Three foreign OTC firms slapped with warning letters for GMP testing violations

Slipshod testing of two over-the-counter (OTC) analgesics along with improper marketing of one led the US Food and Drug Administration (FDA) to issue three warning letters to manufacturers located outside the US. Additionally, the agency continued its crackdown on imported hand sanitizers.
 
The recipients of the warning letters, which were all issued in mid-September, include Laboratorio Pharma International in Tegucigalpa, Honduras, a manufacturer of antibiotics and OTC analgesics; Furley Bioextracts in Semenyih, Malaysia, also an OTC analgesic maker; and Nanomateriales Químicos Avanzados, S.A. de C.V in Apodaca Mexico, a maker of hand sanitizers.
 
The two makers of OTC analgesics were criticized for failing to test incoming ingredients and outgoing products, and for taking a lax approach to stability testing. The hand sanitizer manufacturer was cited for making a hand sanitizer that contained dangerous levels of 1-propanol and not the ethanol indicated in the labeling.
 
All three were given 15 days to respond to the warning letters and have been placed on an import alert.
 
Topical analgesic
 
FDA’s 15 September warning letter to Laboratorio Pharma International SRL recited a litany of good manufacturing practice (GMP) violations tied to the manufacturing of GELAZUL, a topical analgesic.
 
The firm “failed to establish a specification for your active ingredient, menthol, in the finished drug product,” said FDA. “In addition, it does not appear that you tested the incoming component of menthol.”
 
The firm also failed to establish a stability testing program to determine the appropriate storage conditions and expiration dates.
 
Also targeted was the firm’s failure to separate its production facility used to make beta-lactams from its non-beta lactam facility, an important consideration because of “the extremely low threshold dose at which an allergic response could occur,” emphasized FDA.
 
“In response to multiple requests that you clarify beta-lactam production controls, the records provided in each of your responses do not assure complete and comprehensive separation was established between beta-lactam and non-beta-lactam production,” wrote the agency.
 
The firm lacked environmental monitoring data establishing such containment and failed to establish limits on personnel flow in shared areas such as breakrooms and gymnasium facilities.
 
OTC Maker Furley Bioextracts did not test ingredients 
 
Similar GMP problems were also observed in FDA’s 13 September warning letter to Furley Bioextracts for its OTC drug product, PainFix Relief Gel.
 
The firm, in responding to FDA’s request for records under section 704(a)(4), said that finished drug product testing was not conducted on all drug products shipped to the United States.
 
The firm submitted a certificate of analysis (COA) indicating that testing was not conducted to assess the identify of its active ingredient, menthol. “You specifically confirmed in subsequent correspondence that you did not perform any identification and assay testing for menthol in the finished drug product that was shipped to the United States,” said FDA. “Without adequate testing, you do not have scientific evidence that your drug product batches conform to appropriate specifications before release.”
 
In addition, the firm also failed to test incoming components of the active pharmaceutical ingredient used to manufacture the product to determine its identity.
 
The firm also failed to provide adequate stability data to demonstrate that the chemical properties of the drug product are “acceptable” throughout the 3-year expiration date.
 
Additionally, FDA found fault with the product labeling and promotional materials for PainFix Relief Gel. The label’s description of the gel’s ingredients includes such claims as “reduces cartilage degeneration” for turmeric, “scientifically proven anti-osteoporotic” for basket fern, and “powerful anti-inflammatory” for Mandarin orange peel, among other claims. These descriptions, wrote the agency, “demonstrate that these are each an ‘active ingredient’” because each of the ingredients “is intended to furnish pharmacological activity.”
 
The firm’s website also claims the product fights inflammation, treats wounds and ulcers, and improves bone healing, along with other claims that exceed the mere external analgesic property claims permitted by FDA’s external analgesic Tentative Final Monograph. Menthol is the only active ingredient in PainFix Relief Gel that is permitted under the monograph.
Hand sanitizers contained dangerous chemicals
 
FDA is also continuing its crack down on adulterated hand sanitizers, as shown in its 15 September warning letter to Nanomateriales Químicos Avazados S.A. The company’s product, ZANILAST + Gel hand sanitizers, was detained and refused admission at the border following testing indicating the product contained 0.0% ethanol and 41% 1-propanol volume/volume, and not the 65% ethanol level claimed on the label.
 
“This hand sanitizer drug product is adulterated under section 501(d)(2) of the FD&C Act in that the active ingredient, ethanol, was substituted wholly or in part with 1-propanol, a dangerous chemical when in contact with human skin or ingested,” said the warning letter.
 
FDA said that exposure to 1-propanol may cause a host of health problems ranging from irritation to the eyes, nose and throat to serious neurologic and gastrointestinal problems.
 
FDA adds that “1-propanol, not to be confused with isopropyl alcohol or 2-propanol, is not a permitted active ingredient in hand sanitizers intended for the United States.”
 
FDA warning letter to Laboratorio Pharma International SRL
 
FDA warning letter to Furley Bioextracts
 
FDA warning letter to Nanomateriales Químicos Avazados