Mepergan Fortis: An In-Depth Look at the FDA’s Final Decision on the Controversial Pain Medication
What was the FDA’s final decision on Mepergan Fortis Capsules. How did the regulatory process unfold for this combination pain medication. What were the key findings that led to the refusal of approval for Mepergan Fortis.
The History and Regulatory Journey of Mepergan Fortis
Mepergan Fortis Capsules (MFC) is a combination drug containing meperidine hydrochloride and promethazine hydrochloride. It was developed as a medication for sedation and analgesia in patients experiencing moderate pain and apprehension, such as those in postoperative or post-trauma situations. The regulatory history of this drug is complex and spans several decades, culminating in a final decision by the U.S. Food and Drug Administration (FDA) to refuse approval of its supplemental new drug application (sNDA).
The Drug Efficacy Study Implementation (DESI) Program
The story of Mepergan Fortis begins with the 1962 amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act). These amendments required the FDA to evaluate drugs approved between 1938 and 1962 for both safety and efficacy. This retrospective review process became known as the Drug Efficacy Study Implementation (DESI) program.
In 1972, as part of the DESI program, the FDA classified Mepergan Fortis as “possibly effective” for moderate to moderately severe pain. However, the agency noted that no New Drug Application (NDA) had been approved for MFC and that additional evidence was needed to establish its effectiveness.
The Supplemental New Drug Application Process
Following the FDA’s initial assessment, Wyeth, a division of American Home Products, submitted a supplement to its approved NDA for Mepergan Injection (NDA 11-730) to include Mepergan Fortis Capsules (NDA 11-730, S-003). This move initiated a lengthy regulatory process that would ultimately determine the fate of Mepergan Fortis.
Key Dates in the Regulatory Timeline
- September 18, 1981: The FDA proposes to refuse approval of the sNDA for Mepergan Fortis
- December 31, 1984: The FDA grants Wyeth’s request for a hearing
- January 14-17, 1986: An Administrative Law Judge (ALJ) conducts a hearing on Mepergan Fortis
- December 4, 1987: The ALJ issues an Initial Decision on the sNDA
The Administrative Law Judge’s Initial Decision
The hearing conducted by Administrative Law Judge Daniel J. Davidson was a crucial turning point in the regulatory journey of Mepergan Fortis. After reviewing written testimony and documentary evidence, the ALJ issued an Initial Decision that would shape the future of the drug.
Key Findings of the ALJ’s Decision
The ALJ’s Initial Decision contained three critical findings that ultimately led to the refusal of approval for Mepergan Fortis:
- Lack of Substantial Evidence: The effectiveness of Mepergan Fortis had not been proven by substantial evidence from adequate and well-controlled clinical trials.
- Failure to Meet Combination Drug Policy: The requirements set forth in the FDA’s combination drug policy had not been satisfied.
- Classification as a New Drug: Mepergan Fortis was determined to be a “new drug” under 21 U.S.C. 321(p), subjecting it to more stringent regulatory requirements.
These findings laid the groundwork for the FDA’s final decision on Mepergan Fortis, highlighting significant deficiencies in the drug’s application and supporting evidence.
The Appeal Process and Final Decision
Following the ALJ’s Initial Decision, Wyeth exercised its right to appeal by filing exceptions to the ruling. This action initiated an appeal process that would ultimately determine the regulatory fate of Mepergan Fortis.
The FDA’s Request for Affirmation
In a recent development, the FDA requested that the current owner of the sNDA application affirm its desire to pursue the appeal of the ALJ’s Initial Decision. This request was a critical juncture in the regulatory process, as it provided an opportunity for the applicant to either continue the appeal or effectively abandon it.
When the applicant failed to affirm its desire to pursue the appeal within the specified timeframe, the FDA took a decisive step. The agency deemed the exceptions to the ALJ’s Initial Decision as withdrawn, effectively ending the appeal process.
The Final Decision by Operation of Law
With the withdrawal of the exceptions, the regulatory proceeding found itself in the same procedural position as if no exceptions had been filed at all. As a result, the ALJ’s Initial Decision became the final decision of the FDA Commissioner by operation of law.
This final decision, effective November 16, 2017, solidified the FDA’s stance on Mepergan Fortis, refusing approval of its supplemental new drug application based on the findings of the ALJ.
Implications of the FDA’s Decision on Mepergan Fortis
The FDA’s final decision to refuse approval of Mepergan Fortis has significant implications for both the pharmaceutical industry and patients. It underscores the rigorous standards that combination drugs must meet to gain regulatory approval and highlights the importance of substantial evidence in demonstrating a drug’s effectiveness.
Impact on Combination Drug Development
The case of Mepergan Fortis serves as a cautionary tale for pharmaceutical companies developing combination drugs. It emphasizes the need for:
- Robust clinical trials that provide substantial evidence of efficacy
- Adherence to the FDA’s combination drug policy
- Clear demonstration of a drug’s benefits over its individual components
These requirements ensure that only safe and effective combination drugs reach the market, protecting public health while promoting innovation in pharmaceutical development.
The Role of Regulatory Oversight in Drug Approval
The lengthy regulatory process for Mepergan Fortis illustrates the critical role that agencies like the FDA play in ensuring the safety and efficacy of medications. This oversight is essential for maintaining public trust in the pharmaceutical industry and protecting patients from potentially harmful or ineffective drugs.
Balancing Innovation and Safety
The Mepergan Fortis case highlights the delicate balance that regulatory agencies must strike between encouraging pharmaceutical innovation and maintaining rigorous safety and efficacy standards. While the denial of approval may seem like a setback, it ultimately serves to uphold the integrity of the drug approval process and ensure that only thoroughly vetted medications reach consumers.
Lessons Learned from the Mepergan Fortis Case
The regulatory journey of Mepergan Fortis offers valuable lessons for pharmaceutical companies, healthcare providers, and patients alike. It underscores the importance of:
- Conducting thorough and well-designed clinical trials
- Adhering to regulatory guidelines and policies
- Maintaining open communication with regulatory agencies throughout the approval process
- Being prepared to provide substantial evidence of a drug’s effectiveness and safety
These lessons can help guide future drug development efforts and improve the chances of successful regulatory approval for new medications.
The Future of Pain Management and Combination Drugs
While Mepergan Fortis did not receive FDA approval, the need for effective pain management solutions remains pressing. The pharmaceutical industry continues to explore new approaches to pain relief, including novel combination drugs and alternative therapies.
Emerging Trends in Pain Management
As the field of pain management evolves, several trends are shaping the development of new treatments:
- Non-opioid analgesics to address the ongoing opioid crisis
- Targeted therapies that address specific pain pathways
- Personalized medicine approaches that tailor treatments to individual patients
- Integration of digital health technologies for pain monitoring and management
These advancements hold promise for improving pain management while potentially avoiding the regulatory pitfalls encountered by drugs like Mepergan Fortis.
In conclusion, the case of Mepergan Fortis serves as a significant example of the rigorous regulatory process that governs drug approval in the United States. It highlights the FDA’s commitment to ensuring that only safe and effective medications reach the market, even when doing so requires lengthy and complex proceedings. As the pharmaceutical industry continues to innovate in the field of pain management, the lessons learned from Mepergan Fortis will undoubtedly inform future drug development and regulatory strategies.
Mepergan Fortis Capsules; Final Decision on Proposal To Refuse Approval of Supplemental New Drug Application; Availability of Final Decision
Start Preamble
Food and Drug Administration; HHS.
Notice.
The Food and Drug Administration (FDA or the Agency) is announcing that the Initial Decision of the Administrative Law Judge (ALJ), to refuse approval of the supplemental new drug application (sNDA) for Mepergan Fortis Capsules (MFC) (meperidine HCl, promethazine HCl), is the final decision of the Commissioner by operation of law. In the Initial Decision, the ALJ found that MFC had not been shown to be supported by substantial evidence consisting of adequate and well-controlled studies to be effective for sedation and analgesia in patients with concurrent moderate pain and apprehension, such as postoperative and post-trauma patients with those symptoms; that the drug did not satisfy the combination drug policy; and that it is a “new drug.
” The sNDA applicant filed exceptions to the ALJ’s Initial Decision. FDA recently requested that the current owner of the sNDA application affirm its desire to pursue the appeal of the ALJ’s Initial Decision; however, the applicant did not affirm its desire to pursue the appeal within the specified timeframe. Accordingly, FDA now deems those exceptions as withdrawn. Consequently, the proceeding is in the same procedural position as if no exceptions to the ALJ’s Initial Decision had been filed; therefore, the ALJ’s Initial Decision has become the final decision of the Commissioner by operation of law.
This final decision is effective November 16, 2017.
For access to the docket, go to https://www.regulations.gov 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, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852 between 9 a.
m. and 4 p.m., Monday through Friday. Publicly available submissions may be seen in the docket.
Start Further Info
Rachael Vieder Linowes, Office of Scientific Integrity, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 1, Rm. 4206, Silver Spring, MD 20993, 240-402-5931.
End Further Info
End Preamble
Start Supplemental Information
I. Background
In 1962, the Federal Food, Drug, and Cosmetic Act (the FD&C Act) was amended by the Drug Amendments Act of 1962, and these amendments provided that new drugs could no longer be approved unless both safety and efficacy had been established for them. As amended, the FD&C Act also required FDA to evaluate drugs approved as safe between 1938 and 1962 to determine whether such drugs were effective and to withdraw approval for any new drug application (NDA) where there was not substantial evidence of the drug’s effectiveness.
The person contesting the withdrawal of the approval had the burden of coming forward with evidence of effectiveness for the drug. FDA’s review of these pre-1962 drugs is known as the Drug Efficacy Study Implementation (DESI) program.
In a document published in the Federal Register of April 20, 1972 (37 FR 7827), after evaluating reports received from the National Academy of Sciences/National Research Council, Drug Efficacy Study Group, and other available evidence, FDA classified MFC as “possibly effective” for moderate to moderately severe pain. This document also stated that no NDA had been approved or deemed approved for MFC and that additional evidence needed to be submitted to FDA to establish MFC’s effectiveness. Thereafter, Wyeth, a division of American Home Products (Wyeth), submitted a supplement to its approved NDA 11-730 (Mepergan Injection) for MFC (NDA 11-730, S-003). In a document published in the Federal Register of September 18, 1981 (46 FR 46404), the Director of the Bureau of Drugs (now the Center for Drug Evaluation and Research) proposed to refuse approval of the sNDA and offered Wyeth the opportunity for a hearing.
Wyeth submitted its request for a hearing and, by a document published in the Federal Register of December 31, 1984 (49 FR 50788), the Office of the Commissioner granted the hearing request. Following the submission of written testimony and documentary evidence, an ALJ, Daniel J. Davidson, conducted a hearing from January 14 to 17, 1986. He issued his Initial Decision on December 4, 1987. The ALJ found that: (1) The effectiveness of MFC had not been proven by substantial evidence of adequate and well-controlled clinical trials, (2) the requirements of the combination drug policy had not been met, and (3) MFC is a new drug under 21 U.S.C. 321(p). Wyeth timely appealed the ALJ’s Initial Decision by filing exceptions with the Commissioner under 21 CFR 12.125.
On August 23, 2017, FDA sent a letter to West-Ward Pharmaceuticals Corporation (West-Ward), successor to Wyeth, to determine whether West-Ward remained interested in pursuing its appeal of the ALJ’s Initial Decision.
FDA informed the company that if it did not respond and affirm its desire to pursue its appeal by September 21, 2017, the Office of the Commissioner would conclude that West-Ward no longer wishes to pursue the appeal of the ALJ’s Initial Decision and will proceed as if the appeal has been withdrawn. The Office of the Commissioner did not receive a response from West-Ward by the given date; therefore, the Commissioner now deems the exceptions withdrawn.
II. Conclusion and Order
Given that the exceptions have been deemed withdrawn, this proceeding is now in the same procedural posture as if no exceptions had ever been filed. When parties do not file exceptions to the ALJ’s Initial Decision, and the Commissioner does not file a notice of review, the ALJ’s Initial Decision becomes the final decision of the Commissioner (see 21 CFR 12.120(e)). FDA will publish a notice in the Federal Register when an initial decision becomes the final decision of the Commissioner without appeal to or review by the Commissioner (see 21 CFR 12.
120(f)).
Therefore, the ALJ’s Initial Decision is the final decision of the Commissioner effective November 16, 2017. Pursuant to the findings in the ALJ’s Initial Decision, under section 505(d) of the FD&C Act (21 U.S.C. 355(d)) and under the authority delegated by the Secretary of Health and Human Services, the Commissioner finds that there is a lack of substantial evidence that MFC will have the effect it purports or is represented to have under the conditions of use prescribed, Start Printed Page 53508recommended, or suggested in its labeling for sedation and analgesia in patients with concurrent moderate pain and apprehension, such as postoperative and post-trauma patients with those symptoms. The Commissioner further finds that MFC does not meet the combination drug policy in 21 CFR 300.50 and that it is a “new drug” within the meaning of 21 U.S.C. 321(p). Therefore, approval of the sNDA for MFC is denied. Distribution of products subject to the ALJ’s Initial Decision in interstate commerce without an approved application is prohibited and subject to regulatory action (see, e.
g., sections 505(a) and 301(d) (21 U.S.C. 331(d)) of the FD&C Act).
The full text of the ALJ’s Initial Decision may be seen in the Dockets Management Staff and in this docket (see ADDRESSES).
Start Signature
End Signature
End Supplemental Information
[FR Doc. 2017-24806 Filed 11-15-17; 8:45 am]
BILLING CODE 4164-01-P
Memorable misfills of a retail pharmacist
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000″>Apr 16, 2007
Every pharmacist has his own horror stories that are seared into his brain. Here are some that stand out in my mind.
1. Mepergan Fortis/cephalexin: A pharmacist told me this story. She discovered that she had dispensed Mepergan Fortis (meperidine/promethazine, Wyeth) (a powerful narcotic pain reliever) instead of cephalexin 500 mg (an antibiotic). It’s easy to see how this error occurred. Both are dark red capsules. She called her husband and told him to go to the customer’s house to retrieve the Mepergan Fortis. She cried into the phone to her husband: “GO GET IT! GO GET IT!” Her voice broke as she told me the story.
5. Carbamazepine/theophylline: A local doctor told me that one of his patients was in his office “and he’s dying.” The doctor proceeded to tell me that we had dispensed carbamazepine (which treats seizures) rather than theophylline (which treats asthma). We had dispensed the drugs in the manufacturer’s original container, so the doctor knew the contents from the exposed label.
After I listened to the doctor’s tirade, I asked, “Are you serious that he’s dying?” The doctor said, “No, but he’s pretty damned mad. His asthma has been out of control for a week.” I finally asked the doctor the question that was uppermost on my mind: “Which pharmacist’s name is on the bottle?” It turned out to be my partner’s name. I told the doctor that I was not responsible for the error, so he backed off. I found out later that my partner was indeed sued.
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FORTIS | Participant of the Skolkovo project
LIMITED LIABILITY COMPANY “FORTIS”
Primary activity (OKVED)
62.01 –
Development of computer software
90 002
About the company
Fortis company (part of the GC MONOPOLY) develops scalable logistics services for the market of moving goods by road.
The main product of the company is the high-tech web platform Monopoly.online, which hosts services for solving transport logistics problems. The company strives to solve the problem of digital disruption of the logistics industry, build a real holistic ecosystem for transport companies, retailers and manufacturers of goods, implement a full-fledged sharing economy and aggregation of resources participating in the industry. To solve these problems, the company has united in one place the best IT specialists of the country with relevant competencies and extensive experience in building an effective transport business for the MONOPOLY company. The company employs 167 employees. General Director: Mikhailova Ekaterina Vladimirovna. Founders: Monopoly JSC (
The company operates in the regions
St. Petersburg
Company maturity assessment
6
CRL (company readiness level)
8
IRL (investment readiness level)
Primary activity (OKVED)
62.
01 –
Computer software development
Projects
Business model
Business to Business to Consumer (B2B2C) Business to Business (B2B)
Project maturity assessment
9
TRL (Technology readiness level)
9
MRL (Market readiness level)
9 0002 Description of the project
ensuring the process of cargo transportation.
The solution is a digital platform that combines all the services necessary for organizing cargo transportation, from cargo search to cardless fuel processing and services from a network of proven road complexes throughout Russia.
The main functionality has been implemented: searching for cargo, paying for fuel and services of road complexes, receiving payments for transportation.
The immediate goals are to close the entire customer path of the cargo carrier into an ecosystem of products.
Products
Product Description
Multiservice
MONOPOLY.
MULTISERVICE
MONOPOLY.Multiservice
Monocard
Register of Russian programs for electronic computers and databases
https://reestr.digital.gov.ru/reestr/1445121/
URL of the copyright holder’s website with information
https://multiservice99.monopoly.su /
Product type
Software
Product description
The digital logistics platform monopoly.online combines the services necessary for the organization of cargo transportation: search for cargo and carriers, payment for fuel and roadside services. The platform is designed for the efficient organization of cargo transportation, at the moment the platform provides the possibility of agreeing on an application for the transportation of goods, creating a convenient route for cargo transportation, searching for cargo taking into account the needs of the cargo carrier, and more.
Product maturity assessment
8
TRL (Technology readiness level)
9
MRL (Market readiness level)
Project team
262 people
Revenue
368 112 000 ₽
Volume of attracted investments
425 800 000 ₽
Rates growth
2022 | 2021 | 2020 | ||
|---|---|---|---|---|
| Revenue | 368 112,000 ₽+12% 9Net profit 9013 7 | -179 549 000 ₽-25% | -143 862 000 ₽+15% | -170 015 000 ₽ |
| Number | 262 +25% | 210 +26% | 167 | |
| Intellectual property | 0 0% | 0 0% | 0 |
Contact company 0002 Financial indicators
Balance sheet
Taxes
Headcount
Intellectual property
| 2023 | |
Certificate of state registration of the computer program 2023610744 MONOPOLY. | |
MULTISERVICE| 2018 | |
Certificate of state registration of the computer program 2018617451 90 002 “CARGO. VERSION 1.2″ | |
Certificate of state registration of the computer program 2018617448 “REGULATORY BUS. VERSION 1.1” | |
Certificate of state registration of the computer program 2018617406 “ROUTING UNIT. VERSION 1.0” | |
Certificate of state registration of the computer program 2018617447 “SERVICE BUS. VERSION 1.1″ | |
Certificate of state registration of the computer program 2018617450 “TARIFF CALCULATOR. VERSION 1.0” | |
Certificate of state registration of the computer program 2018617377 “INTEGRATION BLOCK. VERSION 1.1” | |
Certificate of state registration of the computer program 2018618163 “WEB PORTAL MANAGEMENT PROGRAM FOR RESOURCE OWNERS. | |
Certificate of state registration of the computer program 2018617376 “TASK CONSTRUCTOR. VERSION 1.0” | |
Certificate of state registration of the computer program 2018617449 “TICKET-SYSTEM. VERSION 1.0” | |
Certificate of state registration of the computer program 2018618033 “PROGRAM FOR MANAGEMENT OF THE WEB PORTAL OF THE TRANSPORT COMPANY. VERSION 1.4″ | |
VERSION 1.4″| 2017 | |
Certificate of state registration of the computer program 201761478 5 MONOCARD VERSION 1.0 | |
Company information
Founders
JOINT STOCK COMPANY “MONOPOLIA”
100%
MONOPOLY
0%
Share capital
10,000 ₽
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