Care-Tech Labs handed 12-item 483; OOS cited.

Care-Tech Labs, St. Louis, MO, Lenexa District

Despite seven voluntary corrections since its second inspection, Care-Tech Labs, St. Louis, MO, still received a 12-item 483, including citations for retests not done on original samples, releasing products for distribution that did not meet specifications and a lack of OOS investigations/reports.

The company, which makes OTC topical creams, lotions and cleansers for skin irritations, wound treatment and antimicrobials, also was cited for inadequate microbiological controls in lab, lack of manufacturing process validation, no change control procedures, lack of cleaning validation and lack of maintenance schedule.

Erika Butler of FDA's Lenexa, KS, office conducted the December 2003 inspection of the firm's quality system, facilities and equipment, materials systems, productions systems and laboratory control systems, according to FDA records.

According to inspection documents, the firm's "acceptance criteria for sampling and testing conducted by the quality control unit is not adequate to assure that batches of drug products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release."

Specifically, the EIR noted, lot 2414 and 2402 of Tech 2000 dental rinse "failed microbiological testing and a retest of different sample was performed, not on the original sample taken for finished product testing. Lots were released and distributed after retests showed negative results for microorganisms."

Butler told John Brereton, president of Care-Tech, that in order to retest an original sample, a complete investigation must be one concerning the OOS. Only when the investigation is documented and completed is a retest on the original sample permitted.

According to the 483, Butler also cited the firm because "drug products failing to meet established specifications are not rejected."

Specifically, "this practice was observed after reviewing the batch records for years 2002 and 2003 for products such as Tech 2000 dental rinse, Techni-Care Surgical Scrub, Care Creme antimicrobial, and Peel-Paks antimicrobial hand brushes," the EIR noted. Specifications failing finished product testing included

* Percent of chloroxylenol chloride, active ingredient in Techni-Care Surgical Scrub (lot 2182)

* pH in lots 2248, 2387, 2388, 2391 and 2394 for Tech 2000 Dental Rinse

* Specific gravity in lots 2295, 2339, 2358, 2362, and 2364--all for Techni-Care Surgical Scrub

* Viscosity in lots 2284 and 2333 for Care Creme

The investigator asked Brereton why lots 2182, 2160 and 2164 were passed even though the active ingredient was not in spec. He replied "it was most likely due to lab error since the chemist was still perfecting the HPLC method." Butler responded that an OOS investigation should have been performed to determine if it was lab error.

Next, Butler cited the firm for "a failure to thoroughly review the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been thoroughly distributed," the EIR stated.

Specifically, the EIR noted:

* No deviation report or out of specification report was done for failing active ingredient in lots 2136, 2160, 2164, and 2182 for Care-Creme wound treatment and Techni-Care Surgical Scrub.

* Inadequate batch failure investigation for lots 2231, 2371, 2374, 2375 of Tech 2000. "No written failure investigation report was generated for the lots," the EIR stated.

* No deviation or out of specification reports were generated for drug products that did not meet specification on stability testing for 2003.

The 483 also noted that Care-Tech Labs did not establish "procedures designed to prevent objectionable microorganisms in drug products not required to be sterile."

Specifically, equipment qualification was not performed, an undisclosed technique used on the growth promoting plates was not validated, and "test methodology for microbiological contamination does not test for objectionable microorganisms, such as gram negative organisms in finished drug products," the 483 stated.

According to the EIR, this was a repeat violation from a January 2000 inspection. The firm "promised correction and plan to work out a time-frame when validation/qualification can be completed."

Further, the firm did not establish control procedures to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.

For example, "there have been no validation studies, either prospective, retrospective or concurrent of manufacturing process used to produce drugs," the EIR stated. Also, "there have been no validation studies of the purification process of the water by the water sterilizer."

Next, Care-Tech Labs was cited because "the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed," inspection documents stated.

Specifically, FDA wrote that "there are no written procedures defining the quality control unit and change control. The firm has no written change control procedures that will provide for full description of the proposed change."

Regarding lack of written procedures for the cleaning and maintenance of equipment, the 483 stated: "Specifically, there have been no cleaning validation studies...for the filling lines, batch tanks or line reservoir to ensure residues and objectionable organisms have been reduced to an acceptable level."

For records not being kept for the maintenance of equipment, the investigator noted "there is no written maintenance schedule on how frequently the gaskets on the filling line need to be replaced. This can be a source of microbiological contamination."

Brereton admitted "the gaskets are not on a maintenance schedule," according to the EIR, adding he only changed them when they started to leak.

In the investigator's final discussion with management, Brereton stated "the validation of the manufacturing processes and qualification of equipment would be a priority."

The EIR also stated that Brereton was considering hiring a consultant to help with validation and provide general guidance on manufacturing issues. Butler "strongly encouraged" Care-Tech Labs to enlist the help of a qualified consultant. Butler reminded Brereton that if GMPs are not adhered to, "then the product is considered adulterated and warning letter, seizure, injunction, or civil penalties may follow," the EIR concluded.

Phone calls seeking an update were not returned before deadline.

Care-Tech Labs, St. Louis, MO, 11/17-12/2/03, Doc. 109621M, $12.00 plus retrieval.