Docket Management
Docket: 03N-0059 - Pharmaceutical Current Good Manufacturing Practices for the 21st Century: A Risk-Based Approach
Comment Number: EC -2

Accepted - Volume 1

Comment Record
Commentor Dr. Paul G. King Date/Time 2003-03-01 04:34:09
Organization F.A.M.E. Systems
Category Other

Comments for FDA General
1. General Comments REVISED COMMENTS TO CORRECT TYPOGRAPHICAL AND FORRMATTING ERRORS 1. Oddly, the FDA site reference in the FR notice of 27 February 2003 is to an unsupported and unavailable link 2. Re: Science-based policies and standards Before attempting to incorporate up-to-date science, the agency first needs to address the fundamental science that the regulations presently embody but, for whatever reasons, the agency has seemingly overlooked. Specifically, I refer to the: a) ubiquitous, but ignored requirements that all samples inspected (sampled and tested) must be representative of the batch, b) requirement that statistical quality control be used to accept or reject each batch of drug product for release, c) requirement that there be statistically based in-process monitoring of all in-process steps that can effect drug product quality including uniformity assessment, and d) the use of specific identity tests when such exist to name a few of the fundamentals of good analytical science that seem to be ignored. 3. If your approaches are to be science-based, then the FDA must make certain that the science it uses is sound. Today, the science that many in the industry or paid by the industry present to the agency is, at best, based on the misapplication or incomplete application of the fundamentals of the applied science appertaining to a truly quality-based approach inspection of a batch of drug product for its key variable distributional factors (for active and active availability) that properly determine whether a given batch is, or is not, acceptable for release to the market. 4. In my mind it is less than efficient to conflict a group with conflicting imperatives. Yet, the agency is forming a key group of inspectors that are to: a) oversee PAI inspections and b) the inspection of those firms whose history indicates a need for increased oversight -- while assuring the industry that their PAI inspections will be timely and, practically, telling the public, that the other inspections will not be timely given the agency's budgetary constraints. 5. Though the agency cites resource constraints as justification for its on-going failure to meet its statutory obligation to inspect each drug manufacturer not less than bi-annually, the reality is that it is the agency's allocation of resources to programs that have no such statutory mandates but benefit industry and not the public or public safety that interferes with its meeting its statutory inspection mandate. It is, in general, not in the public interest to have more me too lifetime treatment alternatives that can be hawked to the public and fewer and fewer disease cures -- after all it is far more beneficial to the drug industry to develop a better (usually, more expensive treatment product) than a product that cure the disease. 6. In spite of the agency's avowed systems approach to inspection and its other initiatives, the track record for the industry it regulates indicates a trend away from compliance and an increasing lack of concern about the safety and efficacy of each batch of each of the products marketed. In spite of the agency's rhetoric and perhaps because of its decreasing inspectional oversight, the public is not being protected -- Bayer's actions with respect to Baycol, Schering-Plough's willful release of defective batches of inhalers, Roche's being allowed to continue to profit from the sale of Accutane even though they obtained agency approval by deliberately concealing a key report on its CNS effects are but a few of the more egregious examples that come to mind. Though the agency and the industry are quick to point to the imputed lives saved, the reality of the increasing number of members of the public that are irreparably damaged or killed is blithely attributed to the weighing of the risk against the benefit. This approach might be acceptable if those that take the risk accrued the benefit -- however, as the dollars indicate, the industry benefits, the public takes the risk, and the industry is increasingly allowed to decide what information it will disclose and when it will disclose it -- the law and the public be damned. The public's reward is to be told that damage awards need to be capped while those in the drug and healthcare industries deserve to be able to profit without any cap and with decreasing oversight. The public would be better served if the FDA simply were to start enforcing the laws that are on the books but, in the main, have gone unenforced for more than a quarter of a century. Hopefully, if the FDA truly wants to protect the public, it will change its programs in a manner that the risk currently borne by the public for the most part will be at least adjusted to the point that it is shared equally by the public and the industry. Yet there is one irony that comforts me, the current real risk that the prescription each person gets will damage or lead to the death of the person who takes it is shared by all in our society -- from the pauper to the richest and most powerful persons in the US -- only in America. None of us can tell by looking whether, or not, the “pill we take today: a) contains the labeled amount of active or b) the level of active contained will be available to us as it is supposed to be. Perhaps that is why the industry is more than happy to spend whatever it takes to make sure that each of our pills look good (using science-based statistical product appearance control) but not to spend even the minimum required by law to guarantee that each pill in each batch of those good-looking pills will meet the science-based content and content release standards mandated by 21 CFR 211.165(d) (statistical quality control). Please get back to me if you need any clarification of the comments I have made. Thank you for providing me an opportunity to comment. When you hold hearings on this approach, I hope that you will invite me to share what little I can in this matter. Respectfully submitted on 1 March 2003 as a formal comment to Docket 03N-0059 - Pharmaceutical Current Good Manufacturing Practices for the 21st Century: A Risk-Based Approach.

EC -2