I have a few tips for dealing with that large of a cast, take em or leave em at your discretion:
1) For smaller characters (the squirtle, bulbasaur etc of the series) make sure they have "breathers". Don't try to force them into every episode, or people will not pay attention to them when they Do deserve the spotlight.
2) Make sure that each character (large and small) has a coherent arc of their own. Large characters may have multiple arcs, or even multiple arcs going on at a time, whereas smaller characters' arcs may be nearly forgotten about by the time you pick them back up, but the audience should be left feeling "that's right, that's what was going on with him", and you should be able to easily reference their continuing characterization and growth by merely referencing the last point in their arc. What I really mean by this is, don't introduce an element for a character then forget about it. If it's the last thing that happened to them, it should be the next thing referenced the next time we see that character.
3) Use their interactions to demonstrate the growth and depth of the characters. You should have a foil (or more) for each character, and highlight the interaction between foils. Moreover, by doing so, you make it easy to demonstrate character growth by changing who is a foil for them. Doing so should not be an arbitrary thing, it should be a logical extension of the characterization you've been doing, but done right, it is one of the easiest ways to highlight how different a character is 3/4 of the way in vs 1/4 of the way in.
4) Assess how large of a role you want each character to play early on, and don't give them more than their screen time will be able to handle. Having a squirtle of the story have 4 foils and 12 simultaneous character arcs is a terrible idea, as it will come across as muddled and no one will remember (or care) what was going on with him. When in doubt, err on the side of caution, as simplicity can be more impactful anyway. If a characters role naturally grows, sure, expand on the complexity of his presentation When their increased presence deserves it, but don't force yourself into trying to increase someone's role artificially because you started more than you could finish.
5) Remember, it can wait. With that long of a show, nothing is urgent. If you have a cool idea or tone you want to introduce, but there is still something going on in a current arc, let the arc conclude before introducing it. If you're going to be bound by geography, don't cheat, just have them spend more time in their current area to finish the arc and then move on. Pokemon actually did this really well (all the times getting lost).
6) Make sure not to write someone into a rut. If someone's been the "attack first, ask questions later" kind of person, and it's become a significant pattern, the next time they're involved in the story should be a lesson in why attacking first isn't always the best idea, and teaches them the friends they can gain by taking the time to get to know people. It breaks them out of their 1-dimensional mold, and demonstrates character growth at the same time, and it comes across as a moral of the story, not as a writing technique, which is doubly handy. Just don't let them slide right back into that rut, or the rut on the other side (the next time that character is used, in the example above, they should focus on making friends based on the lesson they learned- it reminds people of their last arc, and reinforces that they've grown. That shouldn't be an every time thing, though, you don't want them to fall into a rut as the making friends person, as that's really no better at all).
7) Plan ahead! Goes without saying, but know who's going to leave, and make sure they are a large enough presence for them leaving to mean something. Use those opportunities to reinforce the character of the smaller cast members, as well- choose a few and have earlier episodes focus on their interaction with the character in question, so after they leave the next arc for those characters can deal with their emotions and reaction to the character leaving. Plan a major challenge or setback, and walk them into it starting several episodes ahead of time, so people can think they're clever for seeing it coming, and it makes more of an impact when it happens.
8) Have logical character progression. Avoid the "as powerful as they need to be" foible, and don't have them fight people who are overly powerful or who should be incredibly difficult to beat early on, as it makes future challenges against less spectacular opponents not believable in presenting any kind of challenge. Rather, have the strength of their opponents a backdrop against which the growth of the character can be measured. Speaking of which,
9) Don't be afraid to have them lose. Winning loses all meaning eventually if there is no real risk of losing. What's more, you lose all sense of their actual level of power if there's nothing to compare it against (as no one can beat them). Having specific opponents (especially those making cameos who you intend to feature later) kick their butt, and NOT taking the cop out of having them immediately turn around and beat them, adds all the more to the impact of the characters eventually winning against them.
Sorry it's not a clean 10, hope that helps at least a smidgen, and best of luck!
