All:
I’m giving a talk in a month on ethical issues in biosimilars/biologics. I’ve spotted a number of ethical issues relating to best mode (sort of old news), the weird prosecution bar statute that the BPCIA has, and a few other things. But, anyone got any other things they’ve run into/thought about? I know I’m asking if you’ve found a needle in a haystack, but…
Much appreciated.
Regarding:
“Assume the patent has expired. The generic still cannot get an ANDA without access to data because, as you noted…”
With both reference product biologics and drugs, neither FDA nor any other major market regulatory agency discloses the original applications, much less bioprocessing-related supplements, so there is no authoritative guidance or access to data at all in the public domain (other than perhaps any sponsor publications and presentations, and what may be disclosed in regulatory review documents and product labeling). I don’t think even countries such as India ever publish full pharmaceutical filings, so I don’t understand seeming expectations that there is/will be biosimilar or generic drug developer access to reference product data submitted to regulatory agencies. Biosimilar approvals in the U.S. and other major markets are based on showing lack of significant differences, both analytically and clinically, not similarities or copying innovator/reference product bioprocessing, so even if you have reference product decades-old full applications, that is unlikely to help follow-on product developers all that much.
Otherwise, in terms of explicit disclosure of ‘best mode’ no longer required in the U.S., that was decided by federal courts interpreting current laws. Effective non-disclosure and obfuscation of the ‘best mode’ of an invention is perfectly legal in the U.S. [But note, I am not an IP/patent attorney].
Thanks Ron – my curiosity is aroused given your view on what ‘ethics’ means (and noting that all attornies should be keenly aware of what ethics means):
Are you any type of an attorney?
Ron, I was reading that data exclusivity as a practical matter gives the original approver 12 years exclusivity on the biologic product even if the patent is expired, invalid, or not infringed. Thus, it appears, that patent protection is largely supplanted/irrelevant, because without access, the biologic cannot really show similarity. He must instead go through the full approval process from scratch and develop his own data.
Do I understand this correctly?
I am concerned about the statement by Ron Rader:
“Regarding data exclusivity. There is no such thing as 14 year data exclusivity protection from biosimilar approval – it’s 12 years data exclusivity in US, 10 in EU. This means that no one can reference reference product BLAs, that no one can receive biosimilar approval, during the period (ignoring patents).”
I have asked him to clarify this statement and he has not. But he appears to state that one simply cannot receive bio similar approval during the period of data exclusivity, 12 in United States and 10 in the EU.
This effectively is the same thing as patent protection, is it not, but under the rubric of data protection? How is this not similar to providing statutory trade secret protection?
Ned,
Judging from Ron’s views of ‘ethics,’ I would hazard a guess that Ron is not an attorney. I have afforded his comments their due weight.
Regarding “anon” citing my implying that, ethically, a company is forced to produce and market a pharmaceutical, that this is counter to the free market – Yes, that’s the way it is. Even the most aged, lame, legacy products have their devoted fans, and and pulling a product will energize many patient and other activist types. There will always be consumers/patients, health care professionals and others that simply don’t want products withdrawn, seeing ethical problems with this. Plus, here you’d have Big (Bio)Pharma manipulating the market to maintain full monopoly – perfectly legal, expected or required by investors, etc., but any company pulling an approved product off the market is going to get slammed PR-wise and accused of unethical practices.
Regarding data exclusivity. There is no such thing as 14 year data exclusivity protection from biosimilar approval – it’s 12 years data exclusivity in US, 10 in EU. This means that no one can reference reference product BLAs, that no one can receive biosimilar approval, during the period (ignoring patents). Biosimilarity is proven by comparative analytical and clinical testing vs. the ref. product. No full BLAs are ever made public. And similarly, full NDAs for drugs are never disclosed. So one obtains approvals, whether full, biosimilar or generic drug, without access to the reference product’s submitted data/applications. Does any country disclose/publish its full (bio)pharmaceutical filings? If so, what country? This would be an incredible competitive intelligence find (but simply does not exist)!
Otherwise, it seems to be about 1.5-2 decades since U.S. patent applications legally had to include explicit or obvious reporting of the invention’s “best mode,” which usually involved citing the example, sequence, etc. actually involving the marketed product(s). Now, “best mode” and what is actually in commerce is generally never specified and well-hidden among filler examples, sequences, etc.
“Yes, that’s the way it is. ”
Not the last I checked. You are not forced to continue to do something, just because you may have done that something in the past.
People are free* to engage in business, or to not engage in business as they see fit.
Your view of “ethics” is not one recognized as valid in this country. Do not confuse “popularity” with “ethics.”
*within recognized limits which do NOT include your apparent forced servitude notions.
Rader: “Regarding data exclusivity. There is no such thing as 14 year data exclusivity protection from biosimilar approval – it’s 12 years data exclusivity in US, 10 in EU. This means that no one can reference reference product BLAs, that no one can receive biosimilar approval, during the period (ignoring patents). ”
Do I understand you correctly that no one can even attempt to prove bio-similarity during the data exclusivity period? This is quite different from a patent where one can prove it invalid or not infringed.
What are the ethics of withdrawing a much-used, but lame, old product to both prevent all biosimilar competition and force everyone to the better 2nd or even 3rd generation replacements/follow-ons/biobetter replacement most companies have by now? Do pharmaceutical companies have obligations to keep legacy products around, even if they are no longer the safest or most effective? Is it unethical to withdraw a pharmaceutical to force its users to all use a better later-generation version (from the same company)? [Note, this has happened many times before with biopharmaceuticals, including recombinant products replacing natural ones, multiple generations of blood/plasma products with improved virus inactivation replacing prior ones starting with discovery of HIV and HCV, etc.].
One thing rarely discussed is reference products companies withdrawing their legacy products to prevent any/all biosimilars, and also potentially reinforce monopoly by moving patients to company’s newer follow-on products. In the U.S., biosimilars can’t be approved unless the ref. product was approved and comparative testing done with in-date ref. product. So, if a company (e.g., Amgen) stops manufacture and withdraws US approval, say for a legacy product with lots of safety baggage for which the company already has a marketed 2nd-generation (biobetter) product (e.g., Aranesp relative to Epogen/Procrit), the company could simply abandon/withdraw its product’s (EPO) FDA approval before patents run out, and there will be no biosimilars of this ref. product in the U.S. Already, Amgen has announced halt of all EPO manufacture, claiming loads of it is in cold storage, and few could fault (although many likely will) the company if it decided EPO was just too problematic for patients, involves too much liability, and withdrew the product, forcing everyone to use Aransesp (the only other US-marketed EPO product), thus halting approvals of andy EPO biosimilars while maintaining full monopoly.
You seem to imply that a company can be forced to make something and put it on the market – that some ethical reason exists to force this activity.
Last I checked, this was still America.
That’s interesting. Let me ponder.
David, what is this bit about 14-years data exclusivity? How does one prove biosimilarity without access to that data?
Assume the patent has expired. The generic still cannot get an ANDA without access to data because, as you noted, the patent laws have eliminated the requirement putting the best mode into the patent.
There is something really flaky about all of this. The structure actually encourages the failure to disclose best mode.
Now, is that even constitutional?
Good stuff. Let me ponder. I’ve been reading a lot these last few months about this whole area, and other medical-ethical issues on the international side. One of the perks of being a professor.
Comments are closed.