Friday, August 31, 2007

08/31/07 - More on cGMPs impact


1. Health Freedom Blog Update
2. More on the GMPs

1. Vitamin Lawyer Health Freedom Blog New Posting

More News on Lobbying Congress to Divest FDA of Food Authority.

2. More on GMPs

I’ve been reading the GMPs that were issued in June. You can read my initial blog on them at: .

Meanwhile, a number of organizations have also been reviewing the new Rules and I’ve been reviewing what they are saying. AHPA (American herbal Products Association) has been part of the process from the start. Here are excerpts from a report they’ve prepared (my headings in ALL CAPS).

BACKGROUND: "…compared to the existing cGMP for conventional foods, which is expressed … in just under six thousand words, the final rule on dietary supplement cGMP will be codified in 21 CFR 111 in over sixteen thousand words."

"Publication of this final rule is the culmination of a process that was begun in 1995 with the submission to FDA of an “industry draft” by AHPA, CRN, NDMA (now CHPA), NNFA (now NPA), and UNPA. This draft was published as an advance notice of proposed rulemaking on February 6, 1997, and followed by publication of a proposed rule on March 13, 2003" The final rule was published June 22, 2007 and can be seen at:

APPLIES TO: “The rule applies to all firms that manufacture, package, label or hold dietary supplements for sale in the U.S. and Puerto Rico, with the exception of retailers who hold dietary supplements “for the sole purpose of direct retail sale to individual consumers.” The final rule notes, however, that this retailer exception does not extend to “a warehouse or other storage facility for a retailer,” or to “a warehouse or other storage facility that sells directly to individual consumers.”

STRUCTURE OF RULE: The Rule is divided into 16 parts:

“Subpart A General Provisions (*)
Subpart B Personnel
Subpart C Physical Plant and Grounds (* as Buildings and Facilities)
Subpart D Equipment and Utensils (* as Equipment)
Subpart E Requirement to Establish a Production and Process Control System (*as Production and Process Controls)
Subpart F Production and Process Control System – Requirements for Quality Control
Subpart G Production and Process Control System **
Subpart H Production and Process Control System – Requirements for the Master Manufacturing Record
Subpart I Production and Process Control System – Requirements for the Batch Production Record
Subpart J Production and Process Control System – Requirements for Laboratory Operations
Subpart K Production and Process Control System – Requirements for Manufacturing Operations
Subpart L Production and Process Control System – Requirements for Packaging and Labeling Operations
Subpart M Holding and Distributing
Subpart N Returned Dietary Supplements
Subpart O Product Complaints
Subpart P Records and Recordkeeping”

* From the Food GMPs
** “Requirements for Components, Packaging, and Labels and for Product That You Receive for Packaging or Labeling as a Dietary Supplement”

APPLIES TO SOME CAM PRACTITIONERS: "FDA also noted in the preamble to the final rule that it “would be appropriate to consider the exercise of our enforcement discretion, on a case-by-case basis, to determine whether to apply the requirements of this final rule” to health care practitioners, such as acupuncturists, herbalists, and naturopaths who are “adequately trained in their profession” and who provide supplements that they prepare in “one-on-one consultation[s].” The agency stated, however, that it is “not considering exercising our enforcement discretion with respect to practitioners who prepare batches of herbs and sell them to individual consumers without determining whether the dietary supplement is appropriate for each consumer’s needs in a one-on-one personal consultation, or those that prepare batches of a dietary supplement for which there is a known or suspected safety concern.”"

Since that’s written in bureaucratic “bass-ackwards” let’s make that clearer: IF you do individualized one-on-one counseling, the FDA does NOT expect you to meet GMPs; if you repackage ingredients without one-on-one consultations, you will be treated as a distributor and be required to meet GMPs.

I’ve also read the United Natural Products Alliance report on the GMPs. In general their analysis is similar to AHPA. Some points they note (quotes are from the FDA Rule comments):

PRODUCT COMPLAINTS: “The final rule defines product complaint…examples of product complaints are foul odor, off-taste, illness or injury, disintegration time, color variation, tablet size or size variation, under-filled container, foreign material in a DS container, improper packaging, mislabeling or DS that are super potent, sub-potent or contain the wrong ingredient or contain a drug or other contaminant (e.g., bacteria, pesticide, mycotoxin, glass, lead)…”

QUALITY: “Quality means that the dietary supplement consistently meets the established specifications for identity, purity, strength and composition and limits on contaminates and has been manufactured, packaged, labeled and held under conditions to prevent adulteration…”

GMP TRAINING: While FDA will not provide GMP training materials, “…paragraph, § 111.14(b)(2) requires you to make and keep documentation of training, including the date of training, the type of training and the persons trained.”

BATCH TESTING: “We are persuaded that as an alternative to testing each finished batch of product, we can allow for the use of a statistically sound sampling and testing program for finished batches of DS unless a manufacturer chooses to test every batch. Such a sampling and testing program is feasible when controls are implemented earlier than the final product stage in the manufacturing process. Controls include the use of a C of A from a qualified supplier for specifications other than the identity of a DI and the establishment and monitoring of in-process manufacturing controls.”

“We agree with the comments that if we reduce the requirements for testing at the finished batch stage, then it is critical that you determine whether components meet specifications. We address this issue in the following two ways: (1) Each manufacturer must confirm the identity of each component prior to use (you must test or examine DIs to verify the identity but may rely on a C of A to confirm the identity of components other than DS) and (2) Each company must confirm other required specifications for components prior to use, either by relying upon a C of A or by testing or examining the components.”

“Because of the critical importance of insuring the proper identity of DIs – they are the central defining ingredient of a DS – we are requiring each firm that uses a DI to perform its own testing or examination for identity of each DI prior to use. Firms may not rely upon a C of A provided by suppliers to determine the identity of a DI before use. … We believe that the minimum criteria that we are establishing for a C of A, together with the requirement that a firm relying on a C of A must qualify a supplier and periodically repeat that qualification process can prevent the problems that have occurred with faulty certificates in the past.”

“Under final § 111.75(a), a firm may rely upon a C of A from its supplier of a component provided that certain criteria are met which include the following: (1) The firm first qualifies the supplier by establishing the reliability of the supplier’s C of A through confirmation of the results of the supplier’s tests or examinations; (2) The C of A includes a description of the tests or examination method(s) used, limits of the tests or examinations, and actual results of the tests or examinations; (3) The firm maintains documentation of how it qualified the supplier; (4) The firm periodically reconfirms the supplier’s C of A; (5) The firm’s quality control personnel review and approve the documentation setting for the basis for qualification (and re-qualification) of any supplier.”

PRODUCT SPECIFICATIONS: “The requirement to establish specifications is not limited to when a manufacturer purports that its product possesses attributes of strength and composition on the label. One comment asks for guidance as to what constitutes an official or scientifically valid standard for specifications. We are not aware of any officially recognized standard for specifications… the manufacturer establishes the set of criteria to which a product should conform to be considered acceptable for its intended use. In general, a specification may include a list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges or other criteria for the tests described.”

COMPLIANCE NOTIFICATION: “…an unqualified statement such as ‘produced in compliance with dietary supplement current good manufacturing requirements,’ without more, could suggest the product may be safe and effective or somehow superior to other DS products that are subject to the same CGMP requirements (id.) [and] would likely be considered misleading …, but that including language clarifying to consumers that all DS must be manufactured in compliance with CGMP requirements, and that such compliance does not mean that the DS is safe or effective, may be a way to cure that unqualified statement … Thus, we are not prohibiting voluntary statements on the DS label, provided that such statements are truthful and non-misleading…”

GMP & AER: And, despite the new AER law, “We continue to strongly recommend that firms that receive product complaints, that are not ‘serious adverse events’ notify us about any illness or injury, because, for example, we may have additional expertise or data that may be helpful in investigating the complaint or determining whether the problem applies to more than one product…We encourage you to include our recommendations in the written procedures that you develop for handling product complaints.”

CONCLUSION: Your bottom line: over the next three years, as GMPs become effective first for large firms, then in 2 years for medium firms (under 500 employees) and finally in three years for small (under 20 employees) individual firms will have to manage their compliance with the requirements. The Vitamin Lawyer Consultancy will be available to help.

STANDARD SOP: Expect my revised Standard Operating Procedures (for Dietary Supplement companies and for CAM practitioners) providing for phasing in the GMP requirements, to be available in the next month or so. I’ll let you know as soon as they are ready. You can see outlines of my pre-final rule SOPs at - these will be re-organized to fit the 16 GMP categories noted above. I estimate it will take 2 – 3 hours to customize the revised formats for each operating company responsible for GMPs.

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