This study investigates a new variant of the pickup and delivery problem with time windows (PDPTW) applied in cold chain transportation, which quantifies the effect of time on the quality of perishable products. Multiple commodities with incompatibility constraints are considered, where some types of products cannot be transported in a vehicle simultaneously due to their different properties and requirements for storage temperatures. The aim is to determine vehicles’ pickup and delivery routes as well as their departure times from the depot such that the travel cost and refrigeration cost of vehicles and the quality decay cost of products are minimized. We formulate this problem as a set partitioning model, which is solved exactly by a tailored branch-and-price (B&P) algorithm. To tackle the asymmetry issue arising from the pricing problem of the B&P framework, we develop a novel asymmetric bidirectional labeling algorithm. Benchmark instance sets based on real-world statistical data and classic PDPTW instance sets are first generated for this problem. Numerical results show that our B&P algorithm can solve most instances to optimality in an acceptable time frame. Moreover, our results demonstrate that integrating the refrigeration and quality decay costs into the objective function can significantly lower the total cost of cold chain transportation activities, compared to the widely adopted objective function minimizing only the travel cost.