Questions and Answers Regarding Methylphenidate Hydrochloride Extended Release Tablets (generic Concerta) made by Mallinckrodt and Kudco

What is methylphenidate hydrochloride extended-release?

Methylphenidate hydrochloride extended-release (ER) is a drug approved by FDA to treat attention deficit-hyperactivity disorder (ADHD) in adults and children ages six and older. Concerta is one brand of methylphenidate hydrochloride ER tablets. Concerta is manufactured and marketed by Janssen Pharmaceuticals, Inc. 

What are the generic versions of Concerta?

Approved generic versions of Concerta are manufactured by Mallinckrodt and Kudco. Janssen also manufactures an authorized generic of Concerta, which is marketed by Actavis under a licensing agreement. Although it is marketed by Actavis as a generic and not under the Concerta brand name, the Actavis drug is identical to Janssen’s Concerta. 

When were the Mallinckrodt or Kudco generic products approved by FDA?

Mallinckrodt received FDA approval of its abbreviated new drug application (ANDA) on December 28, 2012, for the 27-, 36-, and 54-milligram strengths. 

Kudco received FDA approval of its ANDA on July 9, 2013, for the 18- and 27-milligram strengths, and September 23, 2013, for the 36- and 54-milligram strengths.

How can patients find out which company manufactured their methylphenidate hydrochloride ER product?

Anyone with questions or concerns about where their methylphenidate hydrochloride ER product was manufactured should contact the pharmacy where the prescription was filled.

Will the generic methylphenidate hydrochloride ER made by Mallinckrodt or Kudco be taken off the market or recalled?

FDA has asked that within six months, Mallinckrodt and Kudco confirm the bioequivalence of their products using the revised bioequivalence standards, or voluntarily withdraw their products from the market. FDA has changed the therapeutic equivalence (TE) rating for the Mallinckrodt and Kudco products in Approved Drug Products with Therapeutic Equivalence Evaluations (commonly referred to as the “Orange Book”) from AB to BX.  This means that the data are insufficient to show that the Mallinckrodt and Kudco provide the same therapeutic effect as Concerta (or the authorized generic marketed by Actavis).  A drug with a BX rating is still approved and can be prescribed, but is not recommended as automatically substitutable at the pharmacy (or by a pharmacist) for the brand-name drug. 

Are other generic versions of Concerta methylphenidate hydrochloride ER available on the market?

Actavis continues to market an FDA-approved authorized generic version of Janssen’s Concerta under an agreement with the brand-name company. This product is called an “authorized generic” because it is manufactured by the brand-name company, but is marketed as a generic. The Actavis generic product is identical to Janssen’s brand-name Concerta.  FDA has not identified concerns with the Actavis or Janssen products. 

Does this action affect other currently approved methylphenidate hydrochloride ER products (e.g., Ritalin LA)?

No. This action only pertains to generic drugs that reference Concerta. It does not affect other methylphenidate hydrochloride ER products. 

How did FDA become concerned that Mallinckrodt and Kudco methylphenidate hydrochloride ER tablets may not be therapeutically equivalent?

FDA began to receive reports of lack of effect associated with the Mallinckrodt and Kudco generic methylphenidate hydrochloride ER products shortly after the initial approval of each product, in December 2012 and July 2013, respectively. Between May 2013 and June 2014, the FDA Adverse Event Reporting System (FAERS) database received reports of patients describing insufficient therapeutic effect. There were nearly 200 reports about the Mallinckrodt product and over 100 reports about the Kudco product. 

Although the total number of lack of effect reports with these two products is very small compared to the overall usage of the products, FDA evaluated the overall number of complaints for these two generic products relative to the brand-name and authorized generic products and found substantially more complaints for the two generic products – prompting FDA’s investigation into this issue.

After learning of concerns with the products, FDA’s Office of Generic Drugs conducted a multi-disciplinary review of the products, which included:

  • An evaluation of adverse event reports
  • A review of the data that were submitted with the ANDAs
  • Testing of the drug products in FDA labs, including drug stability and dissolution testing to determine the drug release rate and the stability of the two methylphenidate isomers and their degradation products
  • Broad interdisciplinary consultation with FDA physicians, pharmacists, chemists, and other agency scientists and experts to discuss the new information

Why didn’t FDA uncover this concern before approving these generic drugs?

Before approving any generic drug product, FDA requires many rigorous tests and procedures, in addition to the bioequivalence testing of the product against the reference listed drug (brand-name drug), to assure that the generic drug is substitutable for the brand-name drug. The original draft guidance recommendations for bioequivalence testing for this product (published in September 2012) were developed using the best information available at the time of issuance. This included, among other information, a comprehensive discussion of the issue by an FDA Advisory Committee on April 13, 2010.

In addition to tests performed prior to market entry, once approved, FDA regularly and thoroughly evaluates reports of alleged drug product inequivalence, such as lack of effect, as in this case. In some cases, such reports can lead to a re-evaluation of equivalence in light of new scientific approaches and methodology that have been developed subsequent to the initial draft guidance publication.

Mallinckrodt and Kudco provided data that met FDA’s approval standards at the time of approval, consistent with FDA’s best understanding of how to demonstrate bioequivalence to Concerta. The data showed the methylphenidate hydrochloride ER products to be bioequivalent to Concerta based on FDA’s understanding, at that time, of how the pharmacokinetics of Concerta contributed to the therapeutic efficacy.  

Do other generic versions of ADHD drugs on the market raise similar concerns?

At this time, there is no evidence that other generics in this class raise similar concerns. FDA will continue its monitoring of all generic drugs, and all products on the market, and welcomes any information from the public about the performance of drugs and any adverse effects. 
Is FDA going to revise testing and approval standards for the other generic ADHD drugs on the market?

The previous draft bioequivalence guidance on generic methylphenidate hydrochloride ER tablets (Concerta) recommended measuring the total amount of drug absorbed into systemic circulation from initial dosing until three hours after taking the drug and from three hours post-dosing until the last measurable time. The total amount of drug absorbed during these two time periods were thought to capture the initial immediate release of the drug as well as the extended release of the drug during the latter part of the day. Through the investigation of post-marketing reports with Concerta’s generic products, FDA determined that these recommendations should be updated to help ensure bioequivalence and support a demonstration of therapeutic equivalence.  

FDA’s understanding of the relationship between the drug release characteristics of generic versions of Concerta and their impact on therapeutic effect has evolved, and FDA has revised its draft guidance for methylphenidate hydrochloride ER (Concerta).  FDA will continue to evaluate and revise other testing and approval standards, as well as bioequivalence guidances for other generic methylphenidate hydrochloride ER products as needed. 

Is FDA going to further study generic methylphenidate hydrochloride ER products?

Studying generic methylphenidate hydrochloride ER tablets has been identified as a priority by stakeholders and FDA. Under the Generic Drug User Fee Act of 2012 regulatory science grants, FDA commissioned two studies: a bioequivalence study in healthy adult volunteers, which started in October 2014 and is expected to finish by April 2015, and a pharmacokinetic and pharmacodynamic study in children with ADHD, which started in October 2014 and is expected to finish by September 2017.

Page Last Updated: 11/13/2014
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