Watching the conflict in the Ukraine, it becomes obvious that hardware alone does not win a battle. Flexibility and morale count quite a bit too. In addition to some technology suggestions, I want to look at personnel hints.

My wife has been working from home on Fridays for years. (Normal NY/CT traffic mixes with vacation traffic and the multi-hours spent in a car could better be used working.) Since she does sensitive contract work, they gave her a VPN (Virtual Privacy Network) account to use. So, when the COVID lockdown happened, all their personnel had to work from home. In fact, there is a chance they will never return to a full-time office environment.

What does this have to do with Pharma work? Well. I used to joke that, when I first started (spoiler alert: GMP didn’t exist then), we used to work in the lab from Monday morning till Friday lunchtime, then write up all our lab data and reports. Under GMP (or, QA’s interpretation of GMP), we did lab work on Monday and spent the next four days writing. That may be an exaggeration, but not that far a stretch.

Several years ago, a colleague wanted to get caught up on paperwork, so took her notebook home to write up her results and was almost terminated for taking “controlled data” off company property. Now, with the availability of electronic notebooks, safe “cloud” computing, and VPNs, much “busy” work can easily be accomplished from home. This is especially true for jobs that are largely paperwork, namely Quality Assurance, business reports, sales, clinical trial data-crunching, NDA or ANDA submissions—the bulk can be done from a remote location.

There would be a number of benefits from allowing employees to use remote connections:

1. The office area could be reduced, saving on electricity and HVAC requirements.
2. The flexibility of home workers would allow, for example, for a doctor’s visit or child care without them having to take days off. This should increase “time on the job.”
3. The cost of gasoline and car care would decrease for employees, taking pressure off management to increase wages faster than planned.
4. Meetings, often not necessary, could be planned through a company-owned Zoom or other account. This would allow employees to discuss and share information, yet cut down on travel time (either walking to another building or having to drive from another facility) for the meeting. Better still, it would make management focus on the need for each meeting.
5. The relaxed stress levels would likely reduce turnover of personnel, looking for “greener pastures” at another job.

To implement this culture, the company might need to give a subsidy to employees to upgrade their internet service and possibly supply laptops, but those costs would be far outweighed by the savings on infrastructure expenses. It would also serve as an impetus to upgrade IT security, especially with the large increase in cyber crimes (information stealing, ransomware, etc.).

Electronic notebooks

This is something we examined at my last job. The newly made devices had some potential disadvantages. Mainly, there were far fewer WiFi-equipped labs at the time. WiFi is now ubiquitous in as diverse locations as shopping centers, homes, restaurants, and, yes offices and labs.

There was also the concern for security/confidentiality. The signals could, it was thought, be read by third parties and VPNs were not available. As for the former, I recognized a solution by accident. When the company coated the windows with a metallic-doped covering to aid the A/C, no one could get a cell phone signal. They had, in combination with the steel frame of the building, created a Faraday cage, impervious to radio signals. Ta-da! Instant security. Also, we now routinely use VPNs as the primary source of security.

Why e-notebooks? Transcription errors are more common than one would imagine. Most lab instruments (e.g., electronic balances) have the option of directly inserting the mass into the “book.” Coupled with a bar-code reader, the identity and weight of a substance would always be correct. Making it simple to have the notebook on hand will preclude the use of writing numbers on slips of paper and later entering them into your notebook—a GMP violation, by the by.

Methodology for cleaning validation

Currently, all equipment used for manufacturing dosage forms needs to be dismantled, washed and dried, and inspected for any residues before using for the next product. This is especially onerous for a contract manufacturer for two reasons: 1) they seldom have massive numbers of “extra” equipment, so they need to wait for the green light on the equipment just used before proceeding, and 2) current methods require hands on in both production and QC departments and are quite time consuming. Often, a large percentage of manufacturing equipment is down for cleaning or waiting for cleaning tests to return.

Yes, there is a better way, or why would I have even brought this topic up? Anyone who has flown in the U.S. has come in contact with an Ion Mobility Spectrometer (IMS). This is where a TSA agent swabs your hand, briefcase handle, or carry-on with a small piece of cloth and places it on a device near the exit.

This sample swab is warmed, evaporating the organic molecules and the fumes move through the chamber: the molecules are ionized (given a negative charge, usually) “softly,” so as to not fracture the molecule, and propelled down the chamber by a negatively charged grid (repulsion). The molecules all acquire a single charge and move by their charge/mass ration—smallest ions arrive at the end grid first, followed by the others, according to mass. They strike a collector and generate a voltage, proportional to the number of ions striking it.

The mechanism is similar to time-of-flight mass spectrometry (TOF-MS), but a gentle backwash of ambient air flows against the flow of sample, spreading the groups of molecules and giving a pseudo long flight path, allowing for separation. This obviates the need for an expensive high vacuum pump, needed for “true” Mass Spectrometry, making maintenance and operating expenses lower.

Even better…

Ultimately, moving to continuous manufacturing (CM) would obviate the need to dismantle and clean each unit between products. Since the major benefit of CM is time and labor saved, traditional GMP cleaning validation is a mill-stone around production’s neck. An idea occurred to me a few years back: why not use the example of an old-time mortar and pestle?

How is that helpful? We didn’t clean the mortal with water or solvents, since the open-pored porcelain would retain the moisture and make matters worse than not cleaning. Instead, we ground several portions of a dry salt (e.g., NaCl) until whatever chemicals were in the mortar were removed. I postulated that a similar approach to CM would consist of running a pure excipient, common to the just finished product and the subsequent product (e.g., lactose), through the assembled CM unit until it was clean. Clearly, this process would need to be validated before implementation, but then the CM unit would only need to be disassembled for maintenance or component replacement.

---

Emil W. Ciurczak
DoraMaxx Consulting

Emil W. Ciurczak has worked in the pharmaceutical industry since 1970 for companies that include Ciba-Geigy, Sandoz, Berlex, Merck, and Purdue Pharma, where he specialized in performing method development on most types of analytical equipment. In 1983, he introduced NIR spectroscopy to pharmaceutical applications, and is generally credited as one of the first to use process analytical technologies (PAT) in drug manufacturing and development.