diff --git a/src/sbmlsim/Batch.py b/src/sbmlsim/Batch.py
index 21e37c2..7bc211b 100644
--- a/src/sbmlsim/Batch.py
+++ b/src/sbmlsim/Batch.py
@@ -203,7 +203,7 @@ def generate(
                     number_susceptible,
                     selected_susceptible_mutations,
                 ) = self._get_susceptible_mutations(
-                    n_sus, remaining_aa_positions, sample_gene
+                    n_sus, remaining_aa_positions, sample_gene, sample_label=label
                 )
             else:
                 selected_susceptible_mutations = []
@@ -342,7 +342,9 @@ def _get_resistant_mutations(self, n_res, distribution, sample_gene):
             number_resistant,
             selected_resistant_mutations,
             selected_resistant_positions,
-        ) = self._get_defined_mutations(label="R", n=n_res, distribution=distribution)
+        ) = self._get_defined_mutations(
+            label="R", n=n_res, sample_label="R", distribution=distribution
+        )
 
         # Get amino acid positions that are not altered by selected resistant mutations
         remaining_aa_positions = [
@@ -354,7 +356,9 @@ def _get_resistant_mutations(self, n_res, distribution, sample_gene):
 
         return number_resistant, selected_resistant_mutations, remaining_aa_positions
 
-    def _get_susceptible_mutations(self, n_sus, remaining_aa_positions, sample_gene):
+    def _get_susceptible_mutations(
+        self, n_sus, remaining_aa_positions, sample_gene, sample_label
+    ):
         # choose susceptible mutations for a sample
 
         if self.define_susceptibles:
@@ -366,6 +370,7 @@ def _get_susceptible_mutations(self, n_sus, remaining_aa_positions, sample_gene)
                 label="S",
                 n=n_sus,
                 distribution="poisson",
+                sample_label=sample_label,
                 remaining_aa_positions=remaining_aa_positions,
             )
 
@@ -434,9 +439,13 @@ def _get_susceptible_mutations(self, n_sus, remaining_aa_positions, sample_gene)
         return number_susceptible, selected_susceptible_mutations
 
     def _get_defined_mutations(
-        self, label, n, distribution, remaining_aa_positions=None
+        self, label, n, distribution, sample_label, remaining_aa_positions=None
     ):
 
+        assert not (
+            label == "R" and sample_label == "S"
+        ), "Cannot have resistant mutations in a susceptible sample"
+
         if label == "R":
             mutation_positions = self.resistant_positions
             mutations = self.resistant_mutations
@@ -457,12 +466,14 @@ def _get_defined_mutations(
             while True:
                 number_mutations = numpy.random.poisson(n)
                 if label == "R":
-                    if number_mutations > 0 and number_mutations <= len(
+                    if 0 < number_mutations <= len(mutation_positions):
+                        break
+                if label == "S":
+                    if sample_label == "S" and 0 < number_mutations <= len(
                         mutation_positions
                     ):
                         break
-                if label == "S":
-                    if number_mutations > 0 and number_mutations <= len(
+                    if sample_label == "R" and number_mutations <= len(
                         mutation_positions
                     ):
                         break