[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2008]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR310.543]

[Page 36]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF 
 
PART 310_NEW DRUGS--Table of Contents
 
        Subpart E_Requirements for Specific New Drugs or Devices
 
Sec. 310.543  Drug products containing active ingredients offered 
over-the-counter (OTC) for human use in exocrine

pancreatic insufficiency.

    (a) Hemicellulase, pancreatin, and pancrelipase have been present as 
ingredients in exocrine pancreatic insufficiency drug products. 
Pancreatin and pancrelipase are composed of enzymes: amylase, trypsin 
(protease), and lipase. Significant differences have been shown in the 
bioavailability of marketed exocrine pancreatic insufficiency drug 
products produced by different manufacturers. These differences raise a 
potential for serious risk to patients using these drug products. The 
bioavailability of pancreatic enzymes is dependent on the process used 
to manufacture the drug products. Information on this process is not 
included in an OTC drug monograph. Therefore, the safe and effective use 
of these enzymes for treating exocrine pancreatic insufficiency cannot 
be regulated adequately by an OTC drug monograph. Information on the 
product's formulation, manufacture, quality control procedures, and 
final formulation effectiveness testing are necessary in an approved 
application to ensure that a company has the ability to manufacture a 
proper bioactive formulation. In addition, continuous physician 
monitoring of patients who take these drug products is a collateral 
measure necessary to the safe and effective use of these enzymes, 
causing such products to be available by prescription only.
    (b) Any drug product that is labeled, represented, or promoted for 
OTC use in the treatment of exocrine pancreatic insufficiency is 
regarded as a new drug within the meaning of section 201(p) of the 
Federal Food, Drug, and Cosmetic Act (the act), for which an approved 
application under section 505 of the act and part 314 of this chapter is 
required for marketing. In the absence of an approved application, such 
product is also misbranded under section 502 of the act.
    (c) Clinical investigations designed to obtain evidence that any 
drug product labeled, represented, or promoted for OTC use in the 
treatment of exocrine pancreatic insufficiency is safe and effective for 
the purpose intended must comply with the requirements and procedures 
governing the use of investigational new drugs set forth in part 312 of 
this chapter.
    (d) After May 7, 1991, any such OTC drug product that contains 
hemicellulase initially introduced or initially delivered for 
introduction into interstate commerce that is not in compliance with 
this section is subject to regulatory action.
    (e) After October 24, 1995, any such OTC drug product that contains 
pancreatin or pancrelipase initially introduced or initially delivered 
for introduction into interstate commerce that is not in compliance with 
this section is subject to regulatory action.

[60 FR 20165, Apr. 24, 1995]