The US Food and Drug Administration (FDA) has published a new final guidance document on the criteria that sponsors of new and abbreviated drug applications (NDA/ANDA) should use to evaluate tablet that have been scored to allow for the product to be split into two or more pieces.
Many products have scoring marks to allow consumers or their healthcare practitioners to split a tablet, thereby allowing the consumption of the product at controlled, lower doses without requiring multiple drug applications for each dose.
The markings themselves are seen as important enough to potentially hold up the approval of a generic product if its reference listed drug-the NDA it claims equivalence to-changes its scoring patterns. "Although there are no standards or regulatory requirements that specifically address scoring of tablets, the Agency recognizes the need for consistent scoring between a generic product and its RLD," FDA explained.
This allows for consumers to be switched between the original and generic versions of the product freely, FDA writes in the guidance. "In addition, consistent scoring ensures that neither the generic product nor the RLD has an advantage in the marketplace because one is scored and one is not."
That's the theory, anyway.
In practice, FDA has frequently raised concerns that some manufacturers are arbitrarily changing their scoring practices for the purposes of delaying generic competition. In February 2012, for example, the agency rebuffed an attempt by Warner Chilcott to delay generic competition for its Doryx acne pill. The company had changed its single-scored tablet to a double-scored tablet, and subsequently filed a petition to forced generic pharmaceutical manufacturer Mylan to do the same.
FDA denied that citizen petition on 8 February 2012, saying that it does "not agree that approving an ANDA for a generic single-scored 150 mg doxycycline hyclate delayed-release product would raise any new public health concerns, especially if the single-scored Abbreviated New Drug Application ANDA product, like your single-scored tablet, will be marketed concurrently with the double-scored product only for a finite period of time."
"There is no statutory or regulatory requirement that generic drugs have the same scoring configurations as their RLDs," FDA added.
Final Guidance Reflects Safety Concerns
This isn't to say that FDA doesn't still have concerns that need to be evaluated. "In some cases, there are possible safety issues, especially when tablets are not scored or evaluated for splitting," FDA explained in its final guidance.
Tablets that are improperly evaluated could face issues with the tablet's contents, its weight, disintegration, stability and dissolution, all of which can affect patients.
To address these concerns, FDA said its guidance reflects "consistent and meaningful criteria by which scored tablets can be evaluated and labeled."
FDA's criteria are divided into three parts:
- a harmonized approach to chemistry, manufacturing and controls (CMS) review of scored tablets
- consistency of the terms used to describe and label scored tablets
- information contained on the product labeling for use by healthcare providers
The guidance reflects a number of points that manufacturers must take into account before scoring a product.
For example, the smallest unit of a scored tablet must not be less than the minimum therapeutic dose indicated on the approved labeling. The split tablet must also be safe to handle and should have the same release features and general stability qualities as the full product. FDA explained that a risk assessment should be provided to justify results and test criteria and on no fewer than 12 individual split tablet portions. The US Pharmacopoeia's <905> Uniformity of Dosage Units standard is useful for conducting some of these tests, FDA said.
RLD vs. Generic: Is Scoring Important?
One interesting part of the guidance: FDA recommends that the "scoring configuration of generic drug products should be the same as the RLD, noting that in its 1995 Manual of Policies and Procedures Scoring Configuration of Generic Drug Products (5223.2).
That MPP notes that, "If the scoring configuration of the exhibit batch does not match that of the listed drug, the generic firm will be requested to provide a commitment, prior to the application's approval, not to market the product until it is correctly scored."
This recommendation seems to run contrary to FDA's finding in the Warner Chilcott/Mylan petition.
FDA's guidance also notes that new products meeting the criteria for scoring should be labeled as having "functional scoring," and labeling to that effect should appear in the "Dosage forms and strength" section of the highlights and full prescribing information sections of the labeling. In addition, the "How Supplied" section of the full prescribing information should also contain scoring information.
"In this way, the use of the term functional scoring in the labeling can communicate to healthcare providers that the product has been evaluated against the established criteria," FDA concluded.