Steris Corporation – Warning Letter – February 9, 2011

“Chemical Indicators (Verify SixCess Class 6 Challenge Packs and Chemical Indicators) Should Not Replace Biological Indicators (BIs)”

Comment

Steris Corporation has developed chemical indicators that have been approved by the FDA to “monitor physical conditions”.  While the FDA has approved this use, they recently issued this Warning Letter because the Steris literature appears to imply that their indicators remove the need for Biological Indicators.  Biological indicators, as noted above by the FDA, measure the sterility assurance of the removal of microorganisms.

“The… FDA has reviewed several brochures and other promotional materials as well as the website for STERIS Corporation’s Verify SixCess Class 6 Challenge Packs and Chemical Indicators.  Chemical indicators are devices within the meaning of section 201(h) of the Federal Food, Drug and Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) Cosmetic Act. The labeling originally submitted by Steris to the Office of Device Evaluation (ODE) in the 510(k)s for the Verify Chemical Indicators and Challenge Packs included the following claim:

“The performance of the Verify (specific name) indicator exceeds that of biological indicator kill and meets the requirements of ANSI/AAMI/ISO 11140 for Class 6 steam indicators.”

SANOFI AVENTIS DEUTSCHLAND GmbH – WARNING LETTER – Part 1

WARNING LETTER  FEBRUARY 9, 2011

SANOFI AVENTIS DEUTSCHLAND GmbH

1. Your firm has not established or followed appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile [21 C.F.R. § 211.113(b)].

Comment

21 C.F.R. § 211.113(b) states that “appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and  followed”.   This includes all aseptic and sterilization processes.

SANOFI AVENTIS DEUTSCHLAND GmbH -WARNING LETTER – Part 2

WARNING LETTER  FEBRUARY 9, 2011

SANOFI AVENTIS DEUTSCHLAND GmbH (Part 2)

2. Your firm has not established separate or defined areas or such other control systems as necessary to prevent contamination or mix-ups during aseptic processing. [21 C.F.R. § 211.42(c)]. For example, 

a) The airflow velocity inside critical areas of the aseptic processing operations of Line (b)(4) was found unacceptable by FDA. The documentary evidence of in-situ air pattern analysis (e.g., smoke studies) reviewed during the inspection confirmed this condition.

TRIAD GROUP – VOLUNTARY PRODUCT RECALL AND FDA 483

TRIAD GROUP – VOLUNTARY PRODUCT RECALL

JANUARY 5, 2011

FOR IMMEDIATE RELEASE – January 5, 2011 – Hartland, Wisconsin, Triad Group, a manufacturer of over-the-counter products has initiated a voluntary product recall involving ALL LOTS of ALCOHOL PREP PADS, ALCOHOL SWABS, and ALCOHOL SWABSTICKS manufactured by Triad Group but which are private labeled for many accounts to the consumer level. This recall involves those products marked as STERILE as well as non-sterile products. This recall has been initiated due to concerns from a customer about potential contamination of the products with an objectionable organism, namely Bacillus cereus. We are, out of an abundance of caution, recalling these lots to ensure that we are not the source of these contamination issues.

Use of contaminated Alcohol Prep Pads, Alcohol Swabs or Alcohol Swabsticks could lead to life-threatening infections, especially in at risk populations, including immune suppressed and surgical patients. To date we have received one report of a non-life-threatening skin infection.

Comment

Prep Pads, Swabs and Swabsticks containing alcohol, typically sold as 70%, act as surface sanitizers/disinfectants.  Alcohol can readily kill vegetative non-spore forming cells, but spore forming microorganisms (spore forming bacteria and mold) are highly resistant.  Alcohol may be filter sterilized to remove bacteria, yeast and mold prior to saturation of the various transfer devices; however, to assure a low bioburden content of the Prep Pads, Swabs and Swabsticks, these carriers should be irradiated to assure the removal of various spore forming microorganisms.  Without the performance of both preventative measures, there is a high probability of spore forming microorganisms being present within either the alcohol, the alcohol carrier or both.

FDA 483 TRIAD GROUP OBSERVATIONS (H & P Industries)

FDA 483 TRIAD GROUP OBSERVATIONS (H & P Industries) 11/29/10 -01/07/11

Comment

Enclosed are three of the forty six Observations along with commentary from the 30 page Triad Group FDA 483.  These three Observations focus upon the training and education within the Triad Group as noted by the FDA during their investigation.  It should be observed within these Observations that the FDA has noted that individuals performing various tasks should possess the various skill sets necessary to perform their functions.  The FDA questions the ability of a chemist who has limited microbiological skills to provide training to personnel.

TRIAD GROUP HARTLAND, WI FORM FDA-483 INSPECTION DATES 11/29/2010 – 1/7/11

Triad Group Hartland, WI  Form FDA-483  Inspection Dates 11/29/2010 – 1/7/2011 

Comment

Enclosed are comments from a total of seven observations representing various Systems to include Laboratory Control, Production, and Material obtained as a subset from the forty six observations within Triad Group’s recent FDA 483 which resulted in a recall of their alcohol prep pads, swabs, and swabsticks.  

Laboratory Control System 

OBSERVATION 19

Each batch of drug product purporting to be sterile is not laboratory tested to determine conformance to such requirements.

Specifically, there is no finished product sterility testing or laboratory (b)(4) testing for sterile alcohol prep pads or sterile alcohol swabsticks.

Comment 

§211.167(a) states “for each batch of drug product purporting to be sterile and or pyrogen-free, there shall be appropriate laboratory testing to determine conformance to such requirements.”  SOPs should exist at each site to manage the sterility testing, USP<71> Sterility Tests, of product sold as “sterile”.  In addition, SOPs should exist that cover such areas as Growth Promotion, (see USP<61> Enumeration of Microorganisms) , as well as the management of all of the equipment to include ISO 5 Sterility Test Hoods, refrigerators and incubators. 

BACTERIA MOST OFTEN SUBMITTED FOR IDENTIFICATION TESTING DURING 2010

FREQUENTLY ENCOUNTERED BACTERIAL ENVIRONMENTAL ISOLATES
Microbiological consulting professionals  are often requested to assist Clients with the identification of various environmental microorganisms to include bacteria that are isolated from their various HVAC and Utility Systems during facility commissioning and on-going operations.  These requests relate to controlling these isolates within Alert and Action Levels and never permitting them to migrate  to Out of Trend (OOT) or Out of Specification (OOS) situations.
During environmental monitoring of ISO 5-8 controlled and classified areas, microorganisms are often isolated from airborne viable, settling, and contact plates and personnel.  Knowing the identification and sources of these bacteria becomes essential to maintaining the control of the environment and minimizing contamination of the non-sterile or sterile process and the aseptic filling of the product.  Personnel require this information to determine what sanitizer, disinfectant or sterilant to use.
Accugenix, Inc., Newark, DE has kindly provided the enclosed list of the fifteen most frequently obtained bacterial isolates during 2010.  These bacteria represent primarily skin microflora and environmental isolates.  One of the microorganisms isolated is also an anaerobe.  Please note that no yeast, molds or streptomyces are included within this list which is presented in Table 1 below along with their frequency.

Highlights from GBPR, Inc.’s May 2011 Events

Risk Based Approach to Cleaning Validation & FDA Compliant Aseptic Processing & Environmental Monitoring Event – New Brunswick New Jersey USA

Novatek International was proud to have sponsored yet another successful Global Biopharmaceutical Resources, Inc. (GBPR, Inc.) event last week in New Brunswick NJ. Such a successful event was due in part to an impressive attendance of high expertise attendees and a variety of knowledgeable presenters. Interactive discussions were openly shared throughout the three day event addressing a variety of appropriate topics that are in line with today’s current industry trends in improving an organization’s overall quality standard and cGMP compliance.

610.12 CBER PROPOSED STERILITY TESTS

PART 610.12 — CBER GENERAL BIOLOGICAL PRODUCTS STANDARDS PROPOSED
 

Enclosed is the summary of the proposed requirements for the revised CBER 610.12 Sterility Test. For additional information, please see below for a summary or visit the enclosed web site for the full release http://www.gpo.gov/fdsys/pkg/FR-2011-06-21/pdf/2011-15346.pdf

The authority citation for 21 CFR part 610 continues to read as follows:

Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 264.

Section 610.12 is revised to read as follows:

§ 610.12 Sterility.

(a) The test.

Except as provided in paragraph (h) of this section, manufacturers of biological products must perform sterility testing of each lot of each biological product’s final container material or other material, as appropriate and as approved in the biologics license application or supplement for that product.

(b) Test requirements.

(1) The sterility test must be appropriate to the material being tested such that the material does not interfere with or otherwise hinder the test.

(2) The sterility test must be validated to demonstrate that the test is capable of reliably and consistently detecting the presence of viable contaminating microorganisms.

(3) The sterility test and test components must be verified to demonstrate that the test method can consistently detect the presence of viable contaminating microorganisms.