For the one interested in a punt... FDA decision on MSB new drug...

For the one interested in a punt... FDA decision on MSB new drug is on the 30th of SEP. DYOR | I'm holding.

"Since we are now two weeks away from the FDA announcement, I just wanted to explain why I strongly believe MSB will obtain approval. Feel free to disagree or add to this post, but if you do, please do so with facts.

In order for Ryoncil to be approved two things first need to be determined: 1) is the product safe, pure and potent, and 2) does the facility in which it is manufactured, processed, packed, or held meet standards designed to assure the product’s continued safety, purity and potency.

Part 1: Is Ryoncil safe, pure and potent?

Ryoncil is proven to be safe and pure,but the FDA questioned whether it was potent. So all we needed to do was prove “potency”to obtain product approval. Federal regulations indicated one approach to prove the product is “potent” was to demonstrate the mechanism of action (MOA). The second approach was to use clinical performance to demonstrate potency.

FDA argued it was challenging to establish the MOA for Ryoncil since it is multimodal in function. The FDA said the precise MOA cannot be reliably determined, but Mesoblast presented evidence to support the MOA is through TNFR1. Both the FDA and Mesoblast disagree on the MOA claim, so on balance we cannot rely on using the MOA to prove the product is “potent”.

Instead it came down to whether Ryoncil was clinically effective. The ODAC committee had to vote to decide if remestemcel-L is effective for treatment of SR-aGVHD in pediatric patients and they voted 9-1in favor.

https://www.fda.gov/media/140988/download

https://www.fda.gov/media/140986/download

Part 2: Does the Lonza facility in Singapore meet the regulatory standards required for approval?

i) In Mesoblast’s Preliminary Final Report released to the market on 27/08/2020 it mentions:

“Components of a finished therapeutic product approved for commercial sale or used in late-stage clinical studies must be manufactured in accordance with current international Good Manufacturing Practice and other international regulatory requirements. These regulations govern manufacturing processes and procedures(including record keeping) and the implementation and operation of quality systems to control and assure the quality of investigational products and products approved for sale.”

“Lonza and other suppliers have never produced a commercially approved cellular therapeutic product and therefore have not yet obtained the requisite regulatory authority approvals to do so.”

“Before we can begin commercial manufacture of our products for sale in the United States, we must obtain FDA regulatory approval for the product, in addition to the approval of the processes and quality systems associated with the manufacturing of such product, which requires a successful FDA inspection of the facility handling the manufacturing of our product, including Lonza’s manufacturing facilities.”

Source: Annreliminary Final Report including Appendix 4E, Release Date: 27/08/20

ii) On August 19, 2020,the FDA released the document “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency”, which highlights requirements for pre-approval inspections:

“Foreign pre-approval and for-causeinspection assignments that are not deemed mission-critical remain temporarilypostponed, while those deemed mission-critical willstill be considered for inspection on a case-by-case basis.”

“FDA’s assessment of whether an inspection is mission-critical considers many factors related to the public health benefit of U.S. patients having access to the product subject to inspection. These factors include, but are not limited to, whether the products have received breakthroughtherapy designation or regenerative medicine advanced therapy designation, orare products used to diagnose, treat, or prevent a serious disease or medicalcondition for which there is no other appropriate substitute.”

“With respect to pre-approvalinspections, FDA intends to continue using other toolsand approaches where possible, including requesting existing inspection reportsfrom other trusted foreign regulatory partners through mutual recognition andconfidentiality agreements, requesting information from applicants, andrequesting records and other information directly from facilities and other inspected entities.”

“Applications will not automaticallyreceive a complete response letter if FDA cannot conduct an inspection. Decisions regarding applications will be based on thetotality of the information available to FDA i.e. a benefit-risk assessment.”

Source: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/manufacturing-supply-chain-and-drug-and-biological-product-inspections-during-covid-19-public-health

iii) Thequality control systems at the Lonza facility in Singapore is as follows:

Weoperate local quality management systems that comply with internal policies aswell as with national and international standards and regulations (e.g. GMP,PIC/S)

• United States Food and Drug Administration (US FDA) Code of Federal Regulations (CFR) Title 21, Parts: 11, 210, 211 and 600 (where applicable)
• Eudralex - Volume 4 Good Manufacturing Practice (GMP) Guidelines
• International Council for Harmonization (ICH)

We areproud of our excellent track record of over 20 successful inspections fromvarious agencies over the past seven year without any critical observations.

Source: https://pharma.lonza.com/about/locations/tuas-singapore

In summary: It’s difficult to see anything other than FDA approval for Ryoncil."