Baseball great Yogi Berra once said, “It’s tough to make predictions, especially about the future.”

Yogi Berra didn’t know anything about Covid-19 — he passed away five years ago — but his quote applies to the development of a Covid-19 vaccine.

Over the past six months, pharmaceutical companies have made various predictions about their Covid-19 vaccine timelines that have turned out not to be true.

In one recent example, Pfizer has said for weeks it would know by the end of October if its vaccine works or not — but Tuesday on an investor call, the company’s CEO essentially ruled that out.

GSK, Sanofi pledge 200M doses of potential COVID-19 vaccine to global alliance

While at times Pfizer and other companies have couched their statements, other times they have been more definitive about their projections.

Scientists say that should guide us as we move closer to having a vaccine: Don’t believe everything you hear, because testing and manufacturing vaccines is notoriously unpredictable.

“Unexpected things happen all the time in vaccine development,” said Dr. Nelson Michael, an Army vaccine specialist who has worked on more than 20 vaccine clinical trials. ”There are tons of twists and turns, and it’s important to understand that.”

GSK, Pfizer, other pharma CEOs pledge COVID-19 vaccines will be safe, effective

While health officials have also made forward-looking statements, they’ve typically been more vague than pharmaceutical companies.

Last week, National Institutes of Health Director Dr. Francis Collins told the National Press Club he remains “cautiously optimistic” that the United States could have a Covid-19 vaccine authorized by the end of the year, but warned “it might take longer.”

Dr. Paul Offit, a member of the US Food and Drug Administration vaccine advisory committee, said pharmaceutical companies would be wise to stop making forecasts about their timelines.

LabCorp launches new test aiming to assist COVID-19 vaccine trials

“Companies should stop making predictions, because nature is very humbling,” Offit said.

Claim of a ‘near perfect’ vaccine

In September, Ugur Sahin, CEO of BioNTech, which is working with Pfizer on its coronavirus vaccine, told CNN that his company’s vaccine is “near perfect.”

Scientists interviewed for this story shuddered at the thought of describing a vaccine as “near perfect” when it hasn’t yet been fully studied in large-scale trials. The Pfizer vaccine, as well as three others, are still in Phase 3 clinical trials in the United States, and no one knows if they work at all — let alone to near perfection.

Vaccines by Pfizer and another pharmaceutical company, Moderna, utilize a new kind of technology in their Covid-19 vaccines — no vaccine on the market has ever used it.

Offit said that alone is reason for caution.

“This virus has been around for less than a year, and it causes a variety of clinical findings that we never would have predicted, and now we’re going to counter it with a vaccine that has no commercial experience? How about a little humility here?” said Offit, a member of the FDA’s Vaccines and Related Biological Products Advisory Committee.

According to a BioNTech statement sent to CNN, Sahin’s comment was “based on preliminary antibody and T cell responses and a favorable safety profile observed in the study so far. He also noted that there is a need to wait for the efficacy data which is not available yet.”

Pfizer’s CEO has made predictions about when it will be clear if a vaccine works or not.

On September 8, Albert Bourla told the Today show that “we will have an answer by the end of October” whether the vaccine works, adding that “our model, our base case, predicts that we will have an answer in, by the end of October. Of course, this is only a prediction.”

On October 16, Bourla made a similar comment in an open letter on his company’s website, stating that “we may know whether or not our vaccine is effective by the end of October.”

But on the investor call Tuesday – just five days before the end of the month — Bourla said the company hasn’t seen its vaccine data yet. Pfizer’s first opportunity to see that data will be when 32 people in its trial become sick with Covid-19 – and Bourla told investors that this has not yet happened.

Reaching those 32 coronavirus cases will still not give the company the data it needs. An independent panel of experts will need to analyze those cases — and that can take at least a week, Bourla told investors. That means the data couldn’t come in October, as Bourla had predicted.

CNN reached out to Pfizer for a response.

“I don’t believe our CEO or we have said that the world should definitely expect an announcement at the end of the month. Rather, it’s that there was potential that we would know about efficacy by the end of the month. Nothing has changed,” according to a company spokesperson.

Predictions from the University of Oxford for September results

Pfizer isn’t the only company that’s made predictions that likely will not or did not come true.

In April, Sarah Gilbert, an Oxford researcher told The Times in the UK that she was ”80% confident” the vaccine being developed by her team would work — even though at that point Oxford had not even started their Phase 3 clinical trials.

In May, CNN asked Oxford researcher Dr. Adrian Hill when the university’s trial would end.

“My guess is July would be good. August more likely. Might be September,” he said. ”We’re aiming for September but hoping to finish before that.”

September came and went. Even now, Oxford’s Phase 3 trial is still underway.

“We have seen with this pandemic that the spread and transmission rates have fluctuated making them challenging to predict, and important measures to control cases, such as the lockdown by the UK Government, have slowed the transmission rate,” an Oxford spokesperson wrote in an email to CNN. “We have consistently maintained that if transmission remained high, we may get enough data in a couple of months to see if the vaccine works, but if transmission levels drop, this process could take longer.”

Viruses — and vaccines — are unpredictable

The spread of a virus is unpredictable — and vaccine experts say that’s exactly why pharmaceutical companies should avoid making predictions.

In the Phase 3 trials, pharmaceutical companies vaccinate study participants and then see if they become infected in the course of their daily lives. When rates of the virus go down, fewer participants will become infected, which slows down the trial.

Even after the clinical trials are completed, there can be problems with manufacturing. That’s been true for many vaccines and could be true of the Covid-19 vaccines as well.

“People don’t think about manufacturing, but manufacturing has killed a lot of products,” said Norman Baylor, former director of the FDA’s Office of Vaccines Research and Review.

Drugs typically use chemicals, but vaccines deal with growing living material, which doesn’t always go as planned.

“It’s wilder and crazier when you’re involving living systems,” Baylor said. “Manufacturing a vaccine is a lot like cooking. A recipe may work fine one day but not the next.”

That’s why vaccine experts say the best laid plans can go askew.

“The best-case scenario never happens,” said Michael, the director of the Center for Infectious Disease Research at the Walter Reed Army Institute of Research. “Bumps and warts happen in vaccine development.

Or to quote Berra once again, “it ain’t over till it’s over.”