Developing a Comprehensive Approach for Preventing Metal Contamination of Pharmaceutical Products - Pharmaceutical Technology

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Developing a Comprehensive Approach for Preventing Metal Contamination of Pharmaceutical Products
This discussion aims to outline an approach to metal contamination prevention that should achieve a level of control acceptable to all stakeholders. A three-tiered approach is described. This paper also discusses the application of engineering and procedural controls in pharmaceutical manufacturing. Practical examples to cover a variety of pharmaceutical dosage forms are included to illustrate this comprehensive approach.


Pharmaceutical Technology
pp. s6-s11

Engineering controls versus procedural controls

Two types of controls—engineering and procedural—are typically used in a comprehensive approach to elimination of metal contamination in pharmaceutical products. Engineering controls are those built into the equipment, system, or processes not directly dependent upon human interaction for success. Examples include mechanical devices, environmental controls, or computer systems. Certainly, we must include appropriate validation and qualification of these controls to ensure they are adequate and properly function. When done well, engineering controls can typically be relied upon to provide greater and more consistent performance than controls relying upon personnel performance.

Procedural controls are human based and dependent upon individuals properly performing tasks defined in standard operating procedures, batch records, work instructions, or other controlled documents. Some of the keys for successful procedural controls include a clear and understandable procedure, effective training, and motivated employees following procedures with discipline.

Engineering controls cannot be applied to every manufacturing activity. However, processes can be perfected to the extent possible. The use of color-coding, poke yoke practices, and applicable verification systems can minimize non-adherence.

Conclusions

The control and prevention of metal contamination in pharmaceutical products is a challenge from all perspectives—regulatory, safety, and manufacturing. It is clear that visible metal particles are unacceptable. Control of metal contamination cannot be readily achieved with a single-pronged approach. We must employ a multifaceted, comprehensive approach to ensure a sustainable performance for prevention of metal contamination. This approach must include intentional prevention activities, in-process control or removal and, ultimately, detection as a final safety net. Any approach that does not include all three facets will likely yield unacceptable results over the long term. It is also important to understand that both engineering and procedural controls must be employed along with formal oversight (e.g., validation, qualification, training, verification, effectiveness, and documentation).

By enhancing our overall control strategy to include this comprehensive approach, we should expect success in the control of metal contamination of our products.

Lorraine Mercurio is a project manager in the Product Supply organization of Mallinckrodt, the Pharmaceuticals business of Covidien in St. Louis, Missouri.

Eldon Henson* is Director, Operations Technical Services at Mallinckrodt and serves as President of the Missouri Valley Chapter of the Parenteral Drug Association (PDA).

*To whom all correspondence should be addressed.

References

1. FDA, 21CFR211.67, (a) "Equipment, cleaning, and maintenance," 43 Federal Register 45077, Sept. 29, 1978, as amended at 73 FR 51931 (Sept. 8, 2008).

2. FDA, 21CFR211.84, 43 Federal Register 45077, Sept. 29, 1978, as amended at 63 FR 14356, Mar. 25, 1998; 73 FR 51932 (Sept. 8, 2008).

3. ICH, Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, November 2000.

4. FDA, Compliance Program Guidance Manual, CPGM 7356.002.

5. USP, Chapters <1> <788>, <797>, United States Pharmacopeia/National Formulary.

6. FDA, Warning letter to Berlex Laboratories (March 11, 2002), http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2002/ucm144810.htm accessed 12/329/11.

This article was originally published in the Journal of GXP Compliance, 16(1), 51-56 (Winter 2012).

For related article, see also "Elemental Impurities" in the Nov. 2012 issue of Pharmaceutical Technology.


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