Learning to Speak Acronymish
A Beginner’s Guide to the Incomprehensible Dialect of the Biopharmaceutical Industry
The biopharmaceutical industry generates acronyms faster than a four-year-old can ask “Why?” People making the transition from academia or other careers to this industry often feel like they have been dropped into the midst of an isolated tribe that speaks a language no one has ever encountered. To the newbies reading this: fear not. Even those of us who are veterans of the industry still occasionally get the deer-in-the-headlights look when a colleague whips out a shiny new term to demonstrate Ancronymish superiority
It is one thing to know what the acronym stands for; it can be another altogether to understand the concept(s) behind the acronym’s meaning. For instance, the Internet tells me that the accounting acronym “ABM” means activity-based management. Now I know what the acronym stands for. I still have no idea what it means.
This article is intended to assist those who are new to our industry on the path to being fluent in the biopharmaceutical dialect of Acronymish, without listening to recordings or translators or resorting to secret decoder rings. I also promise it will be less difficult than learning Klingon. (Don’t ask how I know.) Each paragraph below is devoted to a single acronym that is widely used in regulated industries and provides my take on the topic.
Starting at the top of the acronym heap: QbD – Quality by Design. In 2004 the FDA produced a guidance document entitled Pharmaceutical cGMPs for the 21st Century. In it, FDA defined QbD as:
- Developing your product to meet predefined product quality, safety and efficacy; and
- Designing your manufacturing processes to meet predefined product quality, safety, and efficacy
Seems like a simple concept? We’ll come back to QbD later.
TQPP (Total Quality Product Profile) is the collection of desired quality attributes (a/k/a outputs) of a finished product. These may be functional attributes, such as strength and purity, or aesthetic attributes, such as taste or appearance. The elements of the TQPP are the goals established for the final product when it is in development. For example, a blood substitute that a) requires no cross-typing, b) room temperature storage, c) has greater than 12 months stability, d) has no other immunogenic properties, and e) has such high oxygen-carrying efficiency that small volumes are efficacious.
A CQA (Critical Quality Attribute), is a particular attribute, characteristic, or quality of the product, either in-process or finished, that will affect its identity, safety, purity, potency, or strength – in short, the specific elements of the TQPP. (See how these acronyms start to work together, almost as if they’re a language unto themselves?) A CQA is literally critical to quality/TQPP, or more precisely, has a direct and significant impact on its actual or perceived quality. A CQA must describe something qualifiable or quantifiable about the product, such as bioburden, endotoxin, concentration, etc., and it must affect an element of the TQPP.
In the blood substitute example, some CQAs may be: no RBC-specific antigens (cross-typing); levels of a preservative that will allow RT (room temperature) storage without negatively impacting the patient or product; the attributes that indicate the product is stable (such as strength, absence of degradation products, etc.); the absence of other antigenic substances, such as HCP (host cell proteins); and the concentration of hemoglobin per mL of finished product.
CPPs (Critical Process Parameters) are operational conditions (a/k/a control inputs) within proven, acceptable ranges that are monitored to detect deviations in standardized production operations and/or changes in CQAs. For example, dissolved oxygen (DO2) is an operational condition that could be critical to the control of growth and health of the cells. In the absence of enough oxygen, cells may die, creating excessive amounts of host cell proteins (impurities), which is almost always a CQA. Therefore, the DO2 level is a CPP for the CQA of HCP level. Centrifuge speed could also be a CPP for the CQA of HCP. All CQAs are process dependent and are proven through good DoE (design of experiments).
Here’s an exception to keep in mind: something that can affect an element of the TQPP may not necessarily be an element of the TQPP. Few, if any, TQPPs specifically list the low pH required for viral inactivation, but that low pH is a CPP because, without it, there is no viral inactivation. Yet if it is too low it may degrade the product. In both instances, pH can potentially affect the purity of the product (CQA).
IPCs (In-Process Controls) are measurements or activities performed to assess and/or affect the CPPs and CQAs during production. An example would be measuring the DO2 with an in-line meter during production (an IPC), in order to control the CPP of 15% DO2, in order to (indirectly) maintain the CQA of <10 ng/mg HCP.
To summarize: one establishes the desired TQPP; through DoE and experience the CQAs are identified, followed by the CPPs necessary to maintain the CQAs within limits, followed by the IPCs needed to keep the CPPs within range. All of this together constitutes Quality by Design (QbD), which we introduced a few paragraphs back.
This list is by no means complete. There are literally hundreds of other terms to learn before you are fluent in Acronymish. But these basic terms will help get you started as you learn to decipher the strange language spoken in the hallowed halls of drug development.
Blog article by: Arvilla Trag
The following three blogs written by my colleagues addressing other issues related to accelerating early stage product development.