Potent Compound Containment Validation and Surrogate Monitoring

As active pharmaceutical ingredients (API) become more and more potent, the need for the validation of engineering controls and containment devices becomes imperative, and containment validation is a critical component of any potent compound safety program. Containment validation can be performed using a variety of methods, however, the most common method is to mimic the actual process using a substitute or surrogate compounds such as lactose, naproxin, or naproxin sodium.

Preventing Occupational Exposure to Active Pharmaceutical Ingredients

Active Pharmaceutical Ingredients (APIs) with occupational exposure limits (OELs) less than 10 microgram/cubic meter as an 8-hour TWA are typically considered to be potent compounds. Prevention of occupational exposure to these compounds must rely upon effective engineering controls such as powders weighing enclosures, glove boxes, hard and flexible containment, down draft booths, and local exhaust ventilation. Despite significant expenditure and effort on the installation of these controls, many of these controls fail to achieve the desired results. The cause of this failure varies, but in many cases it is due to inadequate procedures and training to ensure that the equipment is used as intended. Containment validation monitoring is an invaluable tool in not only determining proper equipment installation, but also in identifying weaknesses in administrative procedures.

Advantages of Surrogate Monitoring

The advantages of using surrogate monitoring include:

  • Works well for early stage compounds, when an industrial hygiene method has yet to be developed.
  • Relatively low toxicity of the surrogate compounds, thus allowing manipulation of equipment without posing a health risk to employees.
  • Works when the cost of the actual development compound is high.
  • Works well for contract manufacturing organizations (CMOs) where a large number of different compounds may be handled and development time lines are short.
  • Uses typical industrial hygiene equipment and methods.
  • Sensitive limit of detection/limit of quantification.
  • Numerous industrial hygiene laboratories with analytical capabilities for the surrogate compounds.

Disadvantages of Surrogate Monitoring

The disadvantages of using surrogate monitoring include:

  • To achieve the best results, requires that the actual process be performed with the surrogate compound instead of the actual API, and in many cases must be replicated several times to ensure repeatability of results.
  • Surrogate compounds may behave differently than the actual compound due to differences in static properties, moisture content, or particle size.
  • Risk of possible erroneous results due to contamination from surrogate compounds previously used in a given facility.

The implementation of a surrogate monitoring program requires expertise in development of testing protocols for each specific type of equipment to be tested. To ensure consistency of results, standardized protocols such as those published by the International Society for Pharmaceutical Engineering (ISPE) should be utlized. Affygility Solutions has significant experience in developing containment validation protocols and performing surrogate monitoring. In addition, Affygility Solutions has a web-based potent compound safety management tool called PCSSAT (potent compound safety self-assessment tool). This tool allows biotechnology and pharmaceutical companies the ability to assess the robustness of their potent compound safety program. For more information please contact Dean M. Calhoun, CIH at dcalhoun@affygility.com or visit our website at www.affygility.com.


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About Dean Calhoun

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Dean is the President and CEO of Affygility Solutions. Affygility Solutions provides environmental, health and safety software, potent compound safety, industrial hygiene, containment validation services to the pharmaceutical, biotechnology, and medical device industry. "Dean's Google+ Profile"

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