I am a passionate believer in the “Law of Unintended Consequences.” And, to quote Jeff Goldblum’s character Ian Malcolm in Jurassic Park, “Just because you can do something, doesn’t mean you should do something.” One good example of “unexpected side-effects” is found in the continuous breeding of dairy cows used only for their capacity to provide milk. These cows are so docile they won’t defend their own calves—even allowing them to be slaughtered in front of their own eyes while showing no inclination to offer protection.

That may be an extreme example, but ALL changes have consequences, both good AND bad (we usually opt for the ratio that favors the good). Another obvious example is the enormously successful mail-order/home delivery business. While we have been able to order from catalogs for a century (remember the ever-present Sears catalog?) or have pizza delivered to your home, corporations like Amazon, Chewy, and Grub Hub accelerated the trend. Now, with the pandemic, ordering from home has become the norm, not the exception. On one hand this has been a blessing, allowing needed food, goods, and medicines to be obtained without exposure to the COVID virus.

However, this trend has also hastened the previously slow and steady downfall of “brick and mortar” stores and malls, in general. When large malls close, big name stores like Sears and Target can continue selling through their websites (and, ironically, through Amazon). Simultaneously, the smaller, non-chain stores, without websites or a national presence, are folding. Add to this matrix the social factor malls provide, allowing for a mixture of shopping and dining, and, for many seniors, a safe place to walk/exercise. Add all of these elements together and you have a net loss for the conveniences involved.

What does all this have to do with Pharma? In many ways—before, during, and presumably, after the pandemic—we have migrated to remote testing, virtual QA oversight, Compliance monitoring, and even (eventually) remote Agency “visits.” This mass migration to everything being done remotely has been shown to have many good features—assuming the job can be performed remotely. For example:

1. A company’s yearly/monthly savings on rent, utilities, food (assuming a cafeteria or free coffee and snacks), and maintenance services, when workers work from home, are substantial. And, since many are downsizing, rent and property taxes are diminished.
2. The QA/Compliance officers can literally visit 4, 5, 6, or 7 disparate locations within the country or multiple countries in a single week. Caseloads can now be worked through with incredible speed.
3. On average, most workers put in more actual work hours, since they no longer need to commute or leave early for doctors’ appointments, can eat lunch at their computer, or even make a quick trip to the store, without having to leave work early.
4. Employees’ transportation costs are vastly reduced: gasoline, tolls, maintenance, and even insurance are lower. The gains here are mitigated by a) more electricity use, somewhat obviating environmental gains from less gasoline being burned, b) the stress on the internet bandwidth from multiple Zoom users per household and many more movies being downloaded, and c) miscellaneous utilities—the well system in our community was stressed by so many stay-at-home parents and schoolchildren that water had to be trucked in, when the aquifer was nearly depleted.
5. With social distancing and mask-wearing and travel protocols, the flu season was remarkably mild this year. Usually, a large number of cases occur when kids begin school, come in contact with many other youngsters, and bring home the flu virus.
6. Less auto and air travel has resulted in major environmental gains. Case in point: some people in China report seeing the Himalayas for the first time, the air is so clear. Other gains include the recovery of some wild species.
7. In the corporate structure, monitoring the (remote) locations’ records (incoming materials, in-process records, and final product analysis results) has been aided by the newer computer platforms (e.g., Zoom) and new commercially available software suites, allowing them to be reviewed easily and often, even after working hours making time zone differences moot.

However, one of my go-to sayings is “no good deed goes unpunished.” This may also be re-stated as, “every silver lining has a cloud.” One of my favorite short stories by Robert Heinlein is “The Moon is a Harsh Mistress.” The flag of the colony simply says “TANSAAFL.” It means “there ain’t no such thing as a free lunch.” Likewise, as good as any technology or software or practice may be, there is always a price to pay.
Then, why would an in-person, or in today’s terms, non-virtual, contact be necessary or important? Several cases spring to mind:

1. User security. If hackers can infiltrate secure U.S. Government computer systems, it would not be all that hard to imagine corporate espionage. In the race to a COVID vaccine, knowing where the “other guy” is wouldn’t hurt, as an example. Also, thieves would love to find the delivery schedules for COVID vaccines. Imagine the “benefit” of knowing the proprietary formulation and production methodology of a competitor. Sometimes, face-to-face and written documents aren’t all that “old-fashioned” after all.
2. Understanding the problem(s). I have had to work remotely with clients in several countries. It has sometimes taken days due to time zone differences to complete a “conversation” that should have taken one hour. This especially applies to technology transfer, such as analytical or production methodology.
3. Incomplete data transfer. I don’t mean numbers, dates, or spectra, I am referring to actual “eyes-on” cooperation. This is the reason that when an analytical method was transferred from Analytical R&D to QC when I was at Sandoz, the developer of the method was not allowed to be present the first time it was tried out.
4. Interpersonal bonding. I would not be exaggerating when I say most of my full-time industrial or teaching slots were the result of meetings I attended (in vivo not in silico). For example, one time, after the Ciba-Geigy merger, I was visiting a former coworker for lunch, sitting with hiring manager. As I was leaving to return to work, he approached me with an application and offered me a job.

While millennials believe they can learn all they need form the internet (or simply by reading papers or watching videos), it is more likely they could learn more about the work by sitting across the table over coffee or an adult beverage with the author/presenter and asking “what didn’t work?” Or asking, “what are your next steps” or “what similar work have you done?”

Now, considering the extremes of “the old way” versus “totally virtual,” I would suggest either the words of the Greek poet Hesiod (c.700 BC): ‘observe due measure; moderation is best in all things’; or the Roman comic dramatist Plautus (c. 250–184 BC): ‘moderation in all things is the best policy.’ How this philosophy may be applied to the current conversation can be to find a middle ground between “meetings, meetings, meetings” and “always remote conversations.”

How do we best define the “new normal” after the worst ravages of the pandemic have passed? Clearly, we have seen enough benefits and savings from the “stopgap” measures needed to survive the quarantine to embrace them as permanent. And, since the potential for repeat and new outbreaks of pandemics in the future exists, we will most likely never go back to the “good old days.” The good or bad of that is moot. To use a phrase I personally dislike, “It is what it is.”

Considering the gains in air quality and the recovery of numerous “wild” species, there will be pressure from environmental groups to not commute or fly as much as was the norm a few years ago. Further savings in infrastructure wear and tear will result from lower loads, allowing repairs and upgrades to proceed without horrible traffic delays. Worst case, we know we can work from home to avoid congestion.

The lessened load on face-to-face inspections would allow the lower number that are actually held can be more in-depth, since the former time restrictions are not any longer a reason to hurry an inspection. This means that a problematic site can be visited more often, allowing for better control and remediation of any problems. This greater allotted time is also available for transfer of methodologies, analytical techniques, and record-keeping techniques.

Being completely honest, we need to recognize that the production sites being monitored are not all in need of the same level of scrutiny or assistance. Some of the newer start-ups are operating in developing countries with less experience with GMP requirements and/or with a lower level of experienced staff. In the old days (BC = Before COVID), the sheer number of sites needing to be inspected precluded any semblance of frequency. With virtual chats, reviews, inspections, and video observations, the less needy sites can be accessed as needed. The actual visits can be farther apart and still have control and compliance maintained. This allows inspection personnel more time to physically visit the sites where their presence is most needed.

It will be up to each organization to determine the optimum mix of virtual to hand’s-on time for each of its sites (sub-contractors, fully-owned, or whatever), since not all teams are the same size, have the same suppliers, or make the same number and batch-sized products. Some may even determine that the current, virtual model is best for them and others cannot wait to come close to the 2019 model. In either case, we now have a lot more tools to make better, safer products. 

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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.