New Hope for Pharmaceutical Compounding

What has changed since the New England Compounding Center disaster?

(This is the first in a series of articles about the compounding pharmacy industry. )

A long time ago in a galaxy far, far away…OK, so it was like 11 years ago in the northeastern United States…tragedy struck. If you’re already well-acquainted with the history of pharmaceutical compounding regulations, you know how this story begins. However, I encourage you to read on for a nice little refresher. If you’re not familiar with this flashpoint in the industry, please continue reading for an important history lesson on the largest public health crisis ever caused by a contaminated pharmaceutical drug. 

In September 2012, the US Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA), along with local and state health officials, began investigating a multistate outbreak of fungal meningitis among patients who received contaminated steroid injections. The contaminated medication eventually traced back to the now defunct New England Compounding Center (NECC) in Framingham, MA. Tragically, the FDA had previously visited the site and found sterility issues but lacked the authority to impose or enforce any changes to the site. The NECC was permitted to operate as a pharmaceutical compounder due to regulatory gray areas at the time. Despite their facility operations resembling an FDA-regulated drug manufacturer, they were subject only to regulatory oversight by state boards of pharmacy. As a result of NECC producing medications under insanitary conditions, the outbreak of fungal meningitis traced to 20 states, killing 64 people and sickening 753 others.

The pharmaceutical compounding industry plays a crucial role in providing customized medications to patients with unique needs when no FDA-approved drug is available. However, the industry faced a significant turning point in 2012 after the NECC tragedy exposed critical gaps in the regulatory framework surrounding compounding pharmacies. In response to this outbreak, Congress passed the Compounding Quality Act (CQA) as part of the broader Drug Quality and Security Act in 2013. 

This legislation defined two categories of compounders. What we think of when we consider traditional compounding pharmacies were defined as ‘503A’ pharmacies. They are permitted to compound for individual prescriptions only, not bulk production of drugs. A 503A compounding pharmacy must comply with state boards of pharmacy regulations as well as requirements set forth in USP <795> Pharmaceutical Compounding-Nonsterile Preparations, USP <797> Pharmaceutical Compounding-Sterile Preparations, and any standards referenced within those chapters. They are not required to comply with current Good Manufacturing Practice (cGMP) regulations. The other category of business defined by the CQA was the ‘503B’ outsourcing facility. Upon voluntary registration with the FDA, 503B outsourcing facilities fall under the jurisdiction of the FDA and are expected to comply with cGMP requirements in 21 CFR Parts 210 and 211 and FDA guidance documents specific to 503B cGMPs.  Any compounding pharmacy not complying with applicable regulations or failing to register as an outsourcing facility may be subject to the regulations set forth for drug manufacturers in the Food, Drug, and Cosmetic Act.

Fast forward to the present. Compounders are making plans to modernize the way they produce medications by determining their path to compliance with the updated USP <795> and USP <797> chapters that become enforceable in November 2023. After many years of hard work, diligence, and spirited discussion between the USP and the industry, revisions to the chapters provide a clearer roadmap to increase the safety of compounded drugs and should be treated as a minimum regulatory framework for the safe production of drugs.

Despite current regulations, compounders produce drugs under less regulatory pressure compared to companies in the pharmaceutical industry that manufacture FDA-approved drugs. Perhaps paradoxically, compounders are expected to maintain product quality and ensure patient safety to the level that FDA-approved drugs are held to. Due to a different regulatory environment and other drivers within the industry, compounded drug products have a storied history of various quality issues. In November 2020, the FDA released Insanitary Conditions at Compounding Facilities as a guidance for industry, describing patterns of insanitary conditions observed over years of inspecting compounding facilities. This guidance was issued to help facilities and regulators identify, correct, and prevent insanitary conditions that could cause a drug product to become contaminated or cause people harm. Compliance with USP chapters is necessary, but not sufficient, for success. It is also important to learn what not to do by reviewing this guidance as well as warning letters and recalls in the industry.

Let’s face it – becoming compliant with updated USP chapters can be hard, but it doesn’t have to be. In April 2023, my colleague Gary Liu provided an in-depth look at multiple QC challenges facing the compounding industry. There is a need for faster results than traditional sterility methods can provide to avoid unnecessary extra days that can jeopardize patient safety and limit the usable shelf life of the product (I’m looking at you, Category 2 compounded sterile preparations). How would sterility results in less than a week impact your production schedule and marketability of your products? What about minimally hands-on, cartridge-based endotoxin tests that produce results in less than 20 minutes? If you find mold on the surface of your ISO 5 area, do you want to wait one week to ID it or would a same-day turnaround time work for you? (Spoiler alert – faster is better)! Consider what positive financial impacts and operational efficiencies a 6-day rapid sterility test, 20-minute endotoxin test, or a same-day turnaround time for a critical microbial identification would have on your business.

There are more resources than ever before from the USP, the FDA, consultants, and third-party vendors. These microbial solutions for your business provide new hope for the future by helping ensure the safe production of compounded drugs. How are you going to improve your current processes and become compliant with the updated chapters?

Interested in learning more about compounding pharmacy? Check out this article on endotoxin testing and compounding pharmacy products.

Dr. Doug Botkin, PhD, is a Technology and Market Development Manager at Charles River Laboratories. He is a subject matter expert in the Microbial Solutions group, focusing on Accugenix products and services for microbial identifications. Doug has over 24 years of experience in infectious disease research, spaceflight microbiology, and pharmaceutical microbiology, including working as a QC microbiologist at 503B outsourcing, cell and gene therapy, and non-sterile manufacturing sites. He holds a bachelor’s degree in Biological Sciences from Illinois State University and earned his PhD in Microbiology and Molecular Genetics from The University of Texas Health Science Center at Houston.

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