CURRENT GOOD MANUFACTURING PRACTICES

Case #1: IV Bottle Contamination (Abbott Laboratories)

GROUP 4

GROUP MEMBERS

• SHAHMILA A/P SHANMUGAM (AN120225)
• TENG HUI CHEN (AN130282)
• YASHNI A/P GOPALAKRISHNAN (AN130179)
• KANCHANA A/P VIJAYAKUMARAN (AN130228)
• NOR FATIN NABIHAH BINTI ABDULLAH (AN130013)

OVERVIEW

1.Cases Background
2.Company Background
3. Abbott Lab IV Bottle New Cap Design (1970)
4. Contamination Illustration
5. Outcome
6. Investigation Findings
7. Recommendations
8. Applicable cGMPs
9. Conclusion

Cases Background

IV Bottle Contamination

• October 1970 – March 1971
• Containers with screw-cap closures contaminated with bacteria
• 150 bacteremias caused by Enterobacter Cloacae
• Involved about 8 US hospitals

IV Bottle Contamination

• Commonality observed = all used fluids & IV system manufactured by Abbott Lab
• Septicimia (blood poisoning) cases

Enterobacter Cloacae?

~Gram –ve bacteria
~Relatively common “ICU bug”

~Opportunistic pathogen among the vulnerable (infants & elderly)

Company

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Abbott Laboratories (1970)

• A diversified company ~Pharmaceutical & Healthcare Product Company
• ~ consumer goods (Selsun, Murine, Similac) 1960’s ~ hospital products (monitors, IV equipment, drug testing)

Abbott Laboratories (1970)

• Cyclamate ~ (an artificially prepared salt of Na/ Ca used as sweetener)
• Largest supplier of IV fluid in US

Abbott Lab IV Bottle

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• When the cap has been removed and replaced that migration of bacterial organism from the cap lining may occur.
• Intrinsic contamination of the company's screw-cap closure for infusion bottles which was sealed with a newly introduced elastomer liner.

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• There are any pathogenic organisms under the cap, the microorganisms would get into the solution
• Cooling closures actively drew moisture through the thread interstices into the inner-most depths of the closure.

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• The red-rubber liner used in the company's screw-cap closures before the introduction of elastomer contained a broad-spectrum antimicrobial inhibitor.

Illustration..

Previously they had a lining under the screw-type cap that had paper with several layers, maybe six or seven layers of paper, that was in the screw cap.

Then they decided to change the inner lining to a plastic type. It was learned that the smooth plastic liner in the cap of the IV large volume bottle did not fit tight under the cap.

The plastic liner in the cap did not fit into ridges that might be on top of the glass. So when in the processing of large volume parenterals they were heated to sterilization temperature, and the bottles were then cooled in water causing a vacuum
which sucks in the cooling water.



This water was drawn into the bottle. The water got under the cap. That's what was causing the septicemia in patients.

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OUTCOME

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• Contaminated bottles linked to > 434 infections 49 deaths
• Abbott forced to recall 3.5 million bottles of IV Fluid

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• IV Sales decrease 84%
• Abbott redesigns IV Bottle Seals
• Litigation Ensues

Investigation Findings

Abbott Laboratories

-Facility cleanup
- Screw Cap
- Inadequate Spun of IV Business

Hospital Procedures

- ~ 24 Hours Changeout
- Minimize IV Integrity Breach
- Avoid disrupting contents
- Never replace cap

Recommendations

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• Environmental studies at production facility
• Culture studies of closure during normal production
• Salt studies
• Fluorescent dye studies of cap assemblies

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• Inhibitor properties of cap components
• Contamination transfer from closure to fluid

Applicable
cGMPs

Sampling and Testing of In-process Materials and Drug Products.



In-process materials shall be tested for identity, strength, quality, and purity as appropriate, and approved or rejected by the quality control unit, during the production process, e.g. at commencement or completion of significant phases or after storage for long periods.

Control of Microbiological
Contamination



Appropriate written procedures, designed to prevent objectionable microorganisms in drug products purporting to be sterile, shall be established and followed.

CONCLUSION

Bottled water is regulated as a food under the FFDCA by the FDA. Specific FDA regulations in the bottled water area cover CGMPs for bottled water production and a standard of identity and quality for bottled water. Recent regulatory activity on bottled water includes adoption of allowable levels of certain disinfectants and disinfection by products in the quality standard for bottled water and publication of a feasibility study on the appropriate methods for providing consumers with information on the contents of bottled water.

REFERENCES

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• CDC. Follow-up on septicemia associated with contaminated intravenous fluid from Abbott Laboratories. MMWR 1971;20:110.
• Maki DG, Rhame FS, Mackel DC, Bennett JV. Nationwide epidemic of septicemia caused by contaminated intravenous solutions. I. Epidemiologic and clinical features. Am J Med 1976;60: 471-32.

Q & A

The End ~