Hmm, this is a difficult question. 50 characters sounds like an awful lot to get to know and remember. If they are all relevant in some way to the story/gameplay, I feel like it would get confusing or tedious. And if they are not relevant ... why put them in in the first place?
For example, let's say every character has a certain gameplay element assigned to them, like different battle styles, or some sort of ability that is necessary to the plot. At around 50 characters, I personally would run out of ideas halfway through and I feel like the game would be just a constant string of introducing new gimmick characters who are, in essence, forgettable.
Of course there's games like Pokemon, where you have literally hundreds of "protagonists", but those games are specifically built around collecting them, and they don't get any character development or anything. Also, you can only have 6 at a time in your team, so you can kind of focus on your favourites and won't really need to worry about more than those. In my opinion, way too many Pokemon have been introduced by now, which indeed makes so many of them interchangeable and negligible. Cutting down the "cast" by at least half would not do any harm at all.
If you are aiming to make a game with characters who have an interesting personality and whom the player will form an emotional bond with, they will need screentime for their character development, and therefore the more characters, the longer the game will need to be. With so many characters, you could fill multiple novels, so I can only imagine how that would translate into game time. Also, the plot will need to be more complex, and at some point it could become bogged down with all the character development.
So I guess what I'm hinting at here is, yes, you could design a game around so many characters, but I would advice against it. There are most likely many characters that could simply be combined into one or left out completely without taking away from the plot. When I started working on my current project, the party had more than 10 characters, but now I cut them down to 6 permanent ones and even that I feel is almost too many. The plot and gameplay didn't suffer any from getting rid of those "fluff" characters.
I'm mostly looking at this from a writer's and player's point of view, by the way. It's possible that different rules apply for video games in which story and character development is not very relevant, but personally, I don't enjoy those games as much.