The association just completed another successful Compliance Thru Education webinar: FDA Inspections of Homeopathic and Drug Manufacturing Facilities: An Agency View. This webinar, held on Dec. 1, was the last of four AAHP educational events hosted during 2016.
The webinar was presented by Ms. Tamera Ely, senior policy advisor from the FDA’s Office of Compliance/Office of Manufacturing Quality. Ms. Ely began by giving background information on FDA’s inspection program and protocols; she provided participants with copies of Guidance Manuals covering numerous aspects of the agency’s inspection program. Ms. Ely went on to speak of the primary focus of inspections: the determination of a firm being “in control” of its process and procedures, which “means that a firm is complying with the minimum requirements … by producing drug products that have a level of assurance as to their quality, strength, identity and purity.” Thus, one aspect an inspector will look for is “a pattern of failure on the part of the quality unit to review and approve any procedures and documentation, or if the quality unit repeatedly fails to conduct investigations and resolve discrepancies, failures, deviations or complaints that have been identified.”
Ms. Ely continued with examples the agency has found of firms being out of control with respect to the six systems FDA could review in an inspection. When an inspector finds evidence that a firm is not operating in a state of control, this can trigger advisory, administrative or judicial actions, including warning letters, import alerts, seizures or injunctions.
Ms. Ely noted stability programs must be based on testing or examination over the normal or expected period of use and in the marketed container/closure system. She pointed out there may be instances in which final product testing for an active ingredient is warranted: if a product contains an active ingredient that at certain levels might be toxic or pose a public health hazard, then finished product testing may be appropriate as it could identify a manufacturing error that could be harmful to public health.
She also addressed different types of homeopathic starting materials and the stipulations of the HPUS. Ms. Ely made clear that field inspectors have access, through her office, to the HPUS and can refer to the specific requirements for both the classes of homeopathic drug products and the specific monographs. Continuing her theme of ‘being in control,” Ms. Ely noted manufacturers should ask themselves — and be able to document their own answers — questions such as: ‘Are one’s tinctures characterized and standardized?’ ‘How is the sterility of nosodes ensured?’ ‘How does one know the source of a sarcode was healthy?’ And even ‘Have the quality of inactive ingredients been assessed?’
Going beyond considerations of specific materials, Ms. Ely turned attention to process considerations asking: ‘What steps and documentation ensure your process produces a uniform/homogeneous product?’ ‘Based on the intended use (and dosage form), how has contamination by objectionable organisms been addressed?’ And ‘Are adequate controls in place to ensure sterility for sterile dosage forms (such as ophthalmic preparations)?’
This section of the presentation finished with more than a dozen examples from warning letters during the past years that addressed the very points covered in the webinar. Some of the examples were directly related to homeopathic drug products. Other examples covered non-homeopathic products but still represented the same types of risks that could affect our industry, including not investigating failures, poorly designed validation studies, and product contamination during packaging steps. It is clear the agency holds homeopathic companies to the same standards as other drug manufacturing and packaging firms.
Ms. Ely closed the presentation with a number of reminders and resources available to the industry, including the Section 707 changes enacted under FDASIA that address the taking of photographs during inspections; these changes are much more permissive for the agency than had been the case in the past.
There were many specific questions for Ms. Ely, who answered as many as she could during a 20-minute Q&A session. A few questions required follow-up communication between the AAHP office and Ms. Tamara, and she promised to try to obtain the requested information for participants. Questions covered:
- follow-ups after an inspection,
- what prior experiences inspectors would have with homeopathic drug products,
- familiarity of inspectors with HPUS QC test requirements,
- stability requirements for homeopathic API’s/intermediates and finished products,
- compounded homeopathic drug products,
- the specific focus of inspections,
- the kinds of adulteration which are of concern to the agency.
An archive recording of the 70-minute webinar, complete with the written presentation, as well as the 11 FDA guidance and reference documents referred to during the webinar, is available on a DVD from the AAHP office. Orders can be placed via email@example.com; the cost is $299 for non-members and $209 for AAHP members. Those attending the webinar will receive a 50% discount on the price of the DVD if ordered by Jan. 15, 2017. The archive recording can be a valuable and powerful part of your employee training program and can be used to meet your statutory training requirements.