2003D-0206 - Draft Guidance for Industry on Exocrine Pancreatic Insufficiency Drug Products--Submitting New Drug Application; Availability
FDA Comment Number : EC2
Submitter : Dr. Tibor Sipos Date & Time: 07/07/2004 05:07:54
Organization : Digestive Care, Inc.
Drug Industry
Category :
Issue Areas/Comments
PART 1 OF 10
DOCKET NO. 2003D-0206 (2003N-0205)

Digestive Care, Inc. (DCI), manufacturer of PANCRECARB (pancrelipase) Delayed-Release Capsules, wishes to comment on the proposed guidance documents for submitting NDA for Exocrine Pancreatic Insufficiency Drug Products, dated March 26, 2004.

DCI appreciates the fact that the Agency recognizes these enzyme products have been safely and effectively used for decades. At the same time, DCI fully supports the spirit and initiative captured in this document and understands FDA?s continuing role in applying rigorous scientific standards to these products while maintaining market access to all patients. We would, however, like to address several items in this guidance document that we feel need further consideration. These items could impose insurmountable barriers to implementation and could add significant cost increases without any added safety or efficacy benefits. Before addressing these comments, allow me to first provide a brief introduction.

Credentials: Tibor Sipos, Ph.D., President of DCI:

Over the past 35 years, I have been directly involved in the development of Pancreatic Enzyme Products (PEPs). I am the original inventor and developer of the pancrelipase containing enteric-coated microspheres which were first marketed in 1978 by Johnson & Johnson (Ortho-McNeil) under the trade name of PANCREASE. Also, I am the original inventor of the bicarbonate-buffered and enteric-coated pancrelipase microspheres marketed by DCI under the trade name of PANCRECARB. During the research and development (pharmaceutical and clinical) phase of these two successful products, I had the privilege and honor to directly interact with eminent clinicians in the design and establishment of clinical methodology in demonstrating the efficacy of pancrelipase products to control steatorrhea in chronic pancreatitis and cystic fibrosis patients.

In addition, I directed the enzymatic characterization of bile juices obtained from the duodenum and upper intestine of chronic pancreatitis and cystic fibrosis patients. These bile juices were collected using a triple-lumen gastrointestinal tube. During these studies, I helped to develop clinical methodologies for the demonstration of bioavailability of exogenously administered pancrelipase products in the upper intestine. More recently, I partially supported clinical research studies to determine the fate of exogenously administered enteric-coated pancrelipase products in the entire intestine of adult cystic fibrosis patients by employing a seven-lumen gastrointestinal tube with suction ports positioned in the stomach, duodenum, upper, middle and lower intestine.

It is on the basis of the three plus decades of direct involvement in research, clinical development and commercialization of these products, that I
offer the following comments on these proposed guidelines.


Chemistry, Manufacturing, and Controls Section of the Application:

 Classical biologicals are recognized in ICH guidelines as complex mixtures requiring different characterizations than highly purified biologicals.

As this section refers to various ICH guidelines, it is important to note the historical development of some of these guidelines as they pertain to ?classical? biologicals, which can be characterized as complex mixtures in contrast to highly purified products (such as rDNA). Although the original focus for these guidelines was on all biological products, experts have acknowledged that for classical biologicals, the evaluation of quality should focus on historic safety and potency. As a result, a consensus was reached to restrict the application of the guidelines to products amenable to a high degree or purity, and address the requirements for classical biologicals on a case-by-case basis.