Abstract
Patients with rare diseases are often confronted with the fact that effective medicines are unavailable or simply not being developed. This situation jeopardizes the health of a large population of vulnerable patients with rare diseases. Pharmacy compounded formulations can provide a safe alternative when authorized treatments are unavailable or unsuitable. Practical guidelines on how to develop and implement pharmacy compounded formulations for patients with rare diseases are limited. The aim of this article is to provide guidance for when and how to apply pharmacy compounded formulations for patients with rare diseases. This is illustrated with two challenging examples: the development and implementation of pharmacy compounding of 1) chenodeoxycholic acid (CDCA) capsules for patients with cerebrotendinous xanthomatosis (CTX) and 2) cholic acid (CA) capsules for patients with rare bile acid synthesis defects (BASD). All critical steps of the development of CDCA and CA capsules are explained and summarized in a practical guideline.
Highlights
Patients with rare diseases are often confronted with the fact that effective pharmacotherapeutic treatments are unavailable
In 2017 chenodeoxycholic acid (CDCA) was reintroduced in Europe (EU) as an authorized orphan medicine for the treatment of cerebrotendinous xanthomatosis (CTX) (EMA, 2016; Leadiant, 2017)
In order to ensure accessibility of effective treatment for our own patients, we developed a pharmacy compounded formulation for CDCA capsules for Dutch CTX patients
Summary
Patients with rare diseases are often confronted with the fact that effective pharmacotherapeutic treatments are unavailable. In order to ensure accessibility of effective treatment for our own patients, we developed a pharmacy compounded formulation for CDCA capsules for Dutch CTX patients. Product validation required due to the amount of batches compounded per year (n > 50) Tests: appearance, identity, LOD, content, content uniformity, related substances, microbiological quality, dissolution- and disintegration rate 6 months (15–25°C) Based on API- and excipients properties described in literature. N/A not applicable, DMF Drug Master File, QC Quality Control, GMP Good Manufacturing Practice, EU European union, LOD Loss on Drying, RSD Relative Standard Deviation, RH Relative Humidity, BASD bile acid synthesis defect, ZSD Zellweger spectrum disorders, API Active Pharmaceutical Ingredient, CTX Cerebrotendinous Xanthomatosis, CDCA chenodeoxycholic acid, CA cholic acid, BCS Biopharmaceutics Classification System, 3β-HSD 3β-hydroxy-Δ5-C27-steroid oxidoreductase, Δ4-3-oxoR Δ4-3-oxosteroid-5β-reductase, Ph. Eur. Preliminary shelf life has been set for 6 and 3 months respectively for the pharmacy compounded CDCA and CA capsules
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