The Trials and Tribulations of Assuring Ascorbic Acid Injection Availability - The Struggle Is Over!
By Ronald M. McGuff
President, McGuff Pharmaceuticals, Inc.
For those of us on the supply side who have lived it, keeping ascorbic acid injection (AAI) available to physicians has been a roller-coaster of events ever since 1998. As an unapproved drug in the US, AAI's availability to physicians has at many times been sporadic and always susceptible to regulatory changes. Even now, the ability of compounding pharmacies and outsourcing facilities to provide AAI in the future is in question.
Today, the FDA has a very restrictive policy towards compounding pharmacies and the compounded medications they create. One especially restrictive policy is known as the "Memorandum of Understanding" (MOU) between the States and FDA. When the MOU is implemented by FDA, compounding pharmacies will be restricted from selling more than thirty percent of their total sales outside their state of residence. This may be further reduced to only five percent if a state declines to sign the FDA's MOU. If you are a physician that resides in a state that does not have a compounding pharmacy that compounds sterile drugs, your ability to obtain sterile compounded drugs may be significantly impacted. The MOU applies to all compounded drugs both sterile and non-sterile. To further complicate supply, compounding pharmacies are required by FDA guidelines to only compound based on their history of receiving prescriptions. When the MOU is implemented, compounding pharmacies may not be able to immediately support out-of-state physicians.
The MOU is but one of the roller-coaster events that continue to re-shape access to compounded drugs.
A Brief History of Ascorbic Acid Injection's Tenuous Supply
Prior to October 1998, AAI supply was dependable and available to physicians. In 1998, everything changed. Steris Laboratories, Inc., the only company actively manufacturing AAI, had failed multiple FDA inspections and signed a Consent Decree of Condemnation and Permanent Injunction.(1) The FDA seized large stocks of drugs, including AAI. This decree eliminated manufactured AAI from the market without any warning to wholesalers or physicians.
This began nineteen years of roller-coaster events that led to many AAI drug shortages. Reasons for these shortages include regulatory instabilities and industry non-compliance issues. Table 1, below, identifies the most significant roller-coaster supply events of AAI.
The Role of McGuff Pharmaceuticals
In June 2006, McGuff management realized that AAI supply was in dire jeopardy due to the recently published Guidance for FDA Staff and Industry Marketed Unapproved Drugs – Marketed New Drugs Without Approved NDAs or ANDAs. In 2006 AAI was not an approved drug. The writing was on the wall; FDA declared their policy on how unapproved drugs (read AAI) would be removed from the market.
McGuff management recognized the FDA may, at any moment, stop the manufacture of AAI. Additionally, management understood the long-term regulatory risk of compounding AAI. In July 2006 Ronald M. McGuff as President of the McGuff family of companies directed all companies to immediately initiate a strategic operational and financial strategy to secure AAI from the regulatory upheaval within the compounding pharmacy market. McGuff Pharmaceuticals, Inc. was directed to apply for and receive Orphan Drug Designation and New Drug Approval (NDA) for AAI to assure its unrestricted availability to physicians and patients.
Each roller-coaster event following McGuff's 2006 decision reassured McGuff's management that its chosen course was necessary and appropriate to assure long-term, unrestricted availability of AAI.
Orphan drug and NDA approvals are difficult to achieve. This was an eleven-year process. McGuff invested heavily into the process; money, human resources, research, test method development, human clinical trials, and significant technical help from outside consultants were employed. Some of the approval milestones of this eleven-year effort are listed in Table 2, above.
McGuff Pharmaceutical's FDA approval of Ascor ® (ascorbic acid injection)11 provides the regulatory pathway for AAI availability of the manufactured drug no matter what happens to the regulatory restrictions on compounding pharmacies and outsourcing facilities. Currently, only one of the seventy-one registered Outsourcing Facilities manufactures AAI and only in 1 mL and 5 mL Glass.(12)
Further, with the FDA approval of Ascor ® (ascorbic acid injection), physicians will no longer need to write patient specific prescriptions or have restrictions on office use. Ascor ® may be ordered in the same manner as any other approved drug.
FDA approval means much more than a consistent supply of AAI. There are other advantages as well. McGuff is currently supporting nine Investigational New Drug (IND) human clinical trials using AAI. The documentation required to receive FDA IND approval will be significantly reduced by the use of Ascor ® (ascorbic acid injection) in the IND clinical trial documentation. This may potentially allow more IND clinical trials to be submitted for FDA review.
All of us at McGuff are proud of our eleven-year effort to secure the supply of ascorbic acid injection now and well into the future. We are also very proud of the knowledge, enthusiasm, and persistence our employees displayed while performing this monumental task.
Ronald M. McGuff has been actively involved in the supply of quality drugs and devices to complementary care physicians for 38 years. As owner and President/CEO of the McGuff Family of Companies, Mr. McGuff chairs the management team that crafts policy that includes corporate purpose, governance, business principles, and ethical requirements. The McGuff Family of Companies consists of one foreign and four US corporations. All corporations are family held and veteran owned. McGuff Company, Inc. and subsidiaries provide the following diverse capabilities: aseptic drug manufacturing, medical products distribution 3PL logistics, pharmacy compounded drugs and Canadian drug distribution.
1. Consent Decree of Condemnation and Permanent Injunction previously entered against Steris Laboratories, Inc. http://www.secinfo.com/ds4Px.715d.c.htm
2. Guidance on Marketed Unapproved Drugs; Compliance Policy Guide. https://www.federalregister.gov/documents/2006/06/09/E6‐9032/guidance‐on‐marketed‐unapproved‐drugs‐co mpliance‐policy‐guide‐availability
3. Multistate Outbreak of Fungal Meningitis and Other Infections – Case Count. https://www.cdc.gov/hai/outbreaks/meningitis‐map‐large.html
4. FDA draft and final guidances on compounding pharmacy were published since July 1, 2014. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm452240.htm
5. Drug Quality and Security Act. https://www.gpo.gov/fdsys/pkg/PLAW‐113publ54/pdf/PLAW‐113publ54.pdf
6. Draft Memorandum of Understanding. https://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatory Information/Pharmacy Compounding/UCM434233.pdf
7. FDA Approved Drug Products. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209112
8. Prescribing information and package insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209112s000lbl.pdf
9. Orphan Drug Designations and Approvals. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=243707
11. For complete prescribing information for Ascor® (Ascorbic Acid Injection): http://www.mcguffpharmaceuticals.com/PDF/Ascor%20Package%20Insert.pdf
12. Outsourcing facilities manufacture’s registration of drug products produced. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UC M577376.xlsx