Notice2022-08740
Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Containing an Anticholinergic or Antispasmodic in Combination With a Sedative, and Single-Entity Antispasmodic Drug Products, in Oral Dosage Form; Withdrawal of Hearing Requests; Final Resolution of Drug Efficacy Study Implementation
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
April 25, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing that all outstanding hearing requests regarding drug products containing an anticholinergic or antispasmodic in combination with a sedative, and single-entity antispasmodic drug products, in oral dosage form, under Docket FDA-1975-N-0336 (formerly 75N-0184) (DESI 10837) have been withdrawn. Therefore, shipment in interstate commerce of any such product identified in Docket FDA-1975-N-0336 covered by DESI 10837, or any identical, related, or similar (IRS) product, that is not the subject of an approved new drug application (NDA) or abbreviated new drug application (ANDA) is unlawful as of the date of this notice. This notice does not affect products covered by DESI 597 under the same docket.
Full Text
<html>
<head>
<title>Federal Register, Volume 87 Issue 79 (Monday, April 25, 2022)</title>
</head>
<body><pre>
[Federal Register Volume 87, Number 79 (Monday, April 25, 2022)]
[Notices]
[Pages 24311-24313]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-08740]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-1975-N-0336 (formerly 1975N-0184)]
Drugs for Human Use; Drug Efficacy Study Implementation; Oral
Prescription Drugs Containing an Anticholinergic or Antispasmodic in
Combination With a Sedative, and Single-Entity Antispasmodic Drug
Products, in Oral Dosage Form; Withdrawal of Hearing Requests; Final
Resolution of Drug Efficacy Study Implementation
AGENCY: Food and Drug Administration, Health and Human Services (HHS).
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
that all outstanding hearing requests regarding drug products
containing an anticholinergic or antispasmodic in combination with a
sedative, and single-entity antispasmodic drug products, in oral dosage
form, under Docket FDA-1975-N-0336 (formerly 75N-0184) (DESI 10837)
have been withdrawn. Therefore, shipment in interstate commerce of any
such product identified in Docket FDA-1975-N-0336 covered by DESI
10837, or any identical, related, or similar (IRS) product, that is not
the subject of an approved new drug application (NDA) or abbreviated
new drug application (ANDA) is unlawful as of the date of this notice.
This notice does not affect products covered by DESI 597 under the same
docket.
DATES: This notice is applicable April 25, 2022.
ADDRESSES: For access to the docket to read background documents or the
electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff (HFA-305), 5630
Fishers Lane, Rm. 1061, Rockville, MD 20852. The most relevant
background documents regarding this matter are available in the docket.
However, additional background documents are available upon request
(see FOR FURTHER INFORMATION CONTACT).
FOR FURTHER INFORMATION CONTACT: Jeffrey Trunzo, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5111,
[[Page 24312]]
Silver Spring, MD 20993-0002, 301-796-2029, email:
<a href="/cdn-cgi/l/email-protection#eba18e8d8d998e92c5bf999e859184ab8d8f8ac5838398c58c849d"><span class="__cf_email__" data-cfemail="3b715e5d5d495e42156f494e5541547b5d5f5a15535348155c544d">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
When enacted in 1938, the Federal Food, Drug, and Cosmetic Act
(FD&C Act) required that ``new drugs'' (21 U.S.C. 321(p)) be approved
for safety by FDA before they could legally be sold in interstate
commerce. Between 1938 and 1962, if a drug obtained approval, FDA
considered drugs that were IRS (see 21 CFR 310.6(b)(1)) to the approved
drug to be covered by that approval and allowed those IRS drugs to be
marketed without independent approval.
In 1962, Congress amended the FD&C Act to require that new drugs be
proven effective for their labeled indications, as well as safe, in
order to obtain FDA approval. This amendment also required FDA to
conduct a retrospective evaluation of the effectiveness of the drug
products that FDA had approved as safe between 1938 and 1962. FDA
contracted with the National Academy of Sciences/National Research
Council (NAS/NRC) to make an initial evaluation of the effectiveness of
over 3,400 products that had been approved only for safety between 1938
and 1962. The NAS/NRC reports for these drug products were submitted to
FDA in the late 1960s and early 1970s. The Agency reviewed and
reevaluated the reports and published its findings in Federal Register
notices. FDA's administrative implementation of the NAS/NRC reports was
called the Drug Efficacy Study Implementation (DESI). DESI covered the
approximately 3,400 products specifically reviewed by the NAS/NRC, as
well as the even larger number of IRS products that entered the market
without FDA approval.
All drugs covered by the DESI review are ``new drugs'' under the
FD&C Act. If FDA's final DESI determination classifies a drug product
as lacking substantial evidence of effectiveness for one or more
indications, that drug product and those IRS to it may no longer be
marketed for such indications and are subject to enforcement action as
unapproved new drugs. If FDA's final DESI determination classifies the
drug product as effective for one or more of its labeled indications,
the drug can be marketed for such indications, provided it is the
subject of an application approved for safety and effectiveness.
Sponsors of drug products that have been found to be effective for one
or more indications through the DESI process may rely on FDA's
effectiveness determinations, but typically must update their labeling
to conform to the indication(s) found to be effective by FDA and
include any additional safety information required by FDA. Those drug
products with NDAs approved before 1962 for safety therefore require
approved supplements to their original applications if one or more
indications are found to be effective under DESI; IRS drug products
require an approved NDA or ANDA, as appropriate. Furthermore, labeling
for drug products classified as effective may contain only those
indications for which the review found the product effective unless the
firm marketing the product has received an approval for the additional
indication(s).
II. Final Resolution of Hearing Requests Regarding Oral Prescription
Drugs Containing an Anticholinergic or Antispasmodic in Combination
With a Sedative, and Single-Entity Antispasmodic Drug Products, in Oral
Dosage Form Under Docket No. FDA-1975-N-0336 (Formerly 75N-0184); DESI
10837
In a Federal Register notice published on June 22, 1971 (36 FR
11875) (1971 Federal Register notice), FDA announced its evaluation of
reports received from NAS/NRC under DESI 10837, regarding
anticholinergic drug products containing the following active
ingredients: Prochlorperazine maleate and isopropamide iodide;
oxyphencyclimine hydrochloride and meprobamate; oxyphencyclimine
hydrochloride and hydroxyzine hydrochloride; tridihexethyl chloride and
meprobamate; and propantheline bromide and thiopropazate hydrochloride.
The drugs were found to be possibly effective as adjunctive therapy in
peptic ulcer and in the irritable bowel syndrome (irritable colon,
spastic colon, mucous colitis, functional gastrointestinal disorders);
functional diarrhea; drug induced diarrhea; ulcerative colitis, and
urinary bladder spasm, and urethral spasm (i.e., smooth muscle spasm).
In addition, oxyphencyclimine and meprobamate preparations were found
to be possibly effective for dysmenorrhea. These drugs were found to
lack substantial evidence of effectiveness for their other labeled
indications.
In a Federal Register notice published November 11, 1975 (40 FR
52644) (1975 Federal Register notice), the Agency explained that
several of the products listed in the 1971 Federal Register notice may
remain on the market while clinical studies were being conducted to
determine their efficacy for the indications rated as ``possibly
effective,'' because they were widely used in the treatment of peptic
ulcer disease and functional bowel syndrome and were perceived as
important and useful tools of therapy by many gastroenterologists and
general practitioners (40 FR 52644 at 52648). In addition to the
products from the 1971 Federal Register notice, the 1975 Federal
Register notice included several products, among them Librax Capsules,
NDA 12-750, containing clidinium bromide and chlordiazepoxide, now
manufactured by Bausch Health Companies, Inc. (Bausch), that had been
the subject of safety-only applications approved before 1962 and that
had not been reviewed by NAS/NRC. Librax Capsules was included in the
1975 Federal Register notice notwithstanding the Stipulation for
Dismissal in Hoffman-La Roche, Inc. v. Richardson, et. al., Civil
Action 11-73 (D.N.J. August 2, 1973), discussed below. The 1975 Federal
Register notice set forth a timetable for conducting clinical efficacy
studies for drug products subject to the notice. In a Federal Register
notice published June 20, 1978 (43 FR 26490) (1978 Federal Register
notice), FDA announced a change in its previous policy for testing and
marketing of the drugs that were subject of the November 11, 1975,
notice (e.g., Librax), including an extension of deadline for
completion of the studies for 1 year.
In a Federal Register notice published January 16, 1981(46 FR 3977)
(1981 Federal Register notice), FDA announced its evaluation of study
reports received in response to the 1975 Federal Register notice. FDA
concluded that there was a lack of substantial evidence demonstrating
the effectiveness of the drugs listed in the 1975 notice, proposed to
withdraw approval of the new drug applications, and offered an
opportunity for hearing to manufacturers of the drugs listed in the
notice, as well as to the manufacturers of IRS products.
As set forth in a Federal Register notice published July 24, 2012
(77 FR 43337) (2012 Federal Register notice), several companies
submitted timely hearing requests in response to the 1981 Federal
Register notice, but the only such request that had not been withdrawn
as of July 2012, was the request regarding Librax Capsules, filed by
Roche Laboratories, manufacturer of Librax Capsules in 1981 (77 FR
43337 at 43341). In response to the 2012 Federal Register notice,
Valeant Pharmaceuticals North America LLC (now Bausch) affirmed the
hearing request regarding Librax Capsules by letter dated August 22,
2012.
On May 23, 2016, FDA posted a Notice to Docket 1975-N-0336,
[[Page 24313]]
explaining that Librax is not subject to review under DESI because a
new drug application for Librax was approved by the Agency on September
1, 1966, and at that time the Agency determined that Librax was safe
and effective for the indications set forth in its labeling,
(consistent with the Stipulation for Dismissal in Hoffman-La Roche,
Inc. v. Richardson, et al., Civil Action 11-73 (D.N.J. August 2,
1973)). On June 2, 2016, Valeant responded by withdrawing its hearing
request.
There are no longer outstanding hearing requests pertaining to drug
products containing an anticholinergic or antispasmodic in combination
with a sedative, and single-entity antispasmodic drug products, in oral
dosage form under Docket No. FDA-1975-N-0336, DESI 10837. Shipment in
interstate commerce of any drug product identified in this docket under
DESI 10837, or any IRS product, that is not the subject of an approved
NDA or ANDA is unlawful as of the applicable date of this notice (see
DATES). Any person who wishes to determine whether a specific product
is covered by this notice should write to Jeffrey Trunzo (see FOR
FURTHER INFORMATION CONTACT). Firms should be aware that, after the
applicable date of this notice (see DATES), FDA intends to take
enforcement action without further notice against any firm that
manufactures or ships in interstate commerce any unapproved product
covered by this notice.
III. Discontinued Products
Firms must notify the Agency of certain product discontinuations in
writing under section 506C(a) of the FD&C Act (21 U.S.C. 356c) (see
<a href="https://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htm">https://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htm</a>). Some
firms may have previously discontinued manufacturing or distributing
products covered by this notice without discontinuing the listing as
required under section 510(j) of the FD&C Act (21 U.S.C. 360(j)). Other
firms may discontinue manufacturing or distributing listed products in
response to this notice. All firms are required to electronically
update the listing of their products under 510(j) of the FD&C Act to
reflect discontinuation of unapproved products covered by this notice
(21 CFR 207.57(b)). Questions on electronic drug listing updates should
be sent to <a href="/cdn-cgi/l/email-protection#711435233d22311715105f1919025f161e07"><span class="__cf_email__" data-cfemail="385d7c6a746b785e5c591650504b165f574e">[email protected]</span></a>. In addition to the required update, firms
can also notify the Agency of product discontinuation by sending a
letter, signed by the firm's chief executive officer and fully
identifying the discontinued product(s), including the product National
Drug Code (NDC) number(s), and stating that the manufacturing and/or
distribution of the product(s) have been discontinued. The letter
should be sent electronically to Jeffrey Trunzo (see FOR FURTHER
INFORMATION CONTACT). FDA plans to rely on its existing records,
including its drug listing records, the results of any future
inspections, or other available information, when it identifies
violative products for enforcement action.
IV. Reformulated Products
FDA cautions firms against reformulating products and marketing
under the same name or substantially the same name (including a new
name that contains the old name). Reformulated products marketed under
a name previously identified with a different active ingredient or
combinations of active ingredients have the potential to confuse
healthcare practitioners and harm patients.
Dated: April 20, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08740 Filed 4-22-22; 8:45 am]
BILLING CODE 4164-01-P
</pre><script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script></body>
</html>Indexed from Federal Register on April 25, 2022.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.