Monday, May 29, 2017

Push Notification Programs Monitor Your Equipment So You Don’t Have To

By Korben Knudson

Push notifications deliver information to the end user in real time.  Since no active thinking is required to receive information in this format, the recipient may focus on other tasks at hand.  This enables push notifications to be a more efficient method of receiving information, provided you’re selective when choosing the information you want pushed.  To create a more efficient, user-friendly laboratory, RMC has adapted the push notification concept by developing software for our ÄKTA chromatography system that will text us (and our team and/or client) as our run progresses, and more importantly, will tell us when there’s a problem.

Identifying sources of inefficiency in manufacturing can be as simple as reading a Gantt chart; for a research and development laboratory it is not so easy.  Consider the inefficiencies of R&D in terms of Lean waste or muda[1].  Muda is a Japanese word meaning “futility, uselessness and wastefulness”.  In the pharmaceutical industry, it is created by under-utilizing talented scientists, under‑utilizing equipment and poor time management or experiment failures. 

Not all experiment failures are considered muda, though.  In many respects, it is also efficient to know what does not work[2].  However, perpetuating the same errors and babysitting laboratory equipment are not considered “acceptable” failures.  They are instead an especially frustrating type of R&D muda.  For example, wasting an injection because the system shut down due to a high-pressure alarm is NOT an acceptable failure.  This is muda and costs the scientist time and materials.

The adverse effects of muda are augmented as the number of stakeholders in the research increases or as the efficiency of the communication between said stakeholders decreases.  Today, many companies or teams operate in a virtual environment where transparent and effective communication is essential in order to be efficient.  There are challenges in keeping the team informed in real time, especially when members are located in different time zones or belong to separate companies.  Companies choosing a new contract manufacturing organization (CMO) are advised to consider the ability of the CMO to communicate effectively[3].  For CMOs, several stakeholders may be waiting for the results of a run and become impatient.  The client waiting for an update can also experience the same stress.  Thus, even waiting to hear about the successful experiment completion can create muda.

ChromaNotify®­­, an automated push notification system developed by RMC for ÄKTATM users, is a chromatography event monitoring program that sends the basic run information directly to a mobile phone or phones.  The software sends a text message to a list of phone numbers when certain events occur such as a high-pressure alarm, successful run completion, end of product elution, etc.  The text messages also include the date and time of the event.  After implementing the automated notification system into their chromatography systems, users performing an average of 14 chromatography runs per month (with 21% of those runs issuing an alarm) saved an estimated 2.6 hours for every alarm event by reducing the response time between the alarm issuance and the alarm acknowledgement.  Users also checked on their runs 60% less often and reduced their worry level (scaled from 1-10) by 48% after implementing the chromatography notification software[4].

Figure 1.  Examples of SMS notifications from ChromaNotify®.

Using an automated notification system, the analyst or technician no longer needs to babysit or constantly remember to check on the status of a run.  Systems like ChromaNotify® can notify the entire team simultaneously at the end of a critical step, indicating that it’s time to corroborate and discuss the results.   Thus, a company can implement Lean and Six Sigma into their R&D by eliminating wasted time and reducing the stress from worrying about and constantly checking on a run.

These systems may also be used to increase the transparency of CMOs.  From personal experience, RMC has found the frequent use of email chains a poor method of communication during a project[5].  The contract giver (i.e. the party outsourcing work) will know the progress of a project without having to frequently bother the contract receiver.  Whether the notifications report good or bad news regarding the run, all stakeholders are instantly aware and can adjust schedules, meetings, etc.  Automated push notification programs like ChromaNotify® decrease muda and increase transparency. 

[1] Benson, R. and Kulkarni, N.S.  2011.   Understanding Operational Waste from a Lean Biopharmaceutical Perspective. Pharmaceutical Engineering.  31(6).
[2] Marcus, A., Oransky, I. 2016.  Why scientists should learn to fail, fast and often.  STAT. [12May2016; accessed 29Jul2016].
[3] Choi, L., & Rudge, S.  2010.  10 Steps for Choosing a Contract Manufacturer.  BioProcess International.  8(8): 20–28.
[4] Knudson, K.; Rudge, S.  Automated Push Notifications for Column Chromatography Increase Efficiency, Productivity and Decrease Stress.  Proceedings of the 2017 Society for Laboratory Automation and Screening Conference, Washington, D.C., February 6-7, 2017.
[5] Rudge, S.  2016.  Can’t See Your Team? [blog].  RMC Pharmaceutical Solutions Blogspot.  [accessed 05Apr2017].

Monday, March 17, 2014

Modeling of the Heat Inactivation of the Coronavirus Porcine Epidemic Diarrhea Virus

by Dr. Ray Nims

A new variant of porcine epidemic diarrhea virus (PEDV, a member of the enveloped virus family Coronaviridae) has been circulating within the United States since 2013 and as of the end of January 2014 has been reported in 23 states. Due to the relatively high mortality rate caused in swine, this virus is causing severe economic losses. Mitigation of the risk of spread of this virus during husbandry and transport of livestock is of relatively great importance to the pork industry.

Thomas et al. (2013) examined the combination of temperature and time required to inactivate PEDV in swine feces on a metal surface. These conditions were investigated as possible options for livestock transport trailer decontamination when washing and disinfecting are not otherwise possible. Their results are shown in the table below. A 10-minute exposure to temperatures below 160 °F (~71 °C) failed to result in complete inactivation of the virus. As mentioned in the Thomas et, a 10-minute treatment at a temperature of 160 °F resulted in complete inactivation, as indicated by their pig bioassay, although this temperature was stated to be impractical for routine disinfection due to both cost and adverse impact on the equipment being sanitized.

While intermediate temperatures between 160 °F and 145 °F (~63 °C) were not examined empirically by Thomas et al., it is possible that a temperature lower than 160 °F might retain sufficient effectiveness to be useful for the purpose of sanitizing transport trailers. The relationship between time required for heat inactivation of viruses and temperature is essentially a power function (not a linear function). One may take advantage of this fact in modeling the time required for 1 log10 inactivation (the so-called decimal reduction value, or D) at various temperatures if one has empirical data for at least three temperatures. Since heat inactivation often displays first-order kinetics with respect to time, knowing the D value for a virus allows one to estimate the log10 inactivation after a fixed period of time (e.g., 10 minutes) at temperature. Heat inactivation data including D values at three temperatures were not found specifically for PEDV, but such data do exist for three other coronaviruses, including two from the same Genus (Alphacoronavirus) as PEDV, namely canine coronavirus and transmissible gastroenteritis virus, and one from the Torovirus Genus, namely Berne virus.

The figure below represents modeling of heat inactivation of coronaviruses in a liquid matrix caused by 10 minutes exposure to various temperatures. Since it is not known which of the two Alphacoronaviruses represent the best model virus for PEDV, modeling was also done based on the average D values for canine coronavirus and transmissible gastroenteritis virus (see line labeled Alphacoronavirus). Heat inactivation can very matrix-dependent, and the rate of inactivation of viruses in swine feces may not be represented accurately by these data for a culture medium matrix. However in the absence of specific data for PEDV in feces, the plots below may be used as an estimate of the temperature/time requirements for PEDV inactivation. If PEDV inactivation is similar to that reported for canine coronavirus, 10 minutes heating at 68 °C (~154 °F) may afford sufficient inactivation. If the data for porcine transmissible gastroenteritis virus are, however, more typical of that for PEDV, then 10 minutes heating at temperatures lower than 160 °F (71 °C) will probably fail to lead to complete inactivation. 

There is always the option, however, of increasing the exposure time from 10 minutes to, say, one hour. As shown below for the “average Alphacoronavirus” one hour heating at 63 °C (~145 °F) is estimated to result in >8 log10 inactivation.
 Perhaps these modeling estimates can guide the way for additional empirical studies to assay the effectiveness of this intermediate set of temperature/time conditions for mitigating PEDV risk during swine transport.