By Eric L. Foxman, Senior Scientist, HPCUS, AAHP secretary
June 4, 2018
Of all the changes implemented by the Homeopathic Pharmacopoeia Convention of the United States (HPCUS) in the past year, perhaps the most important is a new function: you can sign up to now receive email notifications of updates to the HPUS. Some of the email notifications will be quick descriptions of changes and links to the relevant web pages while others will offer more detail. You can sign up here.*
The only change on the public side of the HPUS website is minor revision of the HPCUS Procedure Manual. The revision addresses the various standing committees and makes the text consistent in format and style when describing the purposes and progress of the committees. There are no changes in the committees’ roles — just more clarity in stating those roles.
All other changes to the HPUS website are to the contents accessed only by subscribers. For instance, there are now six newly-made-official monographs: Ascorbicum acidum, Cyanocobalaminum, Hypothalamus suis, Perlargonium reniforme, Tuba uterina suis, and Uterus suis. This brings the total of number of official monographs to 1,311, which is far more than any other officially recognized homeopathic compendia.
Standards and Controls Revisions
During 2017, the HPCUS Standards and Controls Committee added quality control specifications to 49 more monographs. Now 625, or 47 percent, of monographs include QC specifications — including nearly all of the most commonly used homeopathic drug products. The S&C Committee also updated the S&C Section. (As of press time, the update is being uploaded.) It contains more than 650 reagents, including the definitions of reagents when needed and the various concentrations that are specified in different monographs. Some definitions also include instructions on preparation of the reagent, which is especially important for those that must be freshly prepared to be used in the QC lab. Last, a Heavy Metals Limit Determination test was added to the S&C Section on standardized tests that are often referred to in multiple monographs.
In September 2016, FDA published a new guidance document: Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. Based on this Guidance, the HPCUS Council on Pharmacy (CoP) reviewed the HPUS Good Manufacturing Practices for any necessary revisions. In some cases, the CoP included reminders that homeopathic drug products are not exempt from what is expected of all pharmaceutical products. For instance, FDA’s new guidance should be followed as much as applicable at facilities producing tinctures, regardless of whether the tinctures are sold to consumers or only used for further processing. The revision also addresses particular issues or topics that have been the subject of warning letters. This helps companies learn from prior FDA actions.
Additional subjects covered in the revision include:
- Control of Inventory
- Ingredients from Cell Cultures
- Ingredients from Living Organisms
- Inventory Records and Traceability
- Manufacturing Intended for Clinical Trials/Provings
- Sampling Procedures
- Small Quantity Raw Material Testing
- Storage Conditions
- Testing and Evaluation of Results
- Validation Master Plans
- Vendor/Manufacturer Audits
Two sections of the Guidelines for Manufacturing Homeopathic Medicines were also revised for alignment. One is a not-often-used section on homeopathic drug products prepared from cell cultures. The other is in a QC subsection that now includes a reminder regarding the selection of vendors and the appropriate training for company personnel who must interact with vendors to obtain proper materials and supplies.
The CoP also highly recommends that manufacturers minimize complexity and gaps that can occur in a lengthy supply chain. One way of doing this is to obtain starting materials from a source as close as possible to the original.
An additional method has been included for processing certain sarcode substances that are defined in 8.11 with the method described in 8.2.3. This is an example of the HPUS continually being adapted to help manufacturers create uniformly prepared homeopathic drug products.
Revisions Based on User Feedback
Some updates stemmed from public input. For example:
- An extra digit was removed from the assay equation for the Cicuta Virosa monograph.
- The TLC ID test for the Bryonia monograph was reworded to better describe the required sequence of bands.
- Requirements for the starting material Anacardium orientale have been changed! This is important to any company that markets a product containing this active ingredient. Their products will be mislabeled as containing an HPUS ingredient unless changes are made to the starting material. This edit came about from someone noting a big difference between the starting material required by the HPUS verses the European Pharmacopeia. The CoP delved into historic literature. The committee concluded the botanical description in the E.P. most reflected the written references most contemporary to Hahnemann’s original proving. Thus, the Board approved a change to the starting material in the HPUS monograph.
Monograph Approval Process Revisions
This new set of guidelines was developed to provide information for monograph sponsors regarding the type of clinical data that can be submitted as a part of the monograph approval process. It will help ensure that sufficient information is submitted and that the information meets the standards for review. At the same time, the guidelines will give the reviewers sufficient guidance so their deliberations are properly focused on the expected standards and do not inadvertently raise the bar too high or inappropriately drop the threshold too low. (As of press time, the update is being uploaded.)
Revisions to Attenuation Level Definitions
Over time, more than one user has asked what it means when “N/A” is indicated for monograph attenuation levels. In working on a better explanation for this term, the committee realized the need to improve the descriptions for OTC, Rx, and HPN, as well the definition of “External Use.” These explanations are all found on this web page: Table Of Alcohol Strength, Manufacturing Class And Dispensing Potencies.
- The definition for OTC and Rx attenuations now note that these homeopathic drug products are intended to have a systemic effect.
- HPN stands for Homeopathic Pharmaceutical Necessity; it allows for the transfer between homeopathic facilities of low homeopathic attenuations that can’t be labeled for sale to the public. (The HPUS Expanded Labeling Guidelines addresses how to label HPN attenuations properly.)
- The CoP changed the final category from “External Use” to “Topical Use.” Both intended use and the method of administration need to be considered for this category.Topical use is application to a body surface for localized rather than systemic effect. A number of body surfaces that go beyond what might be considered “external” are noted, but importantly, the intended therapeutic effect is limited to the region of administration to qualify as “Topical Use.” Topical dosage forms are defined in the Guidelines for Manufacturing Homeopathic Medicines. Attenuations below the listed Topical Use attenuation can be sold for topical use but would be restricted to prescription sale.
- In the context of OTC, RX or HPN, the designation “N/A” means there are No Applicable attenuation levels for that that use. However, when utilized for External or Topical Use, N/A means that the HPUS is Not Aware of any data for the safe topical use of the monographed substance as a homeopathic drug.
In response to various discussions, the CoP added many more topical dosage forms to the Guidelines for Manufacturing Homeopathic Medicines. The number of topical dosage forms has increased from five to 18.
The Toxicity and Safety Committee (T&S) prompted changes to four attenuation just since the last notice of updates was emailed in January. Since that time, the committee reviewed attenuations in six more monographs and recommended changes affecting four, which the Board approved. The changes will become official at the end of the year. Details on the four changes and future Board-approved changes will be emailed to subscribers of the Updates. The committee plans to review at least 13 more monographs during the next few months.
The CoP will soon discuss another round of revisions to the Guidelines for Manufacturing Homeopathic Medicines. These discussions will address issues affecting product testing, including intermediates and finished products.
REMINDER: The Expanded Labeling Guidelines are now official after being posted for more than two years. The document is worth reviewing. It provides information for clearly identifying the ingredient composition in homeopathic products, especially in those containing more than one active ingredient.
* Please note: email addresses will not be shared with others and will not be used for any purpose other than to provide periodic update notifications. You will not be inundated with emails from HPCUS. For instance, in January there were three emails. In the next weeks there will be another two or three emails, and with the possibility of a couple more emails before the end of the year. This service is free; signing up is independent of a subscription to the HPUS.