugs that are used by paramedics.

Hospitals steadily try to ensure adequate supplies of drugs that are in shortage or to substitute them. In the University of Chicago study, one-third of hospitals had to ration drugs at least once. 

Concerns are raised about reliance on any single country, like China, the world’s largest producer of active pharmaceutical ingredients (APIs). 

In a 2019 report from the U.S.-China Economic Security Review Commission determined that the U.S. is heavily reliant on drugs either sourced from China or include APIs that are sourced from China. This is especially true for generic drugs.

The Shortage Likely Won’t End Anytime Soon

Two major manufacturers say America's amoxicillin supply will continue to be limited for months and that constraints will continue at least through April of this year. The last quarter of 2022 had shortages of 295 medicines, which the most in a quarter since at around 2018.

Pharmacist Resources

FDA Drug Shortages: Search the FDA’s database for generic name or active ingredients to show results if the particular drug is in shortage.

Report adverse events: The FDA asks pharmacists to report quality problems with the use of compounded drugs or adverse events. Report problems to the FDA’s MedWatch Adverse Event Reporting program. Forms can be printed then submitted via fax at 1-800-FDA-0178.

Comments: Pharmacies can also submit electronic comments to https://www.regulations.gov/ online, or submit written comments to: Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

Where Does Your Facility Stand?

If you’re looking to become compliant with the new USP requirements or if you wonder how you measure up, let consultants at Restore Health Consulting LLC perform a USP 797 gap analysis to assess your pharmacy or hospital compliance status against the new minimum standards and lead remediation planning if needed.

Amy Summers