The Agency warned the compounding pharmacies last week, accusing Zion of deficiencies in its manufacture of sterile products and alleging that Compounding Shop made drugs using the unapproved active pharmaceutical ingredient (API), domperidone.
Zion’s warning followed inspections in December 2013 and January this year that landed the firm with a Form 483 after investigators detected bacterial contamination in a batch of calcium gluconate produced at the plant in Arizona.
Similarly, the letter to the Compounding Shop was not its first interaction with US regulators. Inspectors who visited the Florida firm in March and September 2013 discovered – in addition to domperidone use - several current good manufacturing practices (cGMP) violations.
Zion recalled all of its sterile products in December and said it intends to bring its facility into compliance and the Compounding Shop withdrew 660 drug vials and halted all sterile drug manufacturing in May.
Neither firm has commented on the latest warning letters.
The Food and Drug Administration (FDA) acknowledged the earlier recalls, but advised both firms that they need to reassess their manufacturing operations if they want to resume production.
The US FDA has been casting a closer eye over manufacturing operations at compounding pharmacies for the past few years following a number of contamination and quality-related problems with drug products.
Compounding pharmacy has a complex history. In the 1990s the FDA could identify drugs for which compounding posed a threat to efficacy or safety. However, in 2001 it was stripped of these powers after they the US Supreme Court ruled them unconstitutional.
Since the ruling – which prompted the dissolution of the FDA's Pharmacy Compounding Advisory Committee – regulatory monitoring of compounders was sketchy at best with the FDA becoming involved in various legal battles with firms it tried to regulate.
The situation changed dramatically in 2012 when an outbreak of fungal meningitis was linked to a compounding pharmacy that resulted – in 2013 – of the FDA being granted powers to inspect both pharmaceis and facilities that register as outsourcing sites.
The Compounding shop and Zion join twenty two other compounding pharmacies that have received warnings since the Drug Quality and Security Act was introduced in 2013.