Compounding Laboratories & Pharmacies – How Safe Are Your Products?

 

Introduction

Compounding Laboratories and Pharmacies came into sharp public focus in October 2012 when it was discovered that the New England Compounding Center had mixed tainted steroids that were linked to 45 deaths and sickened nearly 700 people across the US. By April 2013 the number of deaths increased to 53. 

In February 2013 Massachusetts officials ordered 11 compounding pharmacies to completely or partially shut down after a series of unannounced state inspections. Pharmacies that have been shut down must submit a plan and take corrective actions before they can begin producing drugs again. The surprise state inspections revealed that only four of 40 pharmacies fully complied with industry safety standards. On February 6, 2013 The Boston Globe reported, Patient safety specialists, who have long advocated for stricter oversight of the industry nationwide, say that they are not surprised that only a fraction of the state’s sterile compounding pharmacies, which make injectable and intravenous medications, were obeying all the rules.” 

What Are Compounding Pharmacies?

Pharmaceutical compounding is the creation of a particular pharmaceutical product that meets the unique needs of a patient. Compounding pharmacists combine or process appropriate ingredients where medically necessary reasons, such as a change of the form of a medication from a solid pill to a liquid either to avoid a non-essential ingredient that a patient is allergic to or to obtain the exact dose needed were deemed best of particular active pharmaceutical ingredients. Compounding often is done by hospital pharmacists, but is also offered by certain retail pharmacies for various forms of medication. It can be routine, rare, intravenous or oral. Anytime a given drug product is made or modified to have characteristics that are specifically contemplated for an individual patient is known as “traditional compounding.”

Drug shortage and cost pressures have sometimes led to reliance by hospitals on large scale compounding pharmacies to meet their regular needs, particularly for sterile-injectable medications. When compounding moves into small to medium scale mass production of a given product rather than patient-specific production it moves closer to manufacturing rather than compounding.

I recall my great uncle describing his earlier days in the early 20^th Century as a pharmacist after graduating from Northwestern University. He owned a pharmacy that sounded very much like a compounding pharmacy. By the time he retired, however, his pharmacies had evolved toward mid to late 20^th Century operations, still compounding certain ingredients for specific patients, but more often dispensing drugs produced by large pharmaceutical corporations. 

A very good description of compounding pharmacies can be found in Wikipedia under the title of Compounding where they discuss types of patients with unique or unusual medication needs. Compounding allows a physician to tailor a prescription to each individual. For example:

•  Patients requiring limited dosage strengths, such as a very small dose for infants
•  Patients requiring a different formulation, such as turning a pill into a liquid or transdermal gel for people who cannot swallow pills due to disability
•  Patients requiring an allergen-free medication, such as one without gluten or colored dyes
•  Patients who absorb or excrete medications abnormally
•  Patients who need drugs that have been discontinued by pharmaceutical manufacturers because of low profitability
•  Patients facing a supply shortage of their normal drug
•  Children who want flavored additives in liquid drops, usually, so the medication tastes like candy or fruit
•  Veterinarian medicine, or change in dose, or change to a more easily administered form (such as a liquid or transdermal gel), or to add a flavor more palatable to the animal.
•  Many types of bioidentical hormone replacement therapy

How Are Compounding Pharmacies Regulated? 

In the United States, compounding pharmacies are licensed and regulated by their respective states like all other pharmacies. National standards have been created by the Pharmacy Compounding Accreditation Board (PCAB). This means that the 50 State Pharmacy Boards are responsible for regulatory oversight. Accreditation, however, is not mandatory and compliance inspections generally occur only every three years. 

An article written by Lena H. Sun, published in the Washington Post on April 21 2013 discussed a Florida-based compounding pharmacy, Balanced Solutions Compounding Pharmacy, a division of Axium Healthcare Pharmacy of Lake Mary, Florida that voluntarily recalled all lots of its sterile unexpired drug products sold nationwide over concerns that the products may contain bacteria. The Food and Drug Administration asked hospitals and other healthcare providers who received sterile products, including all injectables, from Balanced Solutions, to immediately check their medical supplies and quarantine the products following the company’s recall instructions. Patients who were administered any sterile drug products made and distributed by Balance Solutions should contact their healthcare providers.

Is The Present System Of Regulation Effective?

That the present system is flawed is quite clear. I am certain that some Compounding Pharmacies are creating safe products in sanitary settings and that some states do better than others in regulating Compounding Pharmacies. Unfortunately, patients receiving drugs from unsanitary and/or poorly managed pharmacies have died or been sickened by tainted drugs. Clearly, not all states are equal in the quality of their regulatory oversight.  In previous blogs I have criticized the unequal capabilities of 70+ notified bodies overseeing medical device regulation on behalf of 27 EU member states. It is a problem being addressed by the European Commission. I have similar concerns about the unequal capabilities of 50 state pharmacy boards overseeing compounding pharmacies in the US. 

Patient safety and product safety have to be the paramount concern of regulatory oversight. This has to include safe sanitary facilities, well-trained competent personnel, supplier audits and keen oversight of incoming supplies (including supply testing), sanitary and competent drug compounding, production and delivery. There are several clues that can be borrowed from FDA’s Quality System Regulation. Listed below are a few:

• Management responsibility
• Quality internal and supplier audits
• Competent personnel
• Document controls
• Purchasing controls
• Product identification
• Component traceability
• Production and process controls
• Inspection, measuring and test equipment
• Process validation
• Receiving, process and finished product (drug, compound) acceptance
• Nonconforming product and quarantine
• Corrective and preventive action
• Product labeling
• Product packaging
• Handling
• Storage
• Distribution
• Complaint files 

Improving Regulatory Oversight

The preceding list can be modified to best fit competent regulatory oversight. The present system is broken. FDA is receiving flak for not taking a more aggressive stance in protesting patient safety. Yet, there are historical and legal reasons for the present rather odd system that I will not address at this moment. Clearly, however, we have an erratic system that is causing patient deaths and illness that should not exist in a 21^st Century advanced political system. I don’t expect that the preceding list should be put into a quality system regulation format, but the elements should exist in some intelligent format, be audited and help protect patient health and safety in the United States. 

My primary focus is on International Regulatory Compliance, which includes both the requirements of regulatory authorities and the legal implications of compliance, non-compliance, documentation and sloppy attention to detail that could result in a lawsuit in a US Federal Court or state courts. I was appalled at recent events surrounding compounding pharmacies and compounding laboratories in the United States.

I focus on product safety, product liability and the steps necessary to create a safe product and serve as Legal Expert/Expert Witness where safety has been compromised or ignored resulting in damage, injury and/or death. If you have questions regarding ISO 9001, ISO 13485, FDA’s Quality System Regulation or CE Marking lawsuits you can contact me for a free preliminary consultation at my e-mail address jameskolka@gmail.com