FDA ISSUES — MEDIA GROWTH PROMOTION STUDIES McNEIL-PPC, DELTEX PHARMA, RIBBON PHARMA & CHEMICAL, COLUMBIA PRESBYTERIAN MEDICAL CENTER

FDA ISSUES — MEDIA GROWTH  PROMOTION STUDIES McNEIL-PPC, DELTEX PHARMA, RIBBON PHARMA & CHEMICAL, COLUMBIA PRESBYTERIAN MEDICAL CENTER

Comment

Comments Regarding Proposed Changes to USP General Chapter <823> Radiopharmaceuticals for Positron Emission Tomography-Compounding were recently made to the USP as they move forward in their decision process.  One of the sections dealt with those FDA 483/Warning Letters  where various Companies failed to perform the requisite Growth Promotion testing either required by USP<71> Sterility Tests or USP<61> Microbiological Examination of NonSterile Products: Enumeration of Microorganisms and the FDA has cited these Companies.  These examples have been enclosed below for your review.

For example:

FDA-483 McNeil Consumer Healthcare, Division of McNeil-PPC, Inc 4/19-4/30/2010

OBSERVATION 12

“Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that components and drug products conform to appropriate standards of identity, strength, quality and purity.  Specifically, scientific justification does not identify the reason(s) why the firm does not test TSA, a non-selective general microbial growth medium”(my Bolding).

Warning Letter — Deltex Pharmaceuticals Inc 31-Oct-08;  Consent Decree of Permanent Injunction against Deltex Pharmaceuticals Inc., January 18, 2011

“4. Failure to conduct appropriate laboratory testing, as necessary, of each batch of product required to be free of objectionable microorganisms, as is required by 21 CFR § 211.165(b). For example, your firm does not conduct any preparatory testing on drug products to assess their possible inhibitory effects on microbial growth prior to testing for the presence of microorganisms. In addition, there is no growth promotion testing on the batches of media used. We acknowledge the pledge in your September 2, 2008, response to conduct preparatory testing on most product formulations by October 31, 2008. However this response is unsatisfactory because it includes no commitment to conduct growth promotion testing on each batch of growth media used. Because of the possible impact of exposure to adverse conditions while in shipment, reliance on a suppliers’ Certificate of Analysis (COA) alone is not sufficient to provide a necessary degree of assurance that the purchased media will perform adequately. The performance of each lot of growth media used should, at a minimum, be confirmed upon receipt or before the first use”.

Warning Letter – Ribbon Pharmaceutical and Chemical Products, May 27, 2010

1. Your firm has not established appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile [21 C.F.R. §211.113(b)]. …In addition, the test material and the validation procedures used by your firm compromise the recovery of microbial contaminates.  For example:

a. Placebo mediums should be evaluated for their ability to support growth.  Your response states that the placebo used in the process simulation is sodium phosphate in different forms(solution and anhydrous) and sodium chloride solutions (1%).  The principle of using simulation media is to create conditions representing the greatest possibility of recovering existing contaminants.  Your response does not provide scientific evidence and documentation that the placebo medium (solution and anhydrous) used during process simulation adequately supports growth promotion of viable organisms.  In your response to this letter, provide the rationale and the supporting study summary report for using each of the placebo growth media (including the medium in its anhydrous state) in your process simulations.

Warning Letter Columbia Presbyterian Medical Center, December 22, 2008

5. You failed to establish appropriate sterility test procedures and to conduct testing appropriately. For example,

a. The (b)(4) used for detection of anaerobic organisms was not suitable for use. Observation of multiple lots of FDG Injection (e.g. F053008-01, F05290801, F052808-01) in FTM tubes undergoing sterility testing showed that the media failed the color indicator requirement, indicative of an excess amount of oxygen. Consequently, the sterility test has been ineffective in detecting spore-forming anaerobic microorganisms (my Bolding).