Sharon Flank, PhD, sflank@infratrac.com, is CEO at InfraTrac.

Sharon Flank

Before industrialization, pills were formulated by compounding, mixing, rolling, cutting, and finishing for a particular patient. This process remains useful when mass production fails to create a version that works for an individual, whether because the dose is incorrect or an unacceptable ingredient such as an allergen must be avoided. Compounding for a single individual is regulated differently from mass production (1) in every jurisdiction; although, it is worth noting that even trituration via mortar and pestle must be performed using gloved hands, in a clean environment, free of vermin, standing water, and the like (2). Three-dimensional printing (3DP) offers many advantages, particularly for personalized medicine, but, from a legal and regulatory perspective, regardless of specific print technique, it is neither exactly compounding, nor is it exactly mass production. The technology can be used to develop novel drug delivery options, potentially manufactured at scale and thus falling under existing FDA manufacturing regulations. It can be employed for distributed manufacturing, introducing issues of portability that FDA is addressing in its Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) discussions (3). Here the focus is more on point-of-care production, either for a single patient or, potentially, for a small group as in a children’s hospital. Wise regulatory choices can allow 3DP to flourish to patients’ advantage, building on its strengths and, crucially, adding options for better patient care. A focus on the intersection of areas of need (dose customization, polypills, allergen avoidance) with relative simplicity will lead to earlier success.

Compositional changes affect bioavailability and cannot be implemented at the point of care, but shape and size variations can be pre-tested, bounded, and made available for the dispensing pharmacist to control. One approach to such bounding is the creation of so-called pharma-inks, pre-formulated but with dosing to be controlled at the point of care; another is the use of cartridges. Neither of these approaches offers allergen avoidance, but it is possible that there will be other intermediate-based offerings that allow limited customization (e.g., from a list of APIs according to a validated formulary). While it is unlikely that 3DP will be as fast as industrial-scale manufacturing such as tableting and capsule-filling, the ease of variation offers advantages whenever changeability is a positive attribute. This paper addresses the interplay of positive variation (e.g., for personalized medicine) and negative variation (i.e., repeatability failure).

The variety of 3DP technologies has been discussed in depth, including for drug printing (4). All share several basic commonalities. First, raw materials can be placed in a particular location in a dose form, with the result that geometric features are available to manipulate drug delivery parameters. In conventional manufacturing, coating offers this option, but only in a limited fashion. Second, the raw materials are utilized first in a flowable form (powder, liquid, gel), and then, depending on the method, one or more techniques are used to solidify the resulting dose. In the case of filament-based printing, this is a two-step process, in which a coil of thin filament is first created, generally via hot-melt extrusion, and then fed through a printer so that the shape can be manipulated.

Submitted: July 1, 2024
Accepted: July 15, 2024

 Title 21, 225.1 (Government Printing Office, Washington, DC). 

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=225.1

Guidance for Industry, on Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug and Cosmetic Act

CDER Framework for Regulatory Advanced Manufacturing Evaluation (FRAME) Initiative, Distributed Manufacturing and Point-of-Care Manufacturing of Drugs, 

Gary Ritchie, InfraTrac gritchie@infratrac.com, is director of Scientific Affairs at InfraTrac. Sharon Flank

, PhD, sflank@infratrac.com, is CEO at InfraTrac.

To whom all correspondence should be addressed.

®
Vol. 48, No. 12
December 2024
Pages: 22–25

When referring to this article, please cite it Ritchie, G.; Flank, S. Legal and Regulatory Perspectives on 3D Printing: Drug Compounding Applications. 

Articles

This paper explores the legal and regulatory framework around 3D drug printing, particularly for personalized medicine, considering regulatory compliance, business concerns, and intellectual property rights.