How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Bi­ol­yse, an On­tario-based man­u­fac­tur­er of ster­ile in­jecta­bles, forged a deal with Bo­livia last week to man­u­fac­ture up to 50 mil­lion J&J Covid-19 vac­cine dos­es, the agree­ment kicked off what will prove to be a test case for how dif­fi­cult the sys­tem of com­pul­so­ry li­cens­es is to nav­i­gate.

The first prob­lem: When Bi­ol­yse asked J&J, via a March let­ter, to li­cense its Covid-19 vac­cine, man­u­fac­ture it in Cana­da and pay 5% roy­al­ties on ship­ments to needy, low-in­come coun­tries, J&J re­ject­ed the of­fer, re­fus­ing to ne­go­ti­ate. J&J al­so did not re­spond to a re­quest for com­ment.

With an un­will­ing J&J, Bi­ol­yse then turned to the Cana­di­an gov­ern­ment to li­cense the patents un­der a pro­gram called the Cana­di­an Ac­cess to Med­i­cines Regime, which al­lows the ex­port of drugs and vac­cines to low-in­come coun­tries like Bo­livia, with the hopes of bet­ter­ing their re­spons­es to pub­lic health crises like HIV/AIDS, tu­ber­cu­lo­sis and oth­ers.

But for those drugs or vac­cines to be ex­port­ed from Cana­da, they need to be in­clud­ed in a list cre­at­ed by the Cana­di­an gov­ern­ment, known as Sched­ule 1, which is part of the coun­try’s Patent Act.

James Love

So far, Cana­da has not added Covid-19 drugs or vac­cines to that list.

“Block­ing the list­ing on Sched­ule 1 is re­al­ly bull­shit,” James Love, di­rec­tor of the NGO Knowl­edge Ecol­o­gy In­ter­na­tion­al, who’s been push­ing to in­crease ac­cess to Covid-re­lat­ed vac­cines and ther­a­peu­tics, told End­points News. “It’s bizarre that Covid-19 is not con­sid­ered a glob­al health is­sue in Cana­da.”

A spokesper­son for the Cana­di­an gov­ern­ment’s In­no­va­tion, Sci­ence and Eco­nom­ic De­vel­op­ment pro­gram ex­plained to End­points that it’s al­so not just about adding Covid-19 vac­cines to Sched­ule 1.

“It’s im­por­tant to note that adding a COVID vac­cine to Sched­ule 1 would not al­low a com­pul­so­ry li­cense for the pro­duc­tion and ex­port of these vac­cines. A com­pa­ny seek­ing au­tho­riza­tion un­der Cana­da’s Ac­cess to Med­i­cines Regime must be able to man­u­fac­ture the drug and con­duct nec­es­sary tri­als to es­tab­lish that the drug meets Cana­di­an safe­ty and ef­fi­ca­cy re­quire­ments be­fore au­tho­riza­tion would be grant­ed,” she said.

John Ful­ton

Bi­ol­yse’s EVP John Ful­ton told End­points that his com­pa­ny could re­verse en­gi­neer the J&J vac­cine from a cou­ple drops from a vial, but the com­pa­ny would need J&J’s co­op­er­a­tion to run a tri­al and it will need ad­di­tion­al gov­ern­ment funds to scale up.

And while the gov­ern­ment spokesper­son said she’s “close­ly fol­low­ing the sit­u­a­tion” be­tween Bi­ol­yse and Bo­livia, Ful­ton said the gov­ern­ment has not been straight­for­ward in ex­plain­ing how to add Covid-19 vac­cines to Sched­ule 1.

“I start­ed in­quir­ing in late Feb­ru­ary 2021 and still they won’t give me an an­swer on how to start the process,” Ful­ton said via text mes­sage. “I’ve had meet­ings with close to 30 dif­fer­ent high-lev­el of­fi­cials and no straight an­swer on how to trig­ger the ad­di­tion.”

Bi­ol­yse said in its agree­ment with Bo­livia that it should be able to pro­duce 200,000 dos­es per week, if it ob­tains the com­pul­so­ry li­cense.

But the odds of that oc­cur­ring are low, be­cause, as Ful­ton ex­plained, it will re­quire Cana­di­an gov­ern­ment of­fi­cials to go out on a limb, and “spend the po­lit­i­cal cap­i­tal and have the courage to wade in­to the geopo­lit­i­cal storm that will en­sue when they sig­nal they sup­port the loos­en­ing of IP to vac­ci­nate LMIC [low-to-mid­dle in­come coun­tries].”

Adding Covid-19 vac­cines to Sched­ule 1 al­so would open the door for Bi­ol­yse and oth­ers to make not just J&J’s vac­cine, but Pfiz­er and Mod­er­na’s mR­NA vac­cines too, which fur­ther com­pli­cates the sit­u­a­tion.

“150 dif­fer­ent things need to hap­pen for a CL [com­pul­so­ry li­cense] to be is­sued in Cana­da just on the ex­port side,” Ful­ton added. “The TRIPS waiv­er stream­lines this process on the im­porter side.”

Pfiz­er and Mod­er­na have both made clear in re­cent weeks that they are not go­ing to help any com­pa­nies try­ing to make copy­cat ver­sions of their prod­ucts, es­pe­cial­ly as they would be vy­ing for the same raw ma­te­ri­als and nec­es­sary equip­ment.

And the Cana­di­an gov­ern­ment does not seem ready to budge, at least for now.

In­stead, the spokesper­son said the coun­try will in­vest about $2.2 bil­lion over sev­en years to­wards grow­ing a vi­brant do­mes­tic bio­man­u­fac­tur­ing and life sci­ences sec­tor, while al­so pro­vid­ing $940 mil­lion in sup­port for low- and mid­dle-in­come coun­tries to ac­cess COVID-19 vac­cines, tests, and treat­ments through the WHO’s ACT-Ac­cel­er­a­tor.

So will Bi­ol­yse raise funds and move their op­er­a­tions to an­oth­er coun­try where ob­tain­ing a com­pul­so­ry li­cense and reg­u­la­to­ry clear­ance might be eas­i­er?

No, ac­cord­ing to Ful­ton, ex­plain­ing that Bi­ol­yse has the req­ui­site fa­cil­i­ty now, and adding a fill line to a new site would add be­tween 18 months and two years to the en­tire process. But he al­so thinks that ob­tain­ing a com­pul­so­ry li­cense is about more than deal­ing with Covid-19 in the short term

“I think Covid will be with us for a long time, and I hate to say it, but we have the time. What’s hap­pen­ing in In­dia could hap­pen to us in Cana­da,” Ful­ton added. “If a com­pul­so­ry li­cense sys­tem can’t work now, dur­ing a world­wide pan­dem­ic, what’s it for? What’s the use?”

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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FDA's out­side ex­perts vote in fa­vor of Fer­ring's fe­cal trans­plant for C. dif­fi­cile, set­ting the stage for Seres

FDA’s outside advisors voted in favor of Ferring Pharmaceuticals’ RBX2660, an experimental poop-based drug implant that the company says would be the first microbiota-based live biotherapeutic to receive an FDA green light.

That was a point repeatedly discussed during the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, meeting Thursday when evaluating Ferring’s fecal microbiota transplant, or FMT, for reducing the recurrence of Clostridioides difficile infection in adults who have received antibiotics. Multiple members brought up the need for a regulated product amid a landscape of unregulated FMTs already happening in clinical care.

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Richard Pazdur, FDA's OCE director (Flatiron Health via YouTube)

FDA's OCE makes the case for ac­cel­er­at­ed ap­proval rid­er in user fee reau­tho­riza­tion

Four experts from the FDA’s Oncology Center of Excellence took to the New England Journal of Medicine yesterday to make the case for not only improving the agency’s ability to expeditiously pull dangling accelerated approvals when, on the rare occasion, confirmatory trials fail, but also better building “quality and efficiency into the AA on-ramp.”

The timely perspective arrives as Congress has exactly one week left to draft, release and sign off on the reauthorized user fee deals before layoff notices will be sent to drug reviewers. That package, which is likely to hitch a ride with the continuing resolution, may or may not include several policy riders (opposed by Republicans), including one that would allow the FDA to require confirmatory trials to be underway before an AA is granted, and would improve the process by which FDA can withdraw AAs.

As­traZeneca, Mer­ck cull one Lyn­parza in­di­ca­tion in heav­i­ly pre­treat­ed ovar­i­an can­cer pa­tients

Just one day after blockbuster Lynparza got access to another indication in China, its Big Pharma owners have decided to withdraw it in certain patients after reviewing Phase III data.

The two companies that work together on Lynparza decided to recall one of the indications several weeks ago in a specific type of ovarian cancer, Lynparza’s first indication when it was first FDA-approved in 2014. Initial data showed that rates of overall survival in patients with at least three rounds of chemo before getting on the PARP inhibitor were lower than in patients with less previous chemo treatment.

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Fu­ji­film con­tin­ues CD­MO ex­pan­sion, break­ing ground on $435M UK site

Fujifilm’s CDMO arm, Fujifilm Diosynth, has been on a roll this month as the company has recently broken ground on a major project in Europe and it appears to be keeping up the momentum.

Fujifilm Diosynth announced that it has kicked off an expansion project for its microbial manufacturing facility at its campus in the town of Billingham, UK, in the northeast of England.

The 20,000 square-foot, £400 million ($435 million) expansion will add clean rooms, purification suites and a packing area along with more space for the manufacturing itself.

An­oth­er Cipla site lands a Form 483 over clean­ing is­sues and QC con­trols

A Cipla drug manufacturing site in India has once again landed in the crosshairs of FDA inspectors.

The facility in question is Cipla’s drug manufacturing facility in the village of Verna, in the state of Goa in India’s southwest. In a sign that foreign inspections might ramp up again, the FDA’s visit from Aug. 16 to Aug. 22 uncovered six observations.

The 11-page report noted that environmental monitoring at the site did not properly ensure that microbial contaminants were not making any impact in the aseptic filling areas. It also found that procedures meant to stop microbial contamination were not adequately conducted in aseptic areas of the facility.

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