FOOD AND DRUG ADMINISTRATION

1.  
   1. The firm did not retrieve allografts that are known to be associated with infections (processed prior to the FDA Recall Order – 8/12/02) from the market. At least twelve distributed allografts are associated with reported Clostridium, Candida, or E.Coli infections. No actions had been taken by the firm at the initiation of the current inspection (2/5/03). [Handwritten: corrected not verified 2/14/03 cdb]
   2. The firm reportedly conducted a review (look back) of all allografts processed between 1998-2002. There was no established plan, procedures or corrective action request (CAR) detailing this review.  [Handwritten: Corrected: verified 2/14/03 cdb]
2. The complaint handling system is deficient in that:
   1. The firm did not document and/or follow-up on a complaint received on 1/2/03 from the agency through Medwatch [ Redacted ] for allograft [ Redacted ] . The heart valve is reported to have been infected with Aspergillus 2 years ago and most recently with Staphylococcus. [Handwritten: (9-5-02)] The complaint was not investigated and, the firm did not file an MDR upon notification of the incident.  [Handwritten: corrected not verified 2/14/03 cdb]
   2. Many complaints are incomplete and/or the files are disorganized. For example,
      1. The firm did not have complete follow-up for complaint (#02-5210367). The complaint (reported to Cryolife on 9/10/02) indicated that a femoral vein was implanted 5/24/02 and the patient developed an infection not normally acquired through other exposures. The complaint report “heavy growth of Corynebacterium. Heavy growth mixed anerobes including prevotella species”. No complaint summary and limited follow-up reports were available in the complaint file when requested on 2/5/03. The complaint was still outstanding.  [Handwritten:Corrected : verified 2/14/03 cdb]
      2. As of 2/10/03 the firm has at least 20 incomplete complaint investigations as that have been outstanding for 174- 255 days.  [Handwritten: Under consideration 2/14/02]
      3. Complaints #02-5210373, #02-5210372, #02-5210326 have been assigned however, specifics about these complaints have not been documented. [Handwritten:Corrections promised 2/21/02]
      4. As of 1/31/03, the firm’s complaint files contained 72 “open” complaints. The complaints have been in open status 144 days (4.5 months) or longer. The complaint investigations have not been reviewed and final dispositions have not been determined. [Handwritten: Under consideration 2/14/03]
   3. The firm’s QA unit does not have oversight for complaint handling and does not review the complaints, complaint investigations or complaint corrective actions/follow-up. [Handwritten: Corrected not verified]
3. The firm’s bacteriostasis/fungistasis testing on the anti-microbial cocktail for [ Redacted ] failed to establish consistent hold times across all challenge organisms and anti-microbial solutions. [Handwritten: under consideration]
4. The firm’s bioburden program is deficient in that:
   1. The firm has not completed the validation protocol and methods development [Handwritten correction, strikethrough:Design cdb 2/14/03] to address incoming bioburden as outlined in the corrective action plan.
   2. As of 2/11/03 the firm has not analyzed [Handwritten correction, strikethrough: trended cdb 2/14/03] the cumulated bioburden data from [ Redacted ] which began in June 2002.
5. The firm does not perform an assessment into the root cause when donor [Redacted] showing different organisms.
   For example:
   

   Donor ID	Pre-culture Results	Post-Culture Results
   [Redacted]	Streptococcus pyogenes	Propionbactrium acnes
   [Redacted]	Enterobacter aerogenes	Propionbactrium acnes
   [Redacted]	Negative Staphpylococcus	epidermidis
   [Redacted]	Pseudomonas fluorscens	Pseudomonas aeruginosa

   [Handwritten: Item under consideration 2/14/03 cdb]

6. The firm has not performed the following equipment qualification:
   1. The three [Redacted ] being used on human tissue (EO113F, EO113J, EO113G) did not have complete validation; the Performance Qualifications were not done. [Handwritten: Corrected not verified 2/14/03 cdb]
   2. Current Preventative Maintenance procedures for the [Redacted ] are not in accordance with the manufacturer’s recommendations. [Handwritten: corrected not verified 2/14/03 cdb]
7. On 2/3/03 an area of rust/corrosion was observed along the bottom back panel of Laminar flow hood (E00491) located in the Microbiology Lab. [Handwritten: corrected not verified 2/14/03 cdb]

The observations of objectional conditions and practices listed on the front of this form are reported:

1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or
2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration.

"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."