It seems that WADA is no longer interested in developing anti-doping tests that actually detect performance enhancing drugs (PEDs); this is understandable since serious flaws in their anti-doping tests are revealed again and again. Instead, WADA apparently believes the future of anti-doping efforts lies in anti-doping agencies cooperation with pharmaceutical companies to secretly add “traceable molecules” and “trojan molecules” (“Ricco caught by secret doping molecule: WADA chief,” July 23).

In the development of that particular substance, close cooperation occurred between WADA and the pharmaceutical company Roche Pharmaceuticals so that there was a molecule placed in the substance well in advance that was always going to be able to be detected once a test was taken,” Mr Fahey said.

Wow. I wonder what is more deplorable – athletes using performance enhancing drugs OR multi-national pharmaceutical companies secretly adding traceable molecules to consumer products and intentionally hiding this ingredient by failing to disclose it on the label?

Mr Fahey said such cooperation with drug companies was the way forward in fighting drug cheats.

“There’s more and more of this occurring,” he said.

“The more cooperation the scientists can have with the drug companies in the detection of performance-enhancing drugs the greater the likelihood is they will be detected when tests are undertaken.”

I can not imagine regulatory agencies such as the FDA looking favorably upon pharmaceutical products that have undisclosed, secret ingredients which are not essential to the action of the drug. After all, the traceable molecules have absolutely no benefit to the patient.

Certainly, this will upset quite a few people; the fact that Roche Pharmaceuticals is committing resources to non-therapeutic anti-doping efforts is, at the very least, bad public relations coming only a fews weeks after abandoning HIV/AIDS research.

The privacy, legal and regulatory obstacles to WADA’s latest approach to doping detection seems to make it a non-starter. FAIL!

Even if some pharmaceutical companies conspire with WADA in their anti-doping efforts, there are probably hundreds of pharmaceutical companies around the world, particularly in Southeast Asia, that would likely resist the extra expense of adding “traceable” anti-doping molecules to their products. The innumerous pharmaceutical companies have already given WADA problems with all the undetectable biogeneric and biosimilar EPO variants commercially available to athletes.

The testosterone doping test is flawed. The EPO test is flawed in more ways than one. Peptide hormones such as human growth hormone (HGH) and insulin-like growth factor (IGF-1) are currently undetectable. And this does not begin to address other current and emerging synthetic blood boosting techniques being used by cyclists.

It seems that anti-doping agencies are happy to assert that they are winning the war on doping while neglecting issues such as biogeneric/biosimilar erythropoietin (EPO) stimulating proteins (ESPs); blood oxygen carriers: perfluorocarbon emulsions (PFCEs) and hemoglobin based oxygen carriers (HBOCs); hydroxyethylstarch (HES/HAES); and before long, if not already, EPO-mimetic peptide (EMPs).

The newer blood boosting techniques like PFCEs and HBOCs do not increase hematocrit levels; so these drugs have performance enhancing effects without risk of exceeding the 50% hematocrit cutoff. Furthermore, the performance enhancing effects of PFCEs and HBOCs are instantaneous. The HES/HAES are actually plasma expanders and would dilute the hematocrit concentration.

Occasionally, the press reports on these substances e.g. when the U.S. Postal Team was caught with Activegin and subsequently admitted taking Activegin to the 1999 Tour de France prior to its ban and when Mauro Gianetti almost killed himself using PFCEs during the 1998 Tour of Romandy. (Ironically, Mauro Gianetti is the team manager who was “duped” by riders on the scandal-plagued Saunier Duval-Scott cycling team).

And while most of us just learned about a third generation version of EPO called Mircera, a “fourth-generation” version of EPO belonging to the class of drugs known as EMPs may receive FDA approval within the next 2-3 years; it is unknown whether athletes are currently experimenting with Hematide or Hemomer.

Blood oxygen carriers: perfluorocarbon emulsions (PFCEs) and hemoglobin based oxygen carriers (HBOCs)

Actovegin (Nycomed)
HemAssist (Baxter Healthcare)
Hemolink (Hemosol)
Hemopure (Biopure) *
Oxyglobin (Biopure) *
Oxycyte (Synthetic Blood International)
Oxygent (Alliance Pharmaceutical Corp)
PHER O2 (Sanguine Corp)
PHP (Curacyte)

Hemospan (Sangart) – added May 6, 2011
Polyheme (Northfield Laboratories) – added May 6, 2011

* Biopure assets were sold to OPK Biotech

Plasma expanders: hydroxyethylstarch (HES/HAES)

Dextran (B. Braun Medical)
Gentran (Baxter Healthcare)
Hespan (B. Braun Medical)
Voluven (Fresenius Kabi)

EPO-mimetic peptide (EMPs)

Hemomer (AplaGen Biopharmaceuticals)
Hematide (Affymax/Takeda Pharmaceutical)

***

Cyclists will continue to use performance enhancing drugs. They will continue to remain ahead of the anti-doping agencies. By only giving credence to official statements from WADA, AFLD, etc., one would believe this was all but impossible. But the evidence that doping continues is everywhere.

For example, here is an experpt from a post at RoadBikeReview.com regarding how doping is still possible given all the doping controls:

HGH, IGF-1 and Actovegin are pretty much the minimum that riders take. Ok…a few might just be on HGH because after all HGH converts in the liver to IGF-1. NONE of these drugs can be dectected…

[...]

Now for a one day classic they just come to controls with a 49% hematocrit. They can get there with blood doping or Dynepo use (human identical epo) After morning controls they have about an hour, and sometimes a little more, to blood dope. Units of their own blood are slammed into them with blood pumps. You can infuse a litre of packed cells in about an hour with no issue. This is at least 3 units of pure red cells. This will boost your hematocrit by at least 5% and sometimes 8-9%! The top riders then line up at the starting line with a 55-59% hematocrit!!!

After the race the extra blood is taken out, the plasma is spun off and the red cells are frozen as above. They end up with a 50% hematocrit. Alternatively they can just bleed the extra blood out of you until you are at 50%.

[...]

In grand tours you have to pass morning controls with no more than a 50% hematocrit, just like for any race, so they either take the extra blood out of you after the stage and save for re-infusion after morning controls, or they simply jack you with IV saline and volume expanders like Hespan right before morning controls so your hematocrit is diluted to 49-50%. You still have the same O2 carrying capacity that you had at say 56% …the blood is just diluted down. This extra fluid also comes in handy in the stage.

If you blood dope for any length of time you must supplement with very tiny doses of epo and only via the IV route. Blood doping shuts down your own red cell production so you will have next to zero retics (immature red cells) in you …and if control sees this they will know you are blood doping.

Is WADA really winning the war against doping in sports?

Athletes are using various “biosimilar” EPO agents for which WADA has not yet developed a detection method. WADA’s ballyhooed test for the previously undetectable Mircera (pegylated EPO) was an admission that the already flawed existing EPO test was unable to detect variants of EPO; the announcement of the new CERA (Mircera) test at the 2008 Tour de France was considered a major victory.

There are also dozens of “copycat” or “biosimilar” versions of EPO. These are variants of EPO that are produced by different methods or exist as slightly different biological forms of EPO e.g. darbepoetin alfa, epoetin alfa, epoetin beta, epoetin gamma, epoetin delta, epoetin epsilon, epoetin zeta, epoetin theta, epoetin kappa, epoetin omega. The existence of biosimilar versions of EPO is a major problem for drug testers (“Concerns over Olympic drug test,” July 21).

Because the medicine has been so successful financially, companies in India, China and Cuba have developed drugs that do a similar job in the body, but have a slightly different molecular fingerprint. These cheap versions of EPO, often called biosimilars, can be easily bought over the internet.

[...]

“There are now a number of compounds that bind to the EPO receptor, and there is no single test for them, you can order it here over the internet and it will be delivered to you here in the UK or in Germany; Chinese-made doping substances” [according to Professor Werner Franke].

Some scientists who track and monitor the development of copycat EPO drugs say there could be up to 80 different versions now being manufactured in different parts of the world.

A few biosimilar versions are available in the EU and Eastern Europe; however, a plethora of doping options are commercially available with biosimilar EPO pharmaceuticals produced around the world, particularly in Southeast Asia, several of which could be purchased inexpensively over the internet.

Abseamed (Medice Arzneimittel Pütter)
Aranesp (Amgen)
Binocrit (Sandoz)
Bioetin (Nanogenpharma) [Vietnam]
Ceriton (Rambaxy) [India]
Dynepo (Shire)
Epocim (CIMEQ) [Cuba]
Epoetin Alfa Hexal (Hexal Biotech Forschungs)
Epofer (Emcure) [India]
Epofit (INTAS Pharmaceuticals) [India]
Epogin (Chugai Pharmaceutical Company) [Japan]
Epokine (Macropharma Corporation) [Philippines]�
Eporon (Century Pharmaceuticals) [India]
Eporon (Dong-A Pharmaceutical Company) [Korea]
Eposino (Shandong Kexing) [China]
Eposino (Hindustan Bio Sciences) [India]
Epotin (Claris Lifesciences) [India]
Epotrex-NP (Novell Pharmaceutical) [Indonesia],
Epoyet (Bio Sudis) [Argentina],
Eritina (Chalver Laboratories) [Columbia]
Eritrogen (Bioprofarma) [Argentina]
Eritromax (Blausiegel ) [Brazil],
Erykine (INTAS Pharmaceuticals) [India]
Erypo (Janssen-Cilag)
Espo (Kirin Brewery Company, Pharmaceutical Division) [Japan]
Espogen (Hoffman Health) [Pakistan]
Gerepo (North China Pharmaceutical Group Corporation) [Malaysia]
Hemapo (Innogene Kalbiotech) [Singapore]
Hemax (Seignior Pharma) [Pakistan]
Hypercrit (Biogalenic) [Venezuela]
Mircera (Roche)
NeoRecormon (Roche)
PDpoetin (Pooyesh Darou Pharmaceuticals) [Iran]
Renoge (Biomedis) [Philippines]
Retacrit (Hospira/STADA) [Germany]
Shanpoietin (Shanta Biotechnics) [India]
Silapo (Bioceuticals Arzneimittel AG)
Vintor (Emcure) [India]
Wepox (Wockhardt) [India]
Zyrop (Zydus Biogenyc) [India]

I think the science director of WADA could be considered delusional in his claim that WADA is catching all users of recombinant EPO.

Dr Olivier Rabin is WADA’s science director. Is he happy that the test is catching all the drug cheats?

“I am reasonably confident, yes,” he told the BBC. “Now, it would be very presumptuous on my part to say that we are absolutely 100% sure we are going to get everyone. But I can assure you that if you were to take recombinant EPO and that would be in your urine – then, yes, we would detect it.“

Maybe the public will buy it, but the athletes already know better.

Hat tip to Trust But Verify.

WADA gave notice to cyclists competing at the 2008 Tour de France that they were now able to detect the performance enhancing drug Mircera (methoxy polyethylene glycol-epoetin beta), a third generation version of erythropoietin (EPO) belonging to the category of drugs known as Continuous Erythropoeitin Receptor Activators (CERA).

Doping experts concerned with the fairness of the doping protocols administered by WADA-accredited labs were quick to raise questions about the new CERA doping detection methods (“Larry: New CERA test, looking at Hamilton’s HBT,” July 20).

The TdF news concerning the detection of CERA has raised a lot of questions, including legal questions. How is it that AFLD can use a “secret” test, one that is not referenced in any of the WADA rules? How can we know that the lab’s test is valid? If there are no WADA rules for the test, how can the lab determine that the results of the test are sufficient to prove an AAF?

The folks at Trust But Verify (TBV) offer an excellent primer on unaccredited WADA anti-doping methods used to detect adverse analytical findings (AAFs). TBV, citing precedent from the Tyler Hamilton case, explains why it is legal for WADA-accredited labs to use “secret” and “unaccredited” testing methods in some cases.

[I]t is not necessary for WADA to approve a lab method before the method can be used to prove an AAF.

The panel also ruled that a WADA lab CAN use an unaccredited test method to prove an AAF, so long as the lab can prove two things. First, the lab must prove that the unaccredited test method was conducted “in accordance with the scientific community’s practices and procedures.” Second, the lab must prove that it “satisfied itself as to the validity of the [unaccredited] method before using it.” If the lab can satisfy this two-pronged burden of proof, then (according to the Hamilton decision) the lab gets the benefit of the presumption under WADA Code 3.2.1. If the lab cannot satisfy this burden, then the lab method in question cannot be used, and the AAF against the athlete must be dismissed.

The reasoning in the Hamilton case was based on the panel’s assumption that sometimes WADA labs must use unaccredited test methods. New forms of doping arise all the time, but the formal lab accreditation process is relatively slow (the method at issue in the Hamilton case was not formally validated until more than a year after the lab’s finding of the Hamilton AAF). If labs are going to detect new performance-enhancing drugs (PEDs), they may have to do so with new (and thus unaccredited) test methods. But since accreditation is an important step in making sure that test methods are “fit for purpose”, the panel reasoned that the validity of unaccredited test methods must be defended by the lab and ultimately ruled upon by the arbitration panel.

This means that AFLD may still be required to scientifically validate the new CERA test in the cases of Miguel Beltran, Moises Duenas Nevado, Riccardo Ricco and any other cyclists who accused of allegedly using Mirecera during the 2008 Tour de France.

Mircera is a third generation version of erythropoietin manufactured by pharmaceutical giant Hoffman-LaRoche that has been called “Super EPO.” The big news at the Tour is not that another cyclist was caught doping, it is that a cyclist was caught using a performance enhancing drug that was widely considered “undetectable.” The quick withdrawal of the entire Saunier Duval team from the Tour supports speculation that Mircera was the team’s secret weapon (“Riccardo Riccò tests positive; Saunier Duval team withdraws from Tour de France,” July 17).

Recent rumors in the sport had suggested that some riders were using an undetectable new oxygen-enhancing drug widely thought to be Roche’s Micera. The existence of a test for CERA was not announced, but Riccò’s positive for the substance suggests that it has not escaped the attention of anti-doping officials.

WADA spokesperson Frédéric Donzé took used the opportunity to congratulate WADA on a job well-done.

“WADA is very much aware of the development of new EPOs and biosimilar EPOs in an expanding market.”

“In the case of Mircera (CERA ) thanks to the cooperation of the manufacturer of this substance (Roche) and of WADA-accredited laboratories, WADA received the molecule well in advance and was able to develop ways to detect it,” he said. “This case shows the significant work that WADA conducts in anticipating doping trends, including by closely cooperating with pharmaceutical companies at very early stages of the development of molecules or substances for therapeutic purposes to develop detection methods for anti-doping purposes.”

Mircera is an artificial form of erythropoietin (EPO) stimulators similar to Amgen’s Epogen and Aranesp. But Mircera is thought to be superior to Epogen and Aranesp due to the use of pegylation technology that provides a sustained release of erythropoiesis stimulating proteins (ESPs). PEGylated erythropoietin (PEG-EPO) results when a molecule of polyethylene glycol is attached. 

Mircera (PEG-EPO) belongs to a category of drugs called Continuous Erythropoeitin Receptor Activators or CERA because it continuously interacts with the EPO receptor producing longer lasting effects. Only 1-2 monthly injections of Mircera have similar results to three times weekly injections of Epogen. Detailed instructions on using Mircera can be found on the Internet.

Trust But Verify wonders if Ricco actually tested positive for Mircera or was simply caught with the product in his possession (during a police search of his room). TBV points to comments made by blood doping expert Professor Michael Audren to CyclingNews.com.

It’s a delayed-action EPO, which has a different molecular mass from EPO. It’s only been commercially available since the start of the year. We can tell when someone’s used it but we can’t declare them positive. In that respect it’s like Dynepo, another EPO-like product. We know that Micera was being used on the Giro, so I’m not surprised that it’s also turned up at the Tour. But I would be very surprised if they AFLD had declared Riccò positive for Micera, for the reasons I’ve just mentioned. Maybe they searched Riccò’s room and found the product itself… (emphasis added by TBV)

It would not surprise us if TBV and Professor Audren are correct; WADA is well-known for overstating their ability to effectively and reliably detect various performance enhancing drugs.