New Guidance Documents and New Lists
On Monday, the Food and Drug Administration (FDA) released two interim guidance documents to clarify how it intends to exercise enforcement discretion with both 503A traditional compounders - click here to view - and 503B outsourcing facilities - click here to view.
These guidance documents address the agency’s current position on what APIs can be used in preparing a compound when those bulk ingredients do not meet the Drug Quality and Security Act (DQSA) provisions that require the existence of either a USP monograph or that the API be a component of an FDA approved product.
Each of these guidance documents establish four lists. For both 503A and 503B, “List 1” shows a series of APIs which were nominated and accepted for review by the FDA’s Pharmacy Compounding Advisory Committee (PCAC). Although those reviews have not been completed, FDA is essentially permitting the use of these drugs in compounding until those reviews are finished and published on a formal list by the Secretary of Health and Human Services. A second list, “List 2” shows those APIs which were nominated for review but which the agency deems unsafe at the present time. There is only one API on List 2 for 503A compounders – domperidone. No API appears on List 2 for 503B outsourcing facilities. For both 503A and 503B, FDA has created a “List 3” of nominated drugs for which they did not receive sufficient background or information in order to present them to the PCAC for review.
Stakeholders, including IACP, have been asked to review List 3 nominations and submit additional information so that the FDA can decide whether to “bump them up” to List 1 status.
Are these lists in effect? NO. These guidance documents were published in the Federal Register on Wednesday, October 28 and comments from the public about the documents themselves – and FDA’s approach to managing nominated APIs – are being accepted until December 28, 2015. Only after those comments have been received and assessed by FDA will a final guidance document be issued. At that time, the lists will go into effect. Until that time, FDA is accepting the submission of additional information for List 3 nomination through an open docket process.
When Is a USP Monograph Not a USP Monograph?
This week, the Pharmacy Compounding Advisory Committee (PCAC) met for the third time this year to review and consider 9 nominated APIs for inclusion on the permitted bulk ingredient list. During the Open Hearing session, IACP Executive Vice President David Miller presented the Academy’s concerns about how the FDA and the PCAC are interpreting the 503A provisions that permit bulk ingredients to be used whenever a USP monograph exists.
During the June 17/18 meeting of the PCAC, a representative from FDA stated that the agency does not believe that USP dietary supplement monographs meet the statutory requirements.
That directly contradicts IACP’s and its members’ interpretation of the DQSA language about USP monographs. In general, pharmacists interpret any monograph developed and published by the United States Pharmacopeial Convention (USP) to be a “USP monograph” and thereby satisfy the requirement established in §353a(b)(1)(A)(i)(I) for the use of bulk ingredients in compounding.
During the hearing, IACP requested that USP and FDA come to a clear agreement and understanding on what a monograph “is”. Following that, IACP asked that if dietary supplement monographs are not considered sufficient by the FDA, that the nomination process for the more than 260 dietary supplements listed in USP be reopened. Our presentation is in direct follow-up to a formal letter filed with the FDA’s open docket about this issue - please click here to view.
PCAC Committee Considers Nine APIs, Accepts One
As reported live from this week’s meeting, the FDA Pharmacy Compounding Advisory Committee considered nine nominated drugs for inclusion on the pending “positive” list that would permit those bulk ingredients to be used by compounders in fulfilling patient-specific prescriptions under 503A. This list is intended to include APIs which do not have a USP/NF monograph or which are not components of an FDA-approved drug product.
These drugs, some of which had USP dietary supplement monographs, were discussed and voted on.
• Domperidone - The Committee voted 8 to 3 to NOT include or permit compounding with bulk domperidone.
• Methylsulfonylmethane (MSM) - The Committee voted 10 to 1 to NOT include or permit compounding with bulk Methylsulfonylmethane.
• Curcumin – The Committee voted 6 to 4 with 1 abstention to NOT include or permit compounding with bulk curcumin.
• Germanium sesquioxide – The Committee voted 11 to 0 to NOT include or permit compounding with bulk germanium sequioxide.
• Rubidium Chloride – The Committee voted 11 to 0 to NOT include or permit compounding with bulk rubidium chloride.
• Deoxy-D-glucose (2-D glucose) - The Committee voted 11 to 0 to NOT include or permit compounding with bulk deoxy-D-glucose.
• Alanyl-L-glutamine – The Committee voted 11 to 0 to NOT include or permit compounding with bulk alanyl-L-glutamine.
• Glutaraldehyde – the Committee voted 9 to 1 to ALLOW the use of API glutaraldehyde in compounding for topical use only.
• Glycyrrhizin – the Committee voted 11 to 0 to NOT to include or permit compounding with bulk glycyrrhizin.
It's important to remember that although the PCAC voted this week, their decision is only a recommendation to the Secretary of Health and Human Services. Until those recommendations are considered by the Secretary and formally published in the Federal Register, there are no prohibitions on using these two APIs in fulfilling a compounded prescription for an individual patient. Once published, IACP and its members, as well as other stakeholders including physicians, consumers, and other pharmacy organizations, will be able to submit additional comments about the PCAC’s decision.