Objective
For many products, generic markets are very mature, with aggressive competition driving down the price of products for manufacturers. Under these conditions, manufacturers may not have an ability to invest in high-quality manufacturing processes.
Method
We acquired samples of all available methylphenidate products in immediate-release tablet (IR), extended-release tablet (ERT), and extended-release capsule (ERC) formulations in all available doses from all available labelers listed at one major wholesaler in February 2023. Products were analyzed for variations in dissolution parameters and for the presence of N-nitroso-methylphenidate. Finally, we examined the cost and quality of tested products.
Results
All immediate-release methylphenidate products had similar dissolution profiles. For extended-release products, the confidence intervals of the difference factors for 12 of the 24 generic extended-release tablets sampled did not contain the null value, indicating a statistically significant difference in dissolution from the branded product. N-nitroso-methylphenidate, a probable human carcinogen, was detected above regulatory thresholds in generic immediate-release products for 7 of the 15 unique products sampled. N-nitroso-methlyphenidate was detected below regulatory thresholds in extended-release tablets and was not detected above the limit of quantification in extended-release capsules. The average prices for products with and without elevated N-nitroso-methlyphenidate were not significantly different.
Conclusion
Independent laboratory testing of generic methylphenidate products found significant product quality concerns. Making product quality transparent could offer the potential to dramatically improve the quality of generic drugs at no additional cost.