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March 13, 2018

Building a Research Pharmacy to Support Early Phase Clinical Investigators
By Robert B. MacArthur, PharmD, MS


Renovation of the Hospital Pharmacy has started!

The renovated pharmacy will have a greatly expanded range of products that can be compounded for Hospital and University investigators.

One key component is the state-of-the-art cleanroom.

The cleanroom has been designed to comply with United States Pharmacopeia (USP) chapters <797 > and <800>, and New York State regulations, among others. These USP chapters apply to sterile non-hazardous and sterile hazardous products, respectively. Importantly, the current rapidly evolving FDA regulations that apply to sterile compounding all require compliance with these USP chapters, and therefore such compliance is being built into the facility. These USP chapters are extremely broad in scope, and provide guidelines that apply to batch records, labeling, environmental quality, product quality control, quality assurance, product testing, storage, beyond-use-dating, staff training, and product transport.

The cleanroom itself is composed of 3 rooms, an anteroom (staging, handwashing, gown, glove), a buffer room (compounding, production), and an inventory room. All three rooms are negatively pressured to the surrounding environment, to prevent air and particulates from escaping to the outside environment. There are controls in place that prevent the anteroom door from being open at the same time as the buffer room door. This prevents inward air flow, stopping outside air from entering the ante and buffer rooms. Below, figure 1 depicts how air flows in the buffer room. From the ceiling, sterile HEPA filtered air blows straight downward and exits via floor level exhaust vents. This air is then filtered and exhausted outside, and no air is recirculated back into any of the rooms. The buffer room “air curtain” protects both the product from particulates (viable and non-viable) and operators from the product. This minimizes operator exposure to vapors and particulates that are released when working with active ingredients and formulated products. The sterile compounding procedures are performed within a laminar flow hood, within the buffer room. The area where products are compounded is referred to as the “Containment Primary Engineering Control” (CPEC) where air quality is ISO Class 5, or better. Effectively there are 2 solid walls and 3 unique air environments between the outside and the CPEC. Interestingly, within the buffer room, sterile air is changed at least 30 times per hour, while across the CPEC surface, sterile air flows are approximately 100 feet per minute.

Having access to this cleanroom brings a number of advantages and service improvements.

Sterile products can be assigned Beyond-Use-Dates (BUD, similar to an expiration date) as outlined in USP<797>. This allows the pharmacists and investigators to decide which BUD is best for a given study product, and then they can tailor the compounding procedures, packaging, and storage methods per USP BUD requirements.

The air handing described (USP<800> compliant) allows for working with small batches of chemotherapy, hormones, immunomodulators, vaccines, peptides, proteins and other compounds. Such ingredients, and the resulting compounded finished products, will all be stored in the negatively pressured inventory room, which has 12 air changes per hour. Of note, phase 1 sterile investigational products may be compounded in such a cleanroom when complying with Good Manufacturing Practices (see Guidance for Industry CGMP for Phase 1 Investigational Drugs, CDER, CBER, ORA, July 2008).

On a historical note, during the renovation, we uncovered stored medication packages from an earlier era in medicine. Three of these products are shown in figures 2, 3, and 4, along with a description of how they were used at the time.

We are very excited about the possibilities that the renovation and cleanroom bring to the pharmacy and the Rockefeller research community, and look forward to providing expanded services to Hospital and University Investigators